Human stem cell toxicology 1st Edition James L

Sherley install download

https://textbookfull.com/product/human-stem-cell-toxicology-1st-
edition-james-l-sherley/

Download more ebook instantly today - get yours now at textbookfull.com

We believe these products will be a great fit for you. Click
the link to download now, or visit textbookfull.com
to discover even more!

Stem Cell Derived Models in Toxicology 1st Edition Mike

Clements

https://textbookfull.com/product/stem-cell-derived-models-in-
toxicology-1st-edition-mike-clements/

Human Embryonic Stem Cell Protocols 3rd Edition Kursad

Turksen (Eds.)

https://textbookfull.com/product/human-embryonic-stem-cell-
protocols-3rd-edition-kursad-turksen-eds/

Regulating Human Embryonic Stem Cell in China A

Comparative Study on Human Embryonic Stem Cell s
Patentability and Morality in US and EU 1st Edition Li
Jiang (Auth.)
https://textbookfull.com/product/regulating-human-embryonic-stem-
cell-in-china-a-comparative-study-on-human-embryonic-stem-cell-s-
patentability-and-morality-in-us-and-eu-1st-edition-li-jiang-
auth/

Stem Cell Manufacturing 1st Edition Joaquim M. S.

Cabral

https://textbookfull.com/product/stem-cell-manufacturing-1st-
edition-joaquim-m-s-cabral/
Stem Cell Research : Hope or Hype? 1st Edition Alt

https://textbookfull.com/product/stem-cell-research-hope-or-
hype-1st-edition-alt/

Stem Cell Proliferation and Differentiation 1st Edition

Thomas G. Fazzio

https://textbookfull.com/product/stem-cell-proliferation-and-
differentiation-1st-edition-thomas-g-fazzio/

Pluripotent Stem Cell Therapy for Diabetes 1st Edition

Lorenzo Piemonti

https://textbookfull.com/product/pluripotent-stem-cell-therapy-
for-diabetes-1st-edition-lorenzo-piemonti/

Global Perspectives on Stem Cell Technologies 1st

Edition Aditya Bharadwaj (Eds.)

https://textbookfull.com/product/global-perspectives-on-stem-
cell-technologies-1st-edition-aditya-bharadwaj-eds/

Stem Cell Oncology : Proceedings of the International

Stem Cell and Oncology Conference (ISCOC, 2017),
December 1-2, 2017, Medan, Indonesia First Edition
Adella
https://textbookfull.com/product/stem-cell-oncology-proceedings-
of-the-international-stem-cell-and-oncology-conference-
iscoc-2017-december-1-2-2017-medan-indonesia-first-edition-
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP001

Human Stem Cell Toxicology

 View Online

Issues in Toxicology

Series Editors:
Professor Diana Anderson, University of Bradford, UK
Dr Michael D. Waters, Michael Waters Consulting, N. Carolina, USA
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP001

Dr Timothy C. Marrs, Edentox Associates, Kent, UK

Advisor to the Board:

Professor Alok Dhawan, CSIR-Indian Institute of Toxicology Research,
Lucknow, India

Titles in the Series:

1: Hair in Toxicology: An Important Bio-Monitor
2: Male-mediated Developmental Toxicity
3: Cytochrome P450: Role in the Metabolism and Toxicity of Drugs and
other Xenobiotics
4: Bile Acids: Toxicology and Bioactivity
5: The Comet Assay in Toxicology
6: Silver in Healthcare
7: In Silico Toxicology: Principles and Applications
8: Environmental Cardiology
9: Biomarkers and Human Biomonitoring, Volume 1: Ongoing Programs
and Exposures
10: Biomarkers and Human Biomonitoring, Volume 2: Selected Biomarkers
of Current Interest
11: Hormone-Disruptive Chemical Contaminants in Food
12: Mammalian Toxicology of Insecticides
13: The Cellular Response to the Genotoxic Insult: The Question of
Threshold for Genotoxic Carcinogens
14: Toxicological Effects of Veterinary Medicinal Products in Humans:
Volume 1
15: Toxicological Effects of Veterinary Medicinal Products in Humans:
Volume 2
16: Aging and Vulnerability to Environmental Chemicals: Age-related
Disorders and their Origins in Environmental Exposures
17: Chemical Toxicity Prediction: Category Formation and Read-Across
18: The Carcinogenicity of Metals: Human Risk Through Occupational and
Environmental Exposure
19: Reducing, Refining and Replacing the Use of Animals in Toxicity Testing
20: Advances in Dermatological Sciences
21: Metabolic Profiling: Disease and Xenobiotics
22: Manganese in Health and Disease
23: Toxicology, Survival and Health Hazards of Combustion Products
24: Masked Mycotoxins in Food: Formation, Occurrence and Toxicological
Relevance
 View Online

25: Aerobiology: The Toxicology of Airborne Pathogens and Toxins

26: Chemical Warfare Toxicology, Volume 1: Fundamental Aspects
27: Chemical Warfare Toxicology, Volume 2: Management of Poisoning
28: Toxicogenomics in Predictive Carcinogenicity
29: Human Stem Cell Toxicology
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP001

How to obtain future titles on publication:

A standing order plan is available for this series. A standing order will bring
delivery of each new volume immediately on publication.

For further information please contact:

Book Sales Department, Royal Society of Chemistry, Thomas Graham House,
Science Park, Milton Road, Cambridge, CB4 0WF, UK
Telephone: þ44 (0)1223 420066, Fax: þ44 (0)1223 420247
Email: [email protected]
Visit our website at www.rsc.org/books
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP001 View Online
 View Online

Human Stem Cell Toxicology

Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP001

Edited by

James L. Sherley
Asymmetrex, LLC, Boston, MA, USA
Email: [email protected]
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP001 View Online

Issues in Toxicology No. 29

Print ISBN: 978-1-78262-421-9

PDF eISBN: 978-1-78262-678-7
EPUB eISBN: 978-1-78262-873-6
ISSN: 1757-7179

A catalogue record for this book is available from the British Library

r The Royal Society of Chemistry 2016

All rights reserved

Apart from fair dealing for the purposes of research for non-commercial purposes or for
private study, criticism or review, as permitted under the Copyright, Designs and Patents
Act 1988 and the Copyright and Related Rights Regulations 2003, this publication may not
be reproduced, stored or transmitted, in any form or by any means, without the prior
permission in writing of The Royal Society of Chemistry or the copyright owner, or in the
case of reproduction in accordance with the terms of licences issued by the Copyright
Licensing Agency in the UK, or in accordance with the terms of the licences issued by the
appropriate Reproduction Rights Organization outside the UK. Enquiries concerning
reproduction outside the terms stated here should be sent to The Royal Society of
Chemistry at the address printed on this page.

The RSC is not responsible for individual opinions expressed in this work.

The authors have sought to locate owners of all reproduced material not in their own
possession and trust that no copyrights have been inadvertently infringed.

Published by The Royal Society of Chemistry,

Thomas Graham House, Science Park, Milton Road,
Cambridge CB4 0WF, UK

Registered Charity Number 207890

For further information see our web site at www.rsc.org

Printed in the United Kingdom by CPI Group (UK) Ltd, Croydon, CR0 4YY, UK
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP007

Contents

Chapter 1 Addressing Challenges to Progress in Human Stem Cell

Toxicology Concepts and Practice 1
James L. Sherley

1.1 Filling in the Stem Cell Gap in Human Toxicology 1

1.2 Historical Impact of the Hierarchical, Anatomical,
Sub-disciplinary Structure of Toxicological Sciences 2
1.3 Human Stem Cell Toxicology as a Stem Cell Exact
Science 3
1.4 Health and Medical Applications for Human Stem
Cell Toxicological Sciences 5
1.5 Introducing the Future Diverse Impacts of Human
Stem Cell Toxicology 6
Acknowledgements 7
References 7

Chapter 2 Alternative Methods in Haematopoietic Stem Cell

Toxicology 9
Navneet Kumar Yadav, Pooja Shukla and R. K. Singh

2.1 Introduction 9
2.2 Haematopoietic Stem Cell Toxicity or
Hematotoxicity 11
2.2.1 Sources of Haematopoietic Stem Cell Toxicity 12
2.2.2 Importance of Studying Haematopoietic
Stem Cell Toxicity 13

Issues in Toxicology No. 29

Human Stem Cell Toxicology
Edited by James L. Sherley
r The Royal Society of Chemistry 2016
Published by the Royal Society of Chemistry, www.rsc.org

vii
 View Online

viii Contents

2.2.3Haematopoietic Stem Cell Toxicity in Drug

Development 14
2.3 Colonogenic Assays as Predictors of Haematopoietic
Stem Cell Toxicity 14
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP007

2.3.1 CFU-GM Colonogenic Assay 15

2.3.2 CFU-Mk Colonogenic Assay 16
2.3.3 BFU-E Colonogenic Assay 18
2.3.4 Lymphoid Lineage Based Colonogenic
Assays 18
2.4 Conclusions 21
Acknowledgements 22
References 22

Chapter 3 High-throughput Screening of Toxic Chemicals on Neural

Stem Cells 31
Kurt Farrell, Pranav Joshi, Alexander Roth, Chandrasekhar
Kothapalli and Moo-Yeal Lee

3.1 Neural Stem Cells 31

3.2 Toxic Chemicals in the Environment 32
3.3 Mechanisms of Neural Stem Cell Toxicity 33
3.3.1 Ion Channel Blocking 34
3.3.2 Drug Metabolism Effects 37
3.3.3 Oxidative Stress 40
3.3.4 DNA/RNA Denaturation 42
3.3.5 Membrane Compromise 42
3.3.6 Other Mechanisms of
Neurotoxicity 43
3.4 NSC Differentiation 43
3.5 Conventional In vitro Assays for Toxicity Screening
against Neural Stem Cells 45
3.5.1 Well Plate Assays 45
3.5.2 Cellular Microarray Assays 47
3.5.3 Microfluidic Assays 49
3.5.4 Other Assays 51
3.6 Challenges of Conventional In vitro Approaches
in Neurotoxicity Screening 51
3.7 Conclusions and Future Directions 52
Acknowledgements 53
References 53
 View Online

Contents ix

Chapter 4 The Role of Catecholamines in Stem Cell Mobilisation 64

Brı́d M. Ryan and Oscar Vidal

4.1 Introduction 64
4.2 Catecholamines 64
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP007

4.3 Catecholamines and Stem Cell Mobilisation 67

4.3.1 Endothelial Progenitor Cells 70
4.3.2 Mesenchymal Stem Cells 71
4.3.3 Catecholamines and Stem Cell Biology 72
4.4 Consequences of Catecholamine-modulating
Agents for Stem Cell Toxicity 73
4.4.1 Other Considerations 78
4.5 Concluding Comments 80
References 81

Chapter 5 Toxicological Risk Assessment – Proposed Assay Platform

Using Stem and Progenitor Cell Differentiation in
Response to Environmental Toxicants 94
John W. Ludlow, Alexander Kinev, Michael VanKanegan,
Ben Buehrer, Nick Trotta and Joydeep Basu

5.1 Introduction 94
5.1.1 Toxicity 95
5.1.2 Environmental Toxicology 95
5.1.3 Predictive Toxicology 95
5.1.4 Automated High Content Imaging and
High Throughput, or High Content,
Screening 96
5.1.5 Risk Assessment 97
5.1.6 Components of Risk Assessment 97
5.2 Environmental Toxicological Risk Assessment
Employing an Assay Platform That Uses Stem and
Progenitor Cell Differentiation 98
5.2.1 Endothelial Colony Forming Cells (ECFCs) 99
5.2.2 ECFCs are Sensitive to Low-dose Ionizing
Radiation (LDIR) 100
5.2.3 Individual ECFC Cultures Exhibit
Donor-related LDIR Responses 100
5.2.4 The Profiling of Intracellular Signal
Transduction Pathways Provides an Insight
into the Mechanism of LDIR Toxicity 101
 View Online

x Contents

5.3 Current State of ECF Platform Development 102

5.3.1 Impedance-based Analysis of ECFC Viability
after Exposure to Environmental Toxicants 102
5.3.2 ECFCs Exhibit Lot-to-lot Variability in
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP007

Toxicant Response 105

5.3.3 Development of a Novel ROS Assay Using
ECFCs 105
5.3.4 Density-dependent ROS Levels in Cultured
ECFCs 106
5.3.5 Signal Transduction Assays in Toxicant-
treated ECFCs 108
5.4 Bioanalytical Method Validation 110
5.4.1 Development of a Quantitative High
Content Imaging (QHCA) Platform Using
ECFCs 112
5.4.2 Optimize Culture Conditions for
High-throughput Screening 112
5.4.3 Initiate Translation of Assay to 384-Well
Plates 113
5.4.4 Incorporation of Automation to Increase
Throughput 114
5.4.5 Validation of the ECFC QHCA 114
5.4.6 Determining the Z 0 factor of the Cell Death
Assays Using Positive and Negative Controls 115
5.4.7 Assessing Sources of Assay Variability
Including Manual Pipetting, Plating and
Edge Effects 116
5.4.8 Determining Day-to-day Variability of EC50
for Each Assay 116
5.4.9 Determining Significant Biological
Replicate Power 117
5.4.10 Perform the High-throughput Assay Using
Compounds from the ToxCastt Phase I
Library 117
5.4.11 Incorporation of the Toxicant-induced
ECFC Differentiation Assays into the QHCA
Screen 118
5.4.12 Establish a Repository of ECFCs from
Various Donors 120
5.5 Final Thoughts 121
References 121
 View Online

Contents xi

Chapter 6 Current Developments in the Use of Human Stem Cell

Derived Cardiomyocytes to Examine Drug-induced
Cardiotoxicity 124
Varun Ahuja, Sharad Sharma and Raj Kamboj
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP007

6.1 Introduction 124

6.2 Constraints Due to Species Differences 125
6.3 Stem Cells and iPSC-CMs 127
6.4 Limitations with Stem Cells 128
6.5 Stem Cells in Cardiovascular Safety
Pharmacology 129
6.6 Disease Models Based on iPSC-CMs 135
6.7 Generation of iPSC-CMs – Considerations on
Differentiation, Maturity, Heterogeneity and
Purification Protocols 137
6.7.1 Differentiation 137
6.7.2 Maturity 138
6.7.3 Heterogeneity 138
6.7.4 Purification 138
6.8 Use of iPSC-CMs in Phenotypic Assays 139
6.9 Assay Technologies Incorporating iPSC-CMs
and hESC-CMs 140
6.9.1 Manual Patch Clamp 140
6.9.2 Automated Patch Clamp 142
6.9.3 MEA (Microelectrode Array) 142
6.10 CiPA: Comprehensive In vitro Proarrhythmia
Assay 144
6.11 Conclusion 146
References 147

Chapter 7 Pesticides and Hematopoietic Stem Cells 160

Sujata Law and Malay Chaklader

7.1 Pesticide Toxicity-induced Disorders of

Hematopoietic System 160
7.1.1 Hematopoietic System and Hematotoxic
Pesticides 160
7.1.2 Pesticide-induced Aplastic Anemia: A Rare
but Severe Hematopathology due to Stem
Cell Failure 162
7.1.3 Assessment of Hematotoxicity 166
 View Online

xii Contents

7.2 Pesticide Toxicity on Hematopoietic Stem Cells and

their Microenvironment 167
7.2.1 Oxidative Stress Induction 167
7.2.2 Apoptosis Induction 167
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP007

7.2.3 Alteration of Developmental Signaling

Pathways 168
7.3 Experimental Medicine Against Pesticide
Toxicity-induced Hematopoietic Failure 170
7.4 Future Direction 171
References 171

Chapter 8 Epigenetic Impact of Stem Cell Toxicants 178

Anup Kumar Singh, Akhilesh Singh, Rakesh Kumar Arya,
Navneet Kumar Yadav and Dipak Datta

8.1 Introduction 178

8.2 Epigenetic Regulation of Stem Cells 181
8.3 Stem Cell Toxicants as Modulators of Epigenetic
Programming 182
8.3.1 Heavy Metals 183
8.3.2 Pharmaceuticals 185
8.4 Conclusion 187
Acknowledgements 187
References 187

Chapter 9 Metakaryotic Cancer Stem Cells are Constitutively

Resistant to X-Rays and Chemotherapeutic Agents, but
Sensitive to Many Common Drugs 196
Elena V. Gostjeva, Vera V. Koledova, Liyuan Bai, Kailin C.
Duan, Tushar Kamath, Meghan Nelson, Parul Agnihotri,
Deborah J. Moshinski, Li Ping Wu, Lawrence Zukerberg,
Daniel C. Chung, Susan Tsai, Douglas B. Evans, Aoy
Tomita-Mitchell, Michael Mitchell and William G. Thilly

9.1 Introduction 197

9.1.1 Introduction to Metakaryotic Biology 197
9.2 Materials and Methods 200
9.2.1 Methods for Studies of Metakaryotic Cancer
Stem Cells In vivo and In vitro 200
9.3 Results 204
9.3.1 Observations in Tumors after Radiation
Therapy and Chemotherapy 204
9.3.2 Observations in Cell Cultures 206
 View Online

Contents xiii

9.4 Discussion 233

9.4.1 Stem Cells in Human Tumors and Tumor-
derived Cell Lines are Amitotic,
Metakaryotic Cells 233
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP007

9.4.2 Assays that Recognize and Measure the

Toxicity of Radiation and Chemicals
to Metakaryotic Stem Cells 235
9.4.3 Growth and Development of Turnover Units
in HT-29 Cultures 235
9.4.4 Metakaryotic Stem Cells are Resistant to
Doses of X-Rays and Drug Classes
Commonly in Use for Cancer
Chemotherapy 237
9.4.5 Metakaryotic Stem Cells are Sensitive to
Many Drugs in Common Use:
Verapamil, Metformin, NSAIDS
and Antibiotics 237
9.4.6 Hypotheses about Metakaryocidal
Mechanisms, e.g. Inhibition
of Mitochondrial Function 239
9.4.7 Other Potential Targets for Metakaryocides:
Genome Replication and Segregation 241
9.4.8 Translation into Clinical Practice 242
9.4.9 Potential Use of Metakaryocides in
Prevention of Cancers and Other Clonal
Diseases 244
9.4.10 Other Considerations 244
Acknowledgements 246
References 246

Chapter 10 Distributed Stem Cell Kinetotoxicity: A New Concept to

Account for the Human Carcinogenicity of Non-genotoxic
Environmental Toxicants 250
Krishnanchali Panchalingam, Minsoo Noh, Yang Hoon Huh
and James L. Sherley

10.1 Introduction 250

10.2 Results and Discussion 253
10.2.1 Development of a High-throughput Cell
Kinetics Assay for Kinetotoxicity 253
10.2.2 Use of High-throughput Screening to
Detect Benzene and Hydroquinone as
Kinetotoxic Agents 256
 View Online

xiv Contents

10.2.3Confirmation Studies for Benzene and

Hydroquinone Kinetotoxicity 262
10.2.4 Validation of Benzene and Hydroquinone
Kinetotoxicity with DSCs 265
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP007

10.2.5 Use of Microarray Analyses to Discover a

Potential Molecular Biomarker for
Kinetotoxicity 268
10.3 Conclusions and Closing Thoughts 270
10.3.1 Kinetotoxicity, An Extended Concept in
Human Stem Cell Toxicology for
Carcinogens 270
10.3.2 Development of a High-throughput Screen
for Kinetotoxic Agents 271
10.3.3 Mechanisms of Kinetotoxicity by Benzene
and Hydroquinone 272
10.3.4 The DSC Specification Problem in Human
Stem Cell Toxicology 273
10.3.5 Looking Forward 274
10.4 Materials and Methods 275
10.4.1 Cells 275
10.4.2 Chemicals 275
10.4.3 Development of the High-throughput
Microplate Assay for Kinetotoxicity 276
10.4.4 Assays for Self-renewal Kinetics Pattern
Determination 276
10.4.5 Microarray Analyses 276
Acknowledgements 276
References 277

Chapter 11 Cancer Stem Cells as Therapeutic Targets 280

Shinji Tanaka

11.1 Introduction 280

11.2 CSC Markers and Therapeutic Targets 282
11.3 Signal Transduction in CSCs and Targeted
Agents 283
11.4 Asymmetric Cell Divisions: The Dilemma of
Studies on CSCs 284
11.5 Asymmetric Cell Divisions: Visualization of
CSCs and Toxicology 286
 View Online

Contents xv

11.6 Asymmetric Cell Divisions; Potential Therapeutics

Targeting CSCs 289
11.7 Closing Remarks 291
Acknowledgements 291
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP007

References 291

Subject Index 295

Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-FP007 View Online
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00001

CHAPTER 1

Addressing Challenges to
Progress in Human Stem Cell
Toxicology Concepts
and Practice
JAMES L. SHERLEY

Asymmetrex, LLC, P.O. Box 301179, Boston, MA 02130, USA

Email: [email protected]

1.1 Filling in the Stem Cell Gap in Human

Toxicology
One way to gauge the degree of research and practice for a scientific dis-
cipline is to evaluate the number of times that, and the period of time over
which, its quoted name is found in published scholarly reports. Table 1.1
provides such data from PubMed1 and Google Scholar2 searches for the
disciplines of ‘human toxicology’, ‘reproductive toxicology’, ‘stem cell tox-
icology’ and ‘human stem cell toxicology’. For the term ‘stem cell toxicology’,
the results show vastly fewer reports that only appeared in the past several
years; and for ‘human stem cell toxicology’, even more dramatically, there
are none. The recognition of an immediate need to begin filling in the
remarkable gap in knowledge and research disclosed by this analysis was the
inspiration for Human Stem Cell Toxicology.
Human Stem Cell Toxicology was developed with the intention of igniting a
long overdue effort to set an updated, well-informed foundation for ‘human

Issues in Toxicology No. 29

Human Stem Cell Toxicology
Edited by James L. Sherley
r The Royal Society of Chemistry 2016
Published by the Royal Society of Chemistry, www.rsc.org

1
 View Online

2 Chapter 1
Table 1.1 Database search results for fields related to human stem cell toxicology.
Field Number of reports Report years (total)
1
PubMed
‘‘Human Toxicology’’ 1101 1960–2016 (56)
‘‘Reproductive Toxicology’’ 1014 1980–2016 (36)
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00001

‘‘Stem Cell Toxicology’’ 5 2015 (1)

‘‘Human Stem Cell Toxicology’’ 0 N/A
Google Scholar2
‘‘Human Toxicology’’ 25 400 1908–2016 (108)
‘‘Reproductive Toxicology’’ 24 100 1909–2016 (107)
‘‘Stem Cell Toxicology’’ 27 2010–2016 (6)
‘‘Human Stem Cell Toxicology’’ 0 N/A

stem cell toxicology’ as a subfield of human toxicology, which, based on the

earliest scholarly reports identified by Google Scholar, is more than a cen-
tury-old discipline in human science and research. Knowing that the field of
stem cell biology is at least five decades from its origins, and human tox-
icology is a century or more old, may appear to present quite a conundrum
as to why stem cell toxicology, and human stem cell toxicology in particular,
have such scant and late representation in the scientific literature. However,
there is really no puzzle at all. First, as will be the focus later in this opening
chapter, the explanation is certainly related to scientific and technical
challenges that are unique to postnatal tissue stem cells. However, there are
also important features of the history and nature of toxicological sciences
that are also likely to have played important roles in the seeming neglect of
stem cells in toxicological research.

1.2 Historical Impact of the Hierarchical,

Anatomical, Sub-disciplinary Structure of
Toxicological Sciences
In the literature search results of Table 1.1, the subfield of reproductive
toxicology has a literature representation history that closely follows its parent
field, human toxicology. This is not surprising, as the reproductive system is
just one of the many tissue and organ systems defined by specific training,
research and expertise in human toxicology. ‘Reproductive toxicology’ is
considered here, because its usage often applies to studies that might also be
considered ‘stem cell toxicology’. Generally, the stem cells of focus have been
the germinal stem cells of the ovaries and the testes. To a lesser extent, later
on, embryonic stem cells have been considered as models for reproductive
toxicology focused on environmental and iatrogenic toxicants of embryonic
and fetal development.
The hierarchical, anatomical, sub-disciplinary structure of human tox-
icologicalsciences,whichisbasedonpopulation-,tissue-,organ-,cell-,organelle-
and molecule-specific organization of toxicants and their mechanisms of
 View Online

Addressing Challenges to Progress in Human Stem Cell Toxicology Concepts and Practice 3

action, met a pedagogical impasse with tissue stem cells. Although know-
ledge of tissue stem cells and their essential roles in tissue function and
repair is long-standing, the concept of them as critical targets of toxicants
and toxic mechanisms has been largely theoretical in construct. Import-
antly, this toxicology concept has not been readily approachable experi-
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00001

mentally. Even the concept that human carcinogens may act by inducing
alterations in tissue stem cells in humans continues to be a point of con-
troversy.3 The essential problem has been the elusive physical nature of
postnatal tissue stem cells. The challenge of distinguishing them from
other tissue cell types has thwarted the science of toxicology’s critical re-
quirement for quantifying effects of toxicants on their biological targets. So,
whereas it has been possible to define and establish toxicological
disciplines specialized for human populations, human organs, human
tissues, and many specifically identifiable other human cell types (e.g.
neurons, epidermal cells, endothelial cells, etc.), the same has not been
possible for postnatal tissue stem cells.

1.3 Human Stem Cell Toxicology as a Stem Cell

Exact Science
The above specification of ‘human stem cell toxicology’ to postnatal tissue
stem cells is not a trivial reference. Instead it is a crucial aspect of this new
toxicology discipline’s foundation. One of the most problematic aspects of
the general field of stem cell biology is the inexact language for ‘stem cells’.
This problem comes in two forms, technical and conceptual. The technical
form of the language problem is an outgrowth of well-informed and well-
intended attempts to accurately denote the cellular make-up of stem cell-
containing tissue compartments and tissue cell preparations. Because there
is often no physical basis for distinguishing postnatal tissue stem cells from
local and usually more abundant lineage-committed progenitor cells, which
are their progeny, terms like ‘stem/progenitor cells’ are widely used, as in
some chapters in this book. This usage is appropriate when the typical un-
certainty about stem cell phenotypic identity is an important consideration
or qualification. However, this terminology has become so dogmatic in the
field of mammalian stem cell biology that it has led to a widely misplaced
attitude that even conceptual or theoretical usage of the term ‘stem cell’
without including progenitors is inappropriate. In marked contrast to this
scientific piety, discussions involving current ‘stem cell biomarkers’ often
completely ignore the stem/progenitor ambiguity and apply and interpret
biomarkers, which clearly identify both stem cells and progenitor cells, as
if they only identified stem cells. As biomarkers with greater specificity
for tissue stem cells become available,4–6 this problem may resolve; but
currently it is an important correction required to set the foundation of
human stem cell toxicology as an exact science with respect to its definition
of ‘stem cell’.
 View Online

4 Chapter 1

The second conceptual form of the problem is even more fundamental,

although not known to many stem cell biologists. Stem cells are often
defined as cells that can either self-renew or differentiate. However, this
definition is only applicable to three types of cells in vitro: embryonic ‘stem’
cells, induced pluripotent ‘stem’ cells, and cancer cell lines that retain the
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00001

ability to differentiate, usually into one differentiated cell type. A characteristic

property of these cells is that they do not self-renew and differentiate. When
placed under conditions that allow differentiation, whether multiple differ-
entiated cell types are produced or only one, no self-renewing cells are
maintained. All the ‘stem’ cells, in fact, undergo differentiation. Therefore,
fundamentally, these cells are not ‘stem’ cells. They are progenitor cells. Their
conditional self-renewal is not a natural state, but one enforced by their
in vitro culture conditions. Informatively, epiblast cells, the in vivo originators
of embryonic ‘stem’ cells, are also not stem cells in their natural setting, but
instead progenitor cells. They undergo differentiation to develop the embryo,
but their initial phenotype is lost in the process.
The fundamental definition of a stem cell is a cell that can self-renew
and produce differentiating cells simultaneously without loss of its stem
phenotype for the life of the tissue that it renews. This ability, which is
unique to stem cells, is called asymmetric self-renewal.7–10 In marked
contrast to progenitor cells, stem cells preserve their stem cell phenotype.
Although the mathematical form that achieves this balance continues to
be a controversial topic,7,10,11 there is no dispute regarding the preser-
vation of the stemness phenotype being an essential element of stem cell
character.12
Three types of human tissue cells have been described that meet the
fundamental asymmetric self-renewal definition for stem cells. The first two
are well-studied, postnatal tissue-specific stem cells (also called distributed
stem cells in Chapter 10) and eukaryotic cancer stem cells (Chapter 11). The
third type is a more recently discovered remarkable class of asymmetrically
self-renewing stem cells found during the development of fetal organs and
tissues, called metakaryotic stem cells (Chapter 9). In each case, these stem
cells divide to produce differentiating progeny cells while simultaneously
maintaining their stemness properties.
The newly defined discipline of human stem cell toxicology currently
encompasses research with pluripotent cell types (e.g. Chapter 6). This in-
clusion may maintain to the extent that pluripotent cells prove to be able to
produce asymmetrically self-renewing tissue-specific stem cells in large
numbers. However, the enthusiasm for such studies must always be tem-
pered by the inherent genetic and epigenetic alterations that occur when
pluripotent cell types are derived.13 By grounding human stem cell toxi-
cology as an exact stem cell science, defined by investigation of the
toxicology of human stem cells that undergo asymmetric self-renewal, the
new discipline will also encourage increased precision with these essential
concepts in stem cell biology as a whole. Many of the contributed chapters
reflect this ideal foundation.
 View Online

Addressing Challenges to Progress in Human Stem Cell Toxicology Concepts and Practice 5

1.4 Health and Medical Applications for Human

Stem Cell Toxicological Sciences
Given the ideal foundation in an exact definition for stem cells, human stem
cell toxicology has three immediate areas of application that are directly
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00001

derivative of the involvement of the three identified types of asymmetrically

self-renewing stem cells in human health and medicine. As for human
toxicology in general, the foremost application is environmental health
science. Both fetal metakaryotic stem cells and postnatal homeostatic tissue
stem cells figure prominently in this regard. Chapters in this book focus on
the importance of these cells as targets for carcinogenic toxicants, and their
respective key roles in fetal development and postnatal tissue maturation and
aging make them crucial toxicant targets for investigation and elucidation.
The second and third applications reflect a splitting of the personality of
toxicology for medicine. On the one hand, a traditional protective toxicology
pursuit – understanding and eliminating toxic drug candidates – focused
now on postnatal tissue stem cells, is an important need in drug develop-
ment. Currently, tissue stem cell-toxic drug candidates, which are highly
unsafe drugs, are detected by their induction of organ and tissue failure in
expensive preclinical animal studies or in even more costly, in both money
and human suffering, clinical trials. New, less expensive, cell culture-based
assays for detection of tissue stem cell toxicity would accelerate drug dis-
covery and greatly reduce its cost, in terms of both expense and risk to re-
search volunteers and patients. In the case of development of drugs for fetal
disorders or that might be taken during pregnancy, this application also
applies to metakaryotic stem cells. However, as will be noted below, the
biology of metakaryotic stem cells places them in a much greater state of
readiness for achieving these advances in drug development applications.
The third application, the development of anti-cancer stem cell drugs, is
the atypical face of the toxicology personality split. Instead of seeking to
prevent or avoid stem cell toxicity, in the case of new cancer stem cell therapy
paradigms, the goal is to discover drugs with cancer stem cell-specific toxi-
city. By destroying cancer stem cells, which are responsible for the asym-
metric self-renewal of tumors, drug developers hope to induce tumor
failures, much in the way that agents toxic against normal tissue stem cells
induce organ and tissue failure. Cancer stem cell therapeutics faces all the
technical problems inherent to investigations of normal postnatal tissue
stem cells. In fact, it is likely that many cancer stem cells are derived from
mutated variants of tissue stem cells.10 So, no specific quantitative bio-
markers exist, and the cells are a small fraction of total tumor cells. The
pursuit of anti-cancer stem cell drugs has the added challenge of specific
targeting to spare normal tissue cells, and in particular normal tissue stem
cells, which are likely to be targeted often by the same agents because of the
unique properties they share with cancer stem cells.
The recently discovered metakaryotic stem cells provide a new paradigm
that sets the standard for achievement by all future investigations in human
 View Online

6 Chapter 1

stem cell toxicology. Unlike postnatal tissue stem cells and previously
described eukaryotic cancer stem cells, metakaryotic stem cells, both normal
and tumor-derived, are specifically and directly identifiable and quantifiable
based on their morphology and molecular expression (Chapter 9). Because of
their unique forms of amitotic cell division and DNA replication by a
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00001

RNA:DNA hybrid intermediate that are not shared by other cell types,
metakaryotic stem cells are physically and molecularly distinctive. Given
these ideal properties, it seems very likely that many future standard analysis
paradigms in human stem cell toxicology will be developed first in investi-
gations of the toxicology of metakaryotic stem cells, both normal ones in
fetal development and cancerous ones in fetal and postnatal tumors. Whe-
ther there is a developmental lineage relationship between metakaryotic
stem cells and homeostatic postnatal tissue stem cells or eukaryotic cancer
stem cells is presently unclear. However, if such lineage connections exist,
continued investigations of metakaryotic stem cell biology and toxicology
may reduce some of the current seemingly insurmountable barriers to tox-
icological analyses of the other two human stem cell types.

1.5 Introducing the Future Diverse Impacts of

Human Stem Cell Toxicology
Beyond setting a foundation of stem cell exactness to the new field of human
stem cell toxicology and highlighting the challenges of identifying stem cell
toxicants and their mechanism of action against human stem cells specif-
ically, this inaugural volume begins the introduction to the diverse aspects
of human stem cell toxicological science, including development of new
technologies for improving stem cell toxicant detection and addressing the
problems of specific stem cell detection; investigations for toxicant targets
that impact stem cell function indirectly; and examples of the investigation
of the effects of previously well-studied human toxicants on tissue stem cells.
As might be expected, the category with the largest number of chapters
contributed (Chapters 2, 3, 5, 9, 10) provides treatments of the progress and
challenges in developing high-throughput screens for stem cell toxicants in
both environmental health science and drug development arenas. In most
cases, developing better assays with greater stem cell definition is the main
objective of these presentations; whereas for others, the main focus is an
advance in human stem cell toxicology that required innovation in assay
technology as well.
In one case, the reported advance is an integration of a new stem cell
toxicology concept with a new technological development (Chapter 10). The
new concept, ‘kinetotoxicity’, is conceptually similar to the long-standing
colony forming unit (CFU) approach to quantifying toxicant effects on
elusive human hematopoietic stem cells (HSCs; Chapters 2 and 7), but
technically distinct. The presence of stem cells is detected indirectly by their
cellular output. In the case of the CFU approach, the scored output, mor-
phologically differentiated cell colonies, provides a largely qualitative
 View Online

Addressing Challenges to Progress in Human Stem Cell Toxicology Concepts and Practice 7

assessment of stem cell number and is limited to HSCs. Kinetotoxicity is a

quantitative measure of a toxicant’s interference with stem cell asymmetric
self-renewal, a kinetics output, and a highly associated stem cell process,
immortal strand co-segregation (ISC) that can be scored molecularly. These
advances for postnatal tissue stem cells have the potential to provide the
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00001

specific and quantitative capabilities of metakaryotic stem cells.

Although stem cells are typically sequestered in access-limited micro-
anatomical niches, these are islands with weather and shores. There are
many aspects of stem cell biology besides the autonomous processes of stem
cells (i.e. metabolism, cell division, mutagenesis, etc.) that determine their
function. Human Stem Cell Toxicology includes chapters on ‘stem cell dif-
ferentiation’ (Chapter 5), catecholamine regulation of stem cell mobilization
(Chapter 4), and stem cell epigenetics as targets for stem cell toxicants
(Chapter 8). This is but a very short list of important stem cell interactions
and regulation that toxicants might disrupt to cause stem cell toxicity.
However, these few examples serve to confirm that a basic axiom of general
human toxicology also applies to human stem cell toxicology. For example,
just as some human toxicants require metabolism by the liver before being
activated to affect a different organ site, stem cell-toxic mechanisms may
involve sites of action distal to the impacted stem cells.
A corollary of the distal action axiom is that investigations of the mech-
anisms of stem cell toxicants can lead to increased understanding of the
function and regulation of one of the most elusive cell types in the body. In
keeping with this concept, some chapters in Human Stem Cell Toxicology
consider the responses of stem cells to well-studied environmental toxicants
like pesticides (Chapter 7) and even household medicines (Chapter 9). From
these inaugural contributions to establish the discipline, as well as other
chapters in this volume, it is certain that human stem cell toxicology
promises many intriguing revelations in the future that will greatly impact
human health and medicine.

Acknowledgements
I thank Professor Diana Anderson, of the University of Bradford, UK and The
Royal Society for Chemistry, for her vision of the timeliness of this volume and
her gracious invitation to me to serve as the editor for its completion. In
addition to my co-authors for their seminal contributions, I also wish to thank
the unseen members of the international human toxicology community who
expresssed genuine enthusiasm for the project and recommended ideal
authors, both of which were crucial elements in its successful completion.

References
1. http://www.ncbi.nlm.nih.gov/pubmed.
2. https://www.google.com/webhp?ei¼KgXSVuLOLcKs-QGru5-ICQ&
ved¼0EKkuCAQoAQ.
 View Online

8 Chapter 1

3. N. L. Komarova and L. Wang, Initiation of colorectal cancer: where do

the two hits hit? Cell Cycle, 2004, 3, 1558–1565.
4. M. Noh, J. L. Smith, Y. H. Huh and J. L. Sherley, A resource for dis-
covering specific and universal biomarkers for distributed stem cells,
PLoS One, 2011, 6(7), e22077, DOI: 10.1371/journal.pone.0022077.
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00001

5. Y. H. Huh, M. Noh, F. R. Burden, J. C. Chen, D. A. Winkler and

J. L. Sherley, Sparse feature selection identifies H2A.Z as a novel, pattern-
specific biomarker for asymmetrically self-renewing distributed stem
cells, Stem Cell Res., 2015, 14, 144–154.
6. J. Y. Chen, M. Miyanishi, S. K. Wang, S. Yamazaki, R. Sinha, K. S. Kao
et al., Hoxb5 marks long-term haematopoietic stem cells and reveals a
homogeneous perivascular niche, Nature, 2016, 530, 223–227, DOI:
10.1038/nature16943.
7. M. Loeffler and C. S. Potten, Stem cells and cellular pedigrees - a con-
ceptual introduction, in Stem Cells, ed. C. S. Potten, Academic Press,
London, 1997, pp. 1–27.
8. J. Sherley, Tissue stem cells, in Encyclopedia of Cancer, ed. M. Schwab,
Springer-Verlag, Berlin, Heidelberg, 2009, DOI: 10.1007/SpringerReference_
177486 2012-05-16 22:47:18 UTC.
9. J. L. Sherley, Asymmetric self-renewal: the mark of the adult stem cell, in
Stem Cell Repair and Regeneration, ed. N. A. Habib, M. Y. Gordon,
N. Levicar, L. Jiao and G. Thomas-Black, Imperial College Press, London,
2005, pp. 21–28.
10. J. L. Sherley, New cancer diagnostics and therapeutics from a 9th
‘‘hallmark of cancer’’: Symmetric self-renewal by mutated distributed
stem cells, Expert Rev. Mol. Diagn., 2013, 13, 797–810.
11. H. Clevers, STEM CELLS. What is an adult stem cell? Science, 2015, 350,
1319–1320, DOI: 10.1126/science.aad7016.
12. J. L. Sherley, Stem cell differentiation: What does it mean? Proc. Second
Joint EMBS-BMES Conf. Houston, TX, October, 2002, 1, 741–742.
13. J. L. Sherley, Accelerating progress in regenerative medicine by advancing
distributed stem cell-based normal human cell biomanufacturing, Pharm.
Anal. Acta, 2014, 5, 286, DOI: 10.4172/2153-2435.1000286.
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00009

CHAPTER 2

Alternative Methods in
Haematopoietic Stem Cell
Toxicology
NAVNEET KUMAR YADAV,*,y POOJA SHUKLAy AND
R. K. SINGH*

Hematological Facility, Division of Toxicology, CSIR-Central Drug

Research Institute, BS-10/1, Sector 10, Jankipuram Extension,
Sitapur Road, P.O. Box 173, Lucknow 226031, India
*Email: [email protected]; [email protected]

2.1 Introduction
Hematopoietic stem cells are very primitive cells localized in the bone
marrow (BM). They are pluripotent cells, having capacity for self-renewal and
differentiation to produce all kinds of blood cells (e.g. T cells, B cells, natural
killer cells, granulocytes, monocytes, erythrocytes and platelets) to perform
different functional roles in the human body.1,2 The mature blood cells have
a limited lifespan (several days to many years); thus, hematopoietic stem
cells produce a large number of bloods cell every day to replace the dying
cells and ultimately sustain the hematopoietic system of individuals
throughout their lives (Figure 2.1).3–5
The hematopoietic system is a characteristic of all vertebrates. It performs
a plethora of functions. Amongst components of the hematopoietic system,

y
Contributed equally to this chapter.

Issues in Toxicology No. 29

Human Stem Cell Toxicology
Edited by James L. Sherley
r The Royal Society of Chemistry 2016
Published by the Royal Society of Chemistry, www.rsc.org

9
 View Online

10 Chapter 2
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00009

Figure 2.1 Illustration showing hematopoietic and stromal cell differentiation.

blood stands out as an integral one. Blood, which is the prime connective
tissue, carries out many essential functions. It is the ultimate transport
system for the delivery of oxygen from the lungs to the overall body via the
aorta, and carbon dioxide from the overall body for expiration from the
lungs. Thus, blood follows a pattern of double circulation in humans. It
carries out the transportation of various nutrients, amino acids, fats and
other essential substances to different parts of the body. Blood is vital for
maintaining basal metabolism, as it helps in maintaining optimum body
temperature via thermoregulation. Blood shows a very strict pattern of flow
in the skin that results in thermoregulatory balance. In heat, the blood flow
increases and reaches 6–8 liters per minute. Cooling temperatures lead to a
decrease in blood flow in the skin to minimum levels. The blood also
maintains thermoregulatory balance in health conditions like the meno-
pause and diabetes.6 Thus, blood tends to maintain a constant body
temperature and has a homeostatic role. Such homeostatic functions of
blood make it the ultimate buffer in the body, responsible for maintaining
a pH balance. Proper pH balance is crucial for good health. In the case of
acidic pH, the ability of cells to absorb nutrients deteriorates. The normal
reference range of pH for a healthy person is 7.35 to 7.45.7 Such a narrow
reference range is executed by the blood through various acid–base balance
mechanisms. Deviation from this normal range has been associated with
disease prognosis, e.g. acidosis, formation of tumours.8 Blood is respon-
sible for the collection of harmful and unwanted materials from each part
 View Online

Alternative Methods in Haematopoietic Stem Cell Toxicology 11

of the body and their transport to the excretory organs (e.g. kidneys) where
waste products are disposed of. Blood (along with lymph) performs im-
munogenic functions. It is responsible for transportation of the com-
ponents of the immune system to locations in the body where they are
needed. To perform such important functions, blood has to possess the
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00009

potential for rapid genesis. This is evident by the fact that a healthy adult
body produces 1–3 million new blood cells per second.9 About 2.4  106 red
blood cells (RBCs) are produced each second and live for about 120 days.
White blood cells (WBCs) have a lifespan of 59 days. There are 5–10  103
leucocytes present in each cubic centimeter. Neutrophils have a lifespan of
1–4 days, but are continuously replenished. The immense cell production
capacity of the hematopoietic system is evident by the fact that in con-
ditions of low oxygen (e.g. at high altitudes), RBC production can be as high
as six times greater compared to normal oxygen conditions. With such
short lifespans and immense proliferative capacities, blood and its cell
components are very susceptible toxicity targets for chemicals that
suppress cell proliferation.
The major breakthroughs in stem cell research started with the advent
of various technological advancements, leading to quantification of stem
cell populations. Major progress was achieved with the observation that
radiation-induced injury could be protected against by intravenous trans-
plantation of normal rat BM cells.10 Other, similar observations implied that
BM consists of adult rat cells, which are capable of repopulating and re-
establishing the destroyed cells.11
It was known that BM is not the only source of haematopoietic cells and
that the spleen also plays a vital role. First, CFUs were obtained from the
spleen.12 These CFUs carried specific biomarkers and were generated by
single parental cells (from the spleen).13 The colonies so obtained were a
cocktail of myeloid and lymphoid lineages. Myeloid are erythroid, mega-
karyocytic, granulocyte, macrophage, whereas lymphoid are the T and B
cells.14 The nature, number and types of these lineage-restricted cells were
variable.15,16 All the cells of the colonies were in the quiescent stage
(Go phase of cell cycle).17,18
Altogether, various observations led to a common notion that inside the
BM of adult mammals there resides quiescent, heterogeneous, dividing,
replenishable haematopoietic cells that can be lymphoid or myeloid in their
lineage. These cells can be used whenever the organism needs to fulfil any of
the requirements of cells throughout its lifetime.18

2.2 Haematopoietic Stem Cell Toxicity or

Hematotoxicity
By definition, hematotoxicity is the effect of chemical exposures (i.e. drugs,
chemicals, pesticides and toxicants) on the hematopoietic system including
blood, its components, and blood-forming organs (Figure 2.2).19
 View Online

12 Chapter 2
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00009

Figure 2.2 Scheme showing source of hemato-toxicants and various clonogenic

assays.

2.2.1 Sources of Haematopoietic Stem Cell Toxicity

2.2.1.1 Therapeutic Drugs
Many drug and treatment regimens act by mechanisms that suppress the
proliferative potential of the haematopoietic system. This situation occurs
because many diseases and disorders are characterized by either loss or gain
of tissue generative potential. The haematopoietic toxicity of these treatment
regimens is manifested as adverse drug reactions (ADRs). These ADRs are
undesirable side effects of these drugs. Table 2.1 provides a list of well-
known drugs that are associated with induction of haematotoxicity.20–27

2.2.1.2 Disease Conditions

Coeliac disease is correlated with hematotoxicity, which is characterized
by anemia in patients. Other manifestations of coeliac disease include
thrombocytosis, thrombocythemia, leukopenia, thromboembolism, increased
bleeding tendency, IgA deficiency, splenic dysfunction and lymphoma.

2.2.1.3 Occupational Toxicants

Table 2.2 list chemicals that are known to induce hematotoxicity when
contacted.28–31

2.2.1.4 Chemotherapy
Drug treatment regimens against cancer destroy the cancer cells by
obstructing their ability to grow and divide.32 These chemotherapy drugs
 View Online

Alternative Methods in Haematopoietic Stem Cell Toxicology 13

Table 2.1 Drugs that induce hematotoxicity as an adverse drug reaction.
S. no. Drug name Therapeutic use
1. Dapsone Leprosy
2. Ziduvidine Anti-HIV
3. Paclitaxel Anti-cancer
Published on 09 August 2016 on http://pubs.rsc.org | doi:10.1039/9781782626787-00009

4. Bendamustin Anti-chronic lymphocytic leukemia (CLL)

5. Convulex Anti-epileptic
6. Ribavirin Hepatitis
7. Rifampicine Antibiotic
8. Primaquine Antimalarial

Table 2.2 Occupational toxicants causing hematotoxicity.

S. no. Chemical name Use
1. Benzene Industrial solvent for polymer production
2. Nitrocellulose Industrial solvents commonly used in furniture,
paints and automobile spray painting industries
3. Phenylhydrazine Intermediate in agriculture industry
4. Pesticides Agrochemical industry

circulate in the bloodstream and directly damage cells that are actively
growing. Because they generally divide at a higher rate than many normal
cells, cancer cells are somewhat more susceptible to the action of these
drugs. However, damage to actively dividing normal cells occurs as well, and
this damage accounts for the ADRs of these drugs, which in the haemato-
poietic system are manifested as anemia, neutropenia, thrombocytopenia,
agranulocytosis, etc.33
Doxorubicin, carboplatin, cisplatin, lenalidomide, thalidomide, clopido-
grel, cetuximab, oxaliplatin, irinotecan, capecitabine, gemicitabine, irinote-
can, topotecan, tetraplatin and vincristine are all examples of approved,
popular, prescribed anticancer drugs.34 These induce significant hemato-
toxicity as an undesired side effect. These chemotherapy drugs are circulated
throughout the body and lack ideal selectivity for only cancer cells.
Many anticancer drugs act by obstructing the proliferative capacities of the
cells. Haematopoietic cells are one of the most highly adversely affected cell
types. This adverse side effect is evident as hematotoxicity in cancer patients
undergoing chemotherapy.35 Many reports show that this hematotoxicity
becomes a limiting factor during cancer treatment. Only 53–70% of these
treatments are able to be continued to completion.36 Completion of treat-
ment according to the treatment protocol is extremely important in order to
achieve sufficient therapeutic efficacy.

2.2.2 Importance of Studying Haematopoietic Stem Cell

Toxicity
Hematotoxicity is investigated by industrial hygienists, toxicologists and
occupational physicists. Their evaluations involve the study of chemicals
Exploring the Variety of Random
Documents with Different Content
dvrBiBdoKdAot, of, poets who are rivals in dramatic or lyric contests,
| Schol. Pind. N. 4. 60, v. Casaub. Ar. Eq. 525, cf. sq. dvrBiBdoxw, fo
teach in turn or on the other side, App. Civ. 5. 19, Anth. P, 6. 236. II.
of dramatic or lyric poets, to contend for » Plotin. 782,
 142 dvriitekepyopat, Dep. to Theaet. 167 D, avribthyyous,
ews, 7, a counter-narration, Rhetor. & pr, fut. kacrpow,
=dyridiacréAAw, Hesych., Suid. dvriStxdfopat, Dep., in pl. to implead
one another, Lys. ap. Poll. 8. 5,24. dyndixdota, %, litigation, Aquila
Prov. 20. 3. dyriSixéw, fut. ow: impf. dvridicovy Lys. 104. 16, but
Wvredixour (acc. to the best Ms.) Dem. 1006, 2., 1013. 23: aor.
Hvridixnoa Dem. ap. Poll. 8. 23. To be an dvridtxos, dispute, go to
law, wept Twos Xen. Mem. 4. 4,8; of dvridicodvres Exdrepo the
parties to a suit, Plat. Legg. 948 D; absol. of the defendant,
dvride@v Ar. Nub. 776; dvr. mpds Te or mpés Tiva, to urge one’s suit
against .., Dem. 840. fin., 1030. fin., Isae. 84. 21: to join issue,
Hvrwdixovy F why .., c. acc. et inf., Lys. l.c.: to oppose, rebut,
S:aBodais Dem. 1032. 4. a , €ws, 7), =sq., Gloss. avriBicta, 7,
litigation, contention, mpés twa brép Tivos Plut. 2. 483 B. avridixos,
ov, (Sin) an opponent or adversary ina suit, Aeschin. 50. 22;
properly the defendant, Antipho 111. 41; but also the plaintiff, Lys.
109. 25; dvr. mpés riva Antipho 112. 7; of dyridimo: the parties to a
suit, Plat. Phaedr. 273 C, al.:—generally, an opponent, adversary,
Aesch. Ag. 41. avriiixrarwp, 6, the Latin Pro-dictator, J. Lyd. de
Magistr. 1. 38. dvriBvopifw, to define in turn, give a counter-
definition, Galen. dyriBtopticow, Att. tte, to countermine, Strabo 576.
dvrdioxwors, }, a doubling of the sun’s disk, J. Lyd. de Ostent. 4.
dvriBoyparifw, fo maintain opposite principles, Twi, cited from Luc.
and Greg. Nyss. dvriSopa, aros, 75, a return, recompense, Swpwv
Eust. Opusc. 312 fin, dvrBopn, 7), (5€uw) an opposed or substituted
building, Aen. Tact. 23. dvrBotdlw, to be of a contrary opinion, Plat.
Theaet. 170 D. dvriBottw, =foreg., mpés twa or Tut Polyb. 2. 56, 1.,
16. 14, 43 TIM mepi Twos Diod. 2.29; dvridoge? Strab. 110 (as
Madv. for dv 71, doger 3’). avriBotos, ov, (5éfa) of a different
opinion or sect, Luc. Hermot. 17 ; Haxn popas dvr. Id. Paras. 29.
ayriBopos, ov, (Sopa) clothed with something instead of a skin,
napvoy xAwpis dvridopoy Aemidos Anth. P. 6. 22. dvriBoots, ews, 7,
(dvrididwp) a giving in return, an exchange, Arist. Eth. N. 5. 5, 8,
Call. Fr. 221; gopriev Diod. 2. 54; alxuadwrov 12, 63; xaxav App. Civ.
1. 3; % eis tiv owmhy dvr, Ael. N. A. 5. 9 — repay quital, &Bpews
Luc. Alex. 50:—éyridociy Twos in return for .., Epigr. Gr. 822. II. at
Athens, a form by which a citizen charged with a Xevroupyia or
elapopa might call upon any other citizen, whom he thought richer
than himself, either to exchange properties, or to submit to the
charge himself, Lys. 98.9, etc.; kadciaOai tiva eis dvr. Tpinpapxias
Xen. Oec. 7,3; Kkaraords xopnyds eg dvriddcews Dem. 505.8;
moretoOae dvr. tive Dem. 50. 20; avt. én éut mapecxevacav 840.
27; cf. Isocr. wept ’Avridécews, Dem. in Phaenipp., Wolf Lept. p.
cxxiii, Béckh P. E. 2. 368, and v. dvrididqpu 11. avriBorucads, Adv. by
way of recompense, Eust. Opusc. 193. 55. GvriSoros, ov, (dyrididwp)
given in lieu of, mupds Anth. P. 9g. 165. IL. given as a remedy for,
kax@v pappaxoy avr. Ib. 10. 118. 2. as Subst., dvridoros (sc. Séats),
7, an antidote, remedy, Anth, P. 12. 13, Clem. Al. 461: in other
places the gender is uncertain, Plut. 2. 42 D, 54 8, ete. dvriBovdetw,
fo serve in turn, rots Texovat yap Svornvos boris pavTiSovdrever (for
wh dvr.) Téxvev Eur. Supp. 362. dvriSoudos, ov, instead of a slave,
neut. pl. as Adv., ravpwv yovas Bods -dyriBovda Aesch. Fr. 194. II. of
persons, being as a slave, treated as a slave, Id. Cho. 135. avri ‘0S,
ov, re-echoing’, Aesch. Pers, 121 ; Body dvridouma rut Ib. 1040.
dvripdcoopat, Att. —rropat, to Jay hold of, xapdias Themist. 357 B.
dvriSpdw, fut. -Spdow [a], to act against, to retaliate, maddy piv
dvréSpav Soph. O. C. 271, cf. Eur. Andr. 438, Antipho 126.12; dv6 dy
renovOas jfiovv 1d3° dvridpav Soph. O. C. 953; mpds ras mpdges
dy. Ib. 959. II. c. acc. pers. to repay, requite, avr. rd Kakds Ib. 1191,
cf. Plat. Crito 49 D; yevvata yap maddvres ipas dvridpay épetdopev
Eur. Supp. 1179. dvriBpopéw, to run in a contrary direction, dub. in
Luc. Astrol. 12. dvrBuoxepatve, fut. diva, to be angry in turn, M.
Anton. 6. 26. dvriBvowTéw, to entreat in turn, Twa moeiv tt Eus. V.
Const. 4. 33. dvriBwped, 4, a return-gift, recompense, Arist. Eth. N.
4. 2, 15. dvriBwpéopar, Dep. fo present in return, dvr. Tid Tie one
with a thing, Hdt. 2. 30, Plat., etc.; also, rwi re a thing ¢o one, Oeot
3€ cor t00AGy dporBas dvriSwpnoaiaro Eur. Hel. 159, cf. Plat.
Euthyphro 14.E; with 7¢ only, Arist. Eth. N. 8. 8, 6. dvribebyvupr, to
annex, e.g. a word in the corresponding clause of a sentence, Dion.
H. ad Amm. 2, p- 800. wrifndos, 6, %, a rival, adversary, Lxx (Levit.
18. 18, Sirac. 26. 6). avribnA da, to be emulous of, rival, Byz.:—
alsoin Med., 710% Clem. Al. 319. dvrilnréw, to seek one who is
seeking us, Xen. Occ. 8, 23. dvrifopat, Ion. for dvOifoua, to sit
before or opposite. avrifityos, ov, put in the opposite scale: hence
balancing, correspondent, Arist. P. A. 3. 4, 15, Plut. 2. 723 C.
avribityéw, to counterbalance, correspond, mpds tt Eust. 60. 29. a@
, to save alive in turn, Babr. 107. 16;—in Byz. —fwypevo. dvriahtrw
GAAnAous, to warm one another, Joseph. B. J. 4. 4, 6. dévrOdmrw,
to bury opposite : Pass. aor. dvrerapny Anth. P. append. 147. dvreta,
7), (dvrieos 11) worship of false gods, Eccl: dvriBeos, 7, ov, equal to
the gods, godlike, like iaé@eos (cf. Sext. Emp. go through in
opposition, dvr. Adyq Plat. . ry 37 M. 7.6): Homeric epith. of heroes,
as distinguished for strength, beauty, > 2 avrwieképXomac —
avTixatadAayua. ete, ; also of whole nations, Il. 12.408, Od, 6. 241;
of women only in Od. 11.117 :—no moral quality is implied, as it is
applied even to Polyphemos, and the suitors, Od. 1. 70., 14.18; cf.
duvpwr. " contrary to God, impious, Nonn. Jo. 5. 166. 2. ‘as Subst.,
dv7i@eos, 6, a hostile deity, Heliod. 47> avrWepimevw, to take care
of in return, yovéas Xen. Cyr. 8. 3, 49. dvreppatve, to warm in
return, Alex. Aphr. Probl. 1. 115. avriBécrov, 76, synonym for
fav@wv (q. v.) in Diosc. 4. 138. dvrideois, ews, 7), opposition, Plat.
Soph. 257 E, 258 B; dvrideow éxetv mpds Te to be opposed to... ,
Arist. H. A. 2.11, 3 :—resistance, Anth. P, 12. 200. 2. in Logic,
opposition of propositions, Arist. Interpr, Io. 3; Top. 2. 8, Metaph. 9.
3,1, al.; cf. dvrixepac. 3. in Rhetoric, antithesis, Isocr. 233 B, Arist.
Rhet. 3. 9, 9. 4. in Gramm. the change or transposition of a letter, E.
M. 172. g., 156. 11. dvriWeréov, verb. Adj. one must oppose, 7 mpds
7 Arist. Pol. 3. 15, 10. dvrBerixés, 7), dv, setting in opposition,
contrasting, Twav Sext. Emp. P.1.8: antithetical, Eust. 1325. 19. II.
contrasted, correspondent, of metres, in which the first line of the
antistrophé corresponds with the last of the strophé, and vice versa,
Hephaestion p. 117. dvriBeros, ov, (dvririOnuc) opposed, antithetic,
dvr. cindy oddév Timocl. "Hp. ; vow éxev dvr. mpds te Plat. 2.672. B;
dperais kala dvr. Sext. Emp. M. 9. 156. 2. dvriderov, 7d, an
antithesis, At, Fr. 300 B, Arist. Rhet, Al. 27, 1. : dvriBéw, fut. -
Oevcouat, to run against another, compete in a race, Hadt. 5. 22. II.
to run contrary ways, Anth. P. 9, 822. avrOqyo, to whet against
another, ddévras éxi twa Luc. Paras. 51. dvrOAtBw, to press against,
counteract, dAAjAovs Archyt. in Stob. Ecl. p- 742 Gaisf. :—Pass.,
dvri@AiBera: 7d OAiBor pressure produces counterpressure, Arist. G.
A. 4. 3, 18. avriOvnoKw, to die in turn or for another, E, M. 114. 14.
dvrObwkKos, ov, (OBx0s) seated opposite, Greg. Naz. Arcan. 6. 44.
avrOpyvéw, to wail in return, Twi An. Ox. 3. 180. dvrBpo€w, to cry
out against, Emped. 372; Karsten dudOopdvros, avriGpovos, ‘ov,
seated opposite, Greg. Naz. Arcan. 4. 25. &vriOpoos, ov, echoing,
resounding, Coluth. 118, Anth. Plan. 1 53 dvrBupetpos [i], ov,
instead of a door, Ai@os Noun. Jo. 11. 140. dvrivpos, ov, (Bipa)
opposite the door, kat’ dvriBupov KAoins opposite the door of the
house, Od. 16.159, as the Schol.; or it may be a neut. Subst.,
dvri@upoy, the part facing the door, the vestibule, as it is in Bare
kar’ dyrtOipav Soph. El. 1433, ubi v. Herm.: in Luc. Symp. 8, the side
of a room facing the door; vads dvr. Id. Dom, 26, dvriOtw, fo
sacrifice in turn, Philox. 10, in Pass. dvrixabatpéw, to pull down or
destroy in turn, Dio C. 46. 34. avruxabev5u, fut. evdnow, to sleep
again or instead, Anth. P. 11. 366. par, Ion. dvrucar—, properly pf. of
dvrixabiCopat, but used as pres., to be set over against, Twi Archyt.
ap. Stob. 269. I1. 2. mostly of armies or fleets, to lie over against,
so as to watch each other, Hpépar oe dvrucatnpévorar eyeysveoay
dnrw Hat. 9. 39, cf. 41, Thue. 5. 6, Xen., etc.: metaph., Adyos dvr.
rut Sext. Emp, M. 1.145. dvrixabifopat, Ion, dvticat—, fut. —edodpa,
aor. —¢(éunv -—Med.: to sit or lie over against, of armies or fleets
watching one another, Hdt. 4. 3-, 5-1, Thue. I. 30., 4. 124. II. the
Act. is found in Lxx (4 Regg. 17. 26), to place or settle instead of
another. avTik pt, Ion. dvrikar—: fut. -xaracrjow:—io lay down or
establish instead, substitute, dAdAa Hat. 9. 93; ph eAdcow
dvtinaracThgat wadtv to replace an equal quantity of gold, Thuc. 2.
13; @AAovs dvr. set up others in their stead, Arist. Mirab. 94. 2. to
set against, oppose, Twa mpds Twa Thue. 4. 93; Tid Tu Plat. Rep.
591 A. 3. to set up or bring back again, dvr. emt 7d Oappeiv Thuc.
2. 65 ; rovs GopuBndevras Dion, H. 6. 11. II. Pass., with aor. 2 and
pf. act.; also aor. pass. kateordOny (Xen. An, 3. 1, 38):—to be put in
another's place, reign in his stead, Hat. 2. 37, Xen. l.c. 2. to stand
against, resist, absol., Thuc. 1. 71., 3.47, etc. ; Twi Xen. Hipparch. 7,
5. avrixatvos, ov, equal to new, Hesych. dvrikatw, Att. —Kdw, ¢o set
on fire in turn, Plat. Tim. 65 E. avrikikoupyéw, to damage in turn,
Twa Plat. Crito 49 C, 54 C. avrikixdw, =foreg., Joseph. B. J. 3. 6, 30:
—hence avrikdkwots, ews, %, injury returned, mutual damage, Eust.
Opusc. 100. 87, etc. dvriKihéw, fo invite in turn, Xen. Symp. 1, 15, in
fut. pass.—KAnOngopat. dvrikadAwmifopat, to adorn oneself in
rivalry with, Tu Plut, 2. 406-D. dvrikdparrw, to bend, direct in turn,
Byz. dvrixadvovilw, to decide or act against the canons, in Eccl, law,
Byz. avrucdpBiov, 74, in Poll. 2.165, the depression in the stomach
next its cardiac extremity: but Ruf. Ephes. (Part. Corp. H., pp. 28,
50, Clinch) makes it the depression in the throat above the clavicle,
= aparyh, Aaveavin. dvrikaptepéw, to hold out against, mpés tt Dio
C. 39. 41. avruk! , to put down or pay in turn, Liban. 4. 800.
dvtixatdyw, to bring in instead :—Pass., dvrinaraxO7jpev Tit to come
into the place of another, Tim. Locr. to D. avricatabdive, of a star, fo
set in the opposite quarter, Theo Astrol.p.178. avrikaraSviopat, to
stoop down in turn or in opposition, Ach. Tat. 6. 18. avrixatabvaoKw,
aor. 2 -€0avov:—to die or be slain in turn, de Tovs xravévras
GvrixaTbaveiv (the word dixny, which follows, being prob,
constructed with déyras or the like in a line that has been lost),
Aesch. Cho. 144 (Scalig. dvriaxraveiv, to slay in return). y a apBdvw,
to take possession of in turn, Tim. Locr, 102 D, dvricatahéyw, to
enroll instead, soldiers, senators, etc., Dio C. 54. 14.
dyrucatraketmw, to leave in one’s stead, Plat. Rep. 540 B.
aytikatahAayn, 7), exchange, Tivos mpds 7 Plut. 2. 49 D.
avrixataéhAaypa, 76, requital, Joseph. A. J. 15. 9, 2 
 dyricaTtadXakréov —ayrixopaCw. dvrixataAAakréoy, verb.
Adj. one must exchange, Arr. Epict. 4. 3. red Xhewenak, aie ’ Med.
Pas fro eae thing for avriKka: Hy :—to exc ake for another, 7 dvré
twos Lycurg. 159. 2. to receive ing in exchange for another, 7+ dvi
Twos Isocr. 138 B. 3. to wet off or balance one against another,
evepyectas xpicews Dinarch. 92. iav make some jon .. ; aver. te
wept Ta Geia compensation . . , Arist BL ALT. ‘yd > aduxobvra, ef
BAaBepdy, GAA kadéy to’strike a balance in case of injury. ., Id.
Rhet. 3. 15, 2. 4. to interchange, Id, Eth. N. 8. 5, 2, Aeschin. 66. fin.
II. Pass., dvrixatadAayival Tux to be reconciled, Polyb. 15- 20, 5- IIT.
the Act.= Med., Athanas. dyrixarapedide, fo scoff at, make a mock
of, Tivos Cyrill. Gvrixarapww, fo shut one’s eyes in turn, Poll. 9. 113.
: rw, to send down in return, Basil. , yoow, fut. fw, to frighten in
turn, App. Civ. 3. gt. Gynxatappéw, fo flow down in turn, Olympiod.
‘@, to establish instead or in turn, Dion, H. 1. 5. dyruardordons,
ews, 9, a bei gry ei at oe re poke © 47. 4: opposition, Joseph. A.
J.16. 2, 5; &¢ avrucaracrdcews C. 1, 2222.8. bo, to encamp
opposite, Dion. H. 8. 84. dynxardoxeois, ews, 1), a holding in by
force, rod mvetiparos Arist. Probl. 3. 1, 3. dynxatareive, fo stretch by
pulling against another, Hipp. Fract. 761, es Aéyopev Art. 781:
metaph., dy dytixara atte Adyov mapa if we setting speech directly in
contrast with speech against him, Plat. 348 A, cf. Plut. 2. 669 F with
aor. to overrun in turn, Dio C. 60. 9. dvrucatadppovéw, fo despise in
turn, Twds Dio C. 54. 33dvrixaraxwpiopes, ov, 6, replacement, Antyll.
Oribas. p. 98. d to accuse in turn, recriminate upon, Twos Lys. 106.
41, Aeschin. 25. 25 :—in Pass., Dio C. 36. 23. II. Pass., in Logic, to
be reciprocally predicable, to be convertible, like dvriarpépeayv,
Arist. An. Post. 1. 3, 7-, 1.13.13; dvr. rot mpayparos Id. Top. 1. 5, 4
sq., al. }, @ counter-charge, Quintil. 3. 10, 4. dvrixartfopat, Ion. for
dvrixdd-, ‘Kopat, fut.orxjoopai, Dep. toperishin turn, Walz Rhett.
1.465. Gynxartwv, wvos, d, Anticato, name of a book written by
Caesar in reply to the Cato of Cicero, Plut. Caes. 54, App. Civ. 2. 99.
r used as Pass. of dvriri@nyu, to be set over against, to correspond
with, ripa d-yaboiow dy. is held out to them as a fitting reward, Pind.
L. 7 (6). 36. II. to be opposite to, of places, rwvos Hipp. Aér. 282;
tut Strabo 120: of things, fo be opposite or opposed, my @AnAa
Plat. Soph. 258B; dvr. xara duiperpov in a circle, Arist. Cael.
1.8,11,al. 2. in the Logic of Arist., to be opposed, of propositions, .
10, Metaph. 4. 10, 1, al.; ra dyrixeipeva opposites, An. Pr. 2. 15, 24,
2, cf. 3. 10, 5. a ou Lxx (Ex, 23. 22, cf. Isai, 66. 6, al.). a ov, on the
opposite side of the way, rot xos Nonn. D.8, 191. GyruxeXetw, to
bid, command in turn, Thuc. 1. 128:—Pass. to be bidden to do a
thing in turn, Id. 1. 139. , TO, something acting as a goad, Aesch,
Eum. 136, 466. dvrixepSaivw, fo gain, receive in turn, Nicet. Bug. 3-
303dvruxndevw, to mind, tend instead of another, ur. Ion 734 :—
also Poll, 5. 142. v deputy herald, C. 1. 353. 11. 9. to proclaim in
answer to, obdiv dvrexnpuger Adryos Eur. . 673; ora eye mig pela 3:
32. andy move in opposition, Arist. Memor. 2, 29 :—Pass., dvd TO
Kwowv dytinweigOa must suffer a prcwpgeln dag Id. Phys. ‘s. §, 19,
cf. G. A. 4. 3, 18, Cael. 1. 5, 12. II. in Pass, also to make counter-
movements, move against the enemy, Polyb. 2. 66, 3. ou 4},
counter-movement, Hermes in Stob. Ecl. 1. 400. c to sound by
striking against, kpavyh .. wérpaiow dyréis echoed by them, Eur, .
1145. 2. c. acc. cogn., dvr. GAD péAos to sing against one another,
Id. Bacch. 1057. wo, Att. -xAdw, fo weep in return, Hat. 3. 14 (v. 1.
dolcnaiov), Eust. 37. iehbes to bend back, Psell. :—Pass., . Naz,
TixAs aa H, a false key, Clem. Al. $97, Poll. 10. 22:—also Med. to
have allotted to one in return, 7 Eust. Opusc. to turn or bend again,
Musae. 108. scratch in turn, dddmAovs dvr.‘ claw me, claw thee,’
ostol. Adag. 17. 20 Leutsch. —akw), fo strike on the shin, Sext. Emp.
M. 1, 217. or , 76, the part of the leg opposite the xvipn (THs
Kvhpns 7d A. I. 15, 5), the shin, Hippon. 40, Hipp. Fract. 764, hollow
of the instep, Polemo Physi 2. 27. Pass. to be punished in return,
Luc. Ty ranic. 12; e 143 dvrikoAcxevw, to flatter in turn, Plat. Alc. 24.
; dvruxopifw, tobring back as an answer, Aé-yov Plut. Lys. 26.
dvrixopmate, fut. dow, to boast in opposition, twi Plut. Anton, 62.
dvrixovréw, fo support with a pole or stick, {0A dvr. TO ohpare Hipp.
Mochl. 852; éyrt-xoréovar or ~Koraivovar ap. Erot. p. go is altered
by Foés. into -xovréovet.—But that the form in —dw is the true one
appears from the Subst. dvrixévrwots, ews. 7). the support of a stick
to a lame man, Hipp. Art. 819, 824. dvrikotnh, 7), a beating back,
resistance, Plut. 2.77 A, 649 B; in pl., Strabo 222. dvrixomrixés, 7),
dv, resisting, repellent, Sext. Emp. M. 10. 137. avrucétrrw, to beat
back, resist, oppose, 1. in a physical sense, c. ace., bray védean ..
dvricdnry mvedpa évaytioy Hipp. Aér. 285; absol., Srav mvedpa
ayrinérry vériv Arist. H. A. 8. 13, 13, cf. P. A. 1. 2, 36, Theophr. C. P.
1. 12,9; dvr. GAAHAaS, also of winds, Id. Vent. 53- 2. of persons, 6
5@ Onpapyévyns dvréxomre Aéywr .. Xen. Hell. 2. 35 15- 3. impers.,
jv te dvrixdy if there be any hindrance, Ib. 2.3.31. & bw, to make to
swell in turn, Ti O4daccav Nicet. Eug. 9. 29. a Y . Med. to take arms
against, twit Anth. P. 7. 668, Ath. 702 B. aytuc , to arrange or adorn
in turn, Plut. 2. 813 C, etc. —the Subst. $, }, in Suid. ov, 6, a deputy
koopnrns (signf. 1. 2), C. I. 272, 276, 281, 284 :—hence,
dvrxoopnteva, to discharge this office, Ib. 376. dvrixowts, ews, },
(xémra) opposition, dvéuav Theophr. Vent. 55. dvruxpafw, fut. —
cexpagopat, to shout in return, Byz. dvrixparéwo, to hold, have
instead of something else, Anth. P. 11. 298. avrixpive, fo judge in
turn, Twa Aristid. 2. 410: to compare, match, i rive Acl. :—Med. to
contend against, LXx (Job. 9. 32., 11. 3)dvrixptots, ews, ,=trd«prots,
Anaxil. Incert. 11 (v. Poll. 4. 113). ra S, ews, 7), @ striking against,
hindrance, sudden stop, Arist. Rhet. 3.9, 6, Plut. 2, 721 B: the sense
is dub. in Aeschin, 24. 10, perhaps @ repartee. dvrixpotw, fut. ow,
to strike or clash against, come into collision, 1. in a physical sense,
dAlya .. ra dvtixpovovra adrois Arist. Cael. 4. 6, 2; absol., Id. P. A. 1.
1, 45, al.; dvr. Plat. Legg. 857 B; domls dowid: Liban. 4-542. 2. in a
general sense, adrois .. rovro dvrexexpovee had been a hindrance to
them, had counteracted them, Thuc. 6. 46; dvr. Tais ovpBovAiais
Plut. Ages. 7; dvr. mpds re Id. Cato Ma. 24:—absol. to prove a
hindrance, offer resistance, dvréxpovoé te Kai yé-yover oloy obi et
Dem. 294. 20; édy dvrixpotoy Tes Arist. Rhet. 2. 2,9; dvréxpovov ai -
yovaines Pol. 2. 9, 11. avrixpv, Adv.,=dvrny, over against, right
opposite, Oeots dvtiepd ud~ xeoOa Il, 5. 130; c. gen.,”"Exropos
dvrupt Il. 8. 301. iL= Gvrikpus, straight on, right on, dvrixpd dépu
yadneov efenépnoe Od. 10. 162; dyrixpd pe Il. 13. 1374—but mostly
followed by a Prep., dyriepd 8 dv’ 5. 745 dvrucpd 3° dpov 4. 481, cf.
Od. 22, 16; wep) Kara péaoov right in the middle, Il. 16, 285; so
once in Xen., dyrixpi 80 abray Cyr. 7. 1, 30:—in a similar sense Hom.
uses waravtixpv, q. Vv. 2. outright, utterly, quite, dvrucpd 8 arépnue
Il. 7. 362; dvrixpd & € 16, 116, cf. 17. 49, Od. 10. 162, etc.: —with
> paxdpecow éixro, Ap. Rh. 4. ft we may compare bpomPhpevac
dvrny, ete—V. dvrixpus sub fin, [Hom. has 0 in arsi, & in thesi ; but
Ar. Eccl. 87 has earayri«pv, with the quantity of dyrixpus. | dvrixpis,
Adv.,=én’ ei@eias, straight on, right on, dvrixpus idv mapewadécero
tx deftGs he came straight up and .. , Plat. Euthyd. 273 B, ef. Ar. Lys.
1069, Thuc. 2. 4; also, els 7d dvr. ropeteo@at Plat. Symp. 223 B. 2.
outright, openly, without disguise, mms dvr. 145° alvécw Aesch, Cho.
192; 6 xpnopds dvr. Aéyet Ar. Eq. 128 ; edyovrai ye mAovreiv dvr. Id.
Pl. 134; dvr. py xpiiva wreiv Thuc. 6. 49; oddity H dvr. BovAclay
downright slavery, Id.1. 122; # dvr. tAevOepia 1d. 8. 64; od« avr.
not at all, ob doicovr’ dvr. ray ‘Hpaxdadav Ar. Pl. 384. 3. sometimes
of Time, straightway, evAAaBéyres d-yovew dv. ws dwoxrevowrTes
Lys. 137. 10, cf. Plat. Ax. 367 A. IE. later, =dvrixpv, opposite, Gyr.
elvat to oppose, Arist.Eth. FE. 7. 10, 20; dvr. émévat against, Dion.
H. 3. 24; waraorivat Plut. Solon 27; év 7H dvr. mvadi& C. I. (add.)
224¢, etc.; v. Lob. Phryn. 444.—The distinction between dyvrixpu,
iepus, as above given on the authority of the best authors, was
noted by the Gramm., who explained dyvixpt by é& évavrias,
dvrixpus by pavepais, duapphiny, cf. A.B. 408. Hom. used only
dyrixpv, and that in both senses; In correct Att. dyri«pus is almost
exclusively used and always in the secondary sense, xaravti«pd
being used for cyrixpv. In Trag., neither dyrixp or earayrixpt occur,
and dyrixpus only in Aescli.|.c. dvricteivw, fo slay in return, Eccl. ws,
}, acquisition of one thing for another, Plut. 2. 481 E. ov, («reiva) in
requital for murder, dvticrévors wowaic: . . warpés Aesch. Eum. 464
:—the Subst., -«rovia, 4, occurs in Eccl. dvruxrimiw, fo ring, clash
against, rw Anth. Plan. 221. dvrixrimos, ov, resounding, re-echoing,
v.1. Nonn. Jo. 20. 70. dvrixtbalve, to praise in turn, Themist, 57 D.
Pass, to boil with conflicting waves, to dash hither and thither, Plut.
2: ape Act. dyr. éaurév, in same sense, Oribas. Matth. 244:—also
dvruxuparéw, Byz. lomtheaed, 4, as equiv. for Lat. nditiakeeh,
Dacang. :—and davrixipia, 3, =éfovaia, in Suid. mute (0), aor.
dvréxupoa -—to hit upon, encounter, meet, Twi Pind. O. 12, 16,
Soph. O. C. 99, etc.; absol., Id. Ph. 545. : dynxwAtw, fo hinder by
resisting, Hipp. 412. 36:—the verb. Adj., -vréev occurs in Galen,
dvrixwpdle, to celebrate by a festival in turn, Schol. Pind.
 144 dvrixwpodiw, fo ridicule in turn, Plut. Flamin. 9.
dvrixwmnAarns, 6, =dyrnpérns, Schol. Aesch, Theb. 283. @ us, éws,
5, part of the handle of a shield, Hesych, & }, (dvr:AapBava) a thing
to hold by, a handle, Lat. ansa, dmms Gy .. pr) Exor dvriAaBhy %
xeip Thuc. 7.65; of a shield, otre ovr dvriAaBas éxe Strabo 154. 2.
metaph., oAAds . . éxee bopias cat dvr:AaBas gives many handles
against one, points of attack, Plat. Phaedo 84 C; so, vt &5évae Dion.
H. de Rhet. 8. 15; 70a Luc, Tim. 29; cf. Aa87. a fut. ers Aa pf. -
e{Anxa Dem. 1009. 4 :—as law-term, dvr. dlarrav to have a new
arbitration granted, i.e. to get the old one set aside, Dem. 542.12;
dvr. Thy ph) odoay (sc. Siarray) to get it set aside as false or
groundless, Id. 543. 14; v7. Epnuov (sc. riv dixny) to get it set aside
by default, Id. 889. 23; dvr. rds mapaypapas Id. 976. 24 :— ef. Att.
Process 756. GvrAdfopar, —vpat, post. for dvriAapBavouat, to take
hold of, hold by, c. gen., Eur. 1. A. 1227: ¢o take a share of, partake
in, mévov Id. Or. 452, etc. 2. c. acc. to receive in turn, to be repaid,
dvriAdQuTa. . road ay roxedot 5G Eur. Supp. 363. Cf. Aafopar.
GvriAakrife, fo kick against, Twi Ar. Pax 613; Tid Plut. 2. 10 C,
dvriAtkwvile, fo in L ian fashion, Eust. 1642. 51. dvmAthéw, to speak
against one, Symm. V. T. & vo, fut. —Anpouat, to receive instead of,
xpvood dwpara mAnpn Tas HBas dvr. Eur. H. F. 646 (lyr.); mostly
without a gen., ed Spav eb maduy dvriAaBeiv to receive in turn,
Theogn. 108 ; Kav... ; oexppow .., awppov’ dvriAnwerar Eur. Andr.
741; Hdoviv dévras .. kaxtav.. dvr. Thuc. 3. 58; €pavoy Arist. Pol. 7.
14, 5; dvr. dAAnv [xwpav] to seize in return, get instead, Thuc. 1.
143; dvr. dAdous twas Xen, Cyr. 5. 3, 12. II. mostly in Med., with pf.
pass. -etAnupat Lys. 180. i—like dvréxopuat, c. gen., to lay hold of,
campod meicparos avteAdBov Theogn. 1362; dxpov rod oripaxos
dvr, Plat. Lach. 184 A, cf. Prot. 317 D, al.; 7H dprorepG dvr. Tod
TpiBwvos Ib. 335 B; guAlas xwpas dvr. to gain or reach it, Thuc. 7.
77; (on Ar. Thesm. 242 v. Dind. ad 1.) :—hence in various relations,
2. to help, take part with, assist, ove dvriAjeo? ; Eur. Tro. 464; Tijs
cwrnpias, THs eAevOepias Thuc. 2. 61, 62, etc. ; of persons, dvr.
“EAAjvwr to take their part, Diod. II. 13; dvr. Tov doGevovvraw Act.
Ap, 20. 35, etc. ;—in Thuc. 7. 70, the constr. is prob. wept rijs és Tv
marpida cwrnpias—vor, ei more Kat abhis, .. dvyriAaBécOa [airfs]
now or never to give it a helping hand, 3. to lay claim to, seize on,
Tov dopadods Thuc. 3. 22; Tov Opévov Ar. Ran. 777, 787. 4. to take
part or share in a thing, take in hand, Lat. capessere, Thuc. 2.8; t@v
mpayparwv Xen. Cyr. 2. 3, 6, Dem. 15. 5, etc.; Tod modcyuov Isocr.
136 E; tis Oadarrns Polyb. 1. 39, 143 THs Appodirns Alex. Tap. 3.15;
THs madeias Plat. Rep. 534 D; dvr. rod Adyou to seize on the
conversation (to the interruption of the rest), Ib. 336 B. 5. to take
hold of for the purpose of finding fault, to reprehend, attack, hpav
Plat. Soph. 239 D, cf. Gorg. 506 A, etc.; av7tAaBw@peba let us
attack the question, Id. Theaet. 169 D; dvtiA. ds advvarov ..to object
that .., Id. Soph. 251 B, cf. Rep. 497 D. 6. to take fast hold of, i.e. to
captivate, 6 Ad-yos dvrtAapBaverai pov Id. Phaedo 88 D, cf. Parm.
130 E, Luc. Nigr. 19. 7. of plants, to take hold, take root, strike, like
Lat. comprehendere, Theophr. H. P. 4. 1, 5. 8. to grasp with the
mind, perceive, apprehend, Plat. Ax. 370 A; noted as an obsol. word
for auvinus by Luc, Soloec. 7 :—so of the senses, dvr. xaTa Thy
axony, dapphoe Sext. Emp. P. 1. 50, 64. IIL. in Med. also, to hold
against, hold back, irmov Xen. Eq. 10, 15; so, dvttAnmréov Tod
immov T@ xadw@ Ib. 8,8; cf. Arist. M. Mor. 1. 14, 2, Audib. 41.
dvriAdprw, to light up in turn, of 8 dvréAappay (sc. of pvAaxes)
Aesch, Ag. 294. II, intr. to reflect light, shine, Xen. Cyn. 5, 18; mpos
Thy cednvny Plut. Arat. 21. 2. to shine opposite to orin the face of, 6
Hdwos dvr. rivi Plat, Mar, 26, etc.: to dazzle, rwi Id. 2. 41C, 420 F.
dvrikapifis, ews, 7), reflexion of light, Plut. 2.930 D, 931 B. dvnAéyw,
Hdt., Com., and Att. Prose (cf. dvrayopedw):—fut. dvridégw Eur.
Hipp. 993, Ar. Ran. 998, Xen.; but the common fut. is dvrepo :— aor.
dvréAefa Soph. O. T. 409, Ar. Nub, 1040 (but the aor. commonly
used is dyretrov): so the pf. is dvretpnea, the fut. pass. avrepyvopat.
To speak against, gainsay, contradict, Twi Thuc. 5. 30, Plat., Xen.,
etc, ; wept twos Thuc. 8.53; tet mepi twos Xen. Mem. 4. 4, 8; bnép
twos Ib. 3.5, 12; mpds te Ar. Nub. 888 :—often foll. by a dependent
clause, dvr. ds .. 0 declare in opposition or answer that .., Hdt. 8. 77,
Ar. Eq. 980, Thuc. 8. 24, Xen., etc.; od Todrd 7 avTiAéyouow, ws ov
.. Arist. Pol. 3.16, 11; also, dvr. bmép Twos ds .., Thuc, 8. 45; soc.
inf., dvr. mojoev tadra, jv ..to reply that they will.., if.., Id. 1. 28; dvr.
ph woeiy to speak against doing, Id. 3. 41, Xen. An. 2. 3, 25; dvr. ph
ob dgcodc0ai twa Xen. Cyr. 2. 2, 20. 2. c. acc, rei, to’ dvridégat (v.
supr.) Soph. O. T. 409: av. tii 7 to allege something against .., Thuc,
5. 30; dvr. Adéyov Lys. 113. 19; pd0ov ayz. Tivi to tell one tale in
reply to another, Ar. Lys. 806; so Med., dvriAéyeaOai 7 mpds Twa
wept Tivos Dem. 818. 13 :—Pass. to be disputed, questioned,
avTik@pmdew — avTimerro. dvridntts, ews, %, a motion for a new
arbitration, Dem. 1006. 14; ¥. sub dyTiAayxave. dvrAnmréov, verb.
Adj. one must take part in a matter, Ar. Pax 485 ; Tov mpayparav
airois dvr. Dem. 9. 13, cf. 13. 15. IE. y. dyriAapBarw 11. avrAntriés,
7, dv, able to apprehend, ASéyov Tim. Locr. 100 C; divas dvr. wAnyis
dépos Plut. 2. 98 B: assisting a creeper to cling, ytoxpérns Theophr.
C, P. 1. 6, 4: sustaining, supporting, twds Eust. Opusc. 160. 14 :—
Ady. —«@s, Justin. M. 2. pass. to be perceived by the senses, revi
Cass. Probl. 35. II. able to check, Def. Plat. 416, dvriknips, ews, ,
(dvriAapBdvw) a receiving in turn or exchange, Thuc. 1, 120: a
counter-claim, Xen. Hell. 3. 5, 5. II. (from Med.) a laying hold of in
turn, reciprocation, Democr. ap. Arist. Fr. 202 ; of plants, a taking
root, Theophr. C, P. 3. 6, 6: the clinging of a vine by its tendrils, Ib.
2, 18, 2. 2.=dvriAaBn, a hold, support, Xen. Eq. 5, 7; of a bandage,
Hipp. Offic. 743 ; dvrianyw Bondeias txew Diod. I. 30; dvr. d:ddvac
Twi to give one a handle, Plut, 2. 966 E. 3. defence, help, succour, t
Ep, Cor. 12. 28. 4. a claim to a thing, Xen. Hell. 3. 5, 5 5. an
attacking, objection, Plat. Phaedo 87 A, Soph. 241 B, Hipp. Ma. 287
A :—a demurrer, Rhet. 6. grasping with the mind, apprehension,
Tim. Locr. 100 B, Diod. 3. 15 ; motor: Plut. 2. 625 B. III. (from
Pass.) a being seized, seizure, attack, as by sickness, Thuc, 2. 49. ;
avriAtriivedw, to entreat in return, Plut. 2. 1117 C. dvrtA6Buov, 74, a
part of the ear, opp. to mpoddBuov, Poll. 2. 86. dvridoyéw, fut. now,
=dvriAéyw, to deny, Soph, Ant. 377. dyriAéyw 3, Ar. Nub. 322 :—in
Med., Antipho ap. Poll. 2. 120. avtioyla, 4, contradiction, controversy,
disputation, Lat. di: eptatio, dvr. xpnopa@v contradiction of the
oracles, Hdt. 8. 77; #péas.. és dvr. mapé£opev will offer ourselves to
argue the point, Id, 9. 87 ; é3éxeov ayriAoyins Kupnoev expected to
be allowed ¢o argue it, Ib. 88; Lys. Fr. 45.1, Plat., etc.; és dvr. rwi
Thuc. 1.73; dvr. cal Aotdopia Dem. 1018. 8; dvriAoyiay €xe it
involves contradiction, Arist. Rhet. 3. 17, 16, cf. 13, 3; in pl.
opposing arg ts, ing speeches, Ar. Ran. 775, Thuc. 4. 59 :—dvr. mpés
twa Xen, Hell. 6. 3, 20; és dvr. €AOeiv Thuc, I. 31; avriAoyiay év
atT@ éxew to have grounds for defence in itself, Id. 2. 87.
dvrioyilopat, Dep. to count up or calculate on the other hand,
Antipho 117. 13; dvr. 671.., Xen. Hell. 6.5, 24. dvridoyucés, 77, dv,
given to contradiction, contradictory, disputatious, Ar, Nub. 1173,
Isocr. 319 B, Plat. Theaet. 197 A, al. :—1) —K«7 (sc. Téxv7), the art
of contradiction or of arguing JSrom contradictories, Id. Rep. 453 E,
Phaedr. 261 D; so, 7d —xév Id. Soph. 225 B:—of —Koi persons
skilled in this art, Id. Lys. 216 A; and of the arguments, of mepi Tous
Adyous dvriAoyiKods darpivavres Id. Phaedo go B, cf. 101 E. Adv. —
K@s, in the of such disputants, Id. Theaet. 164 C. dvrioytopes, 6, a
countercharge, Philostr. 549. dvridoyos, ov, contradictory, reverse,
r¥xat Eur. Hel. 1142. dvrAoBopéw, to rail at or abuse in turn, Plut. 2.
88 E, 1 Petr. 2. 22: —Med., c. acc. rei, Luc. Conv. 40. dyridotos, ov,
slanting, oblique, Byz. dvrthitéw, fo vex in return, Plut. Demetr, 22,
Luc. D. Meretr. 3. 3. avrAvmpos, ews, 7, avexing in return, Arist. de
An. 1.1, 16, Plut. 2.442 B. dvridvpos, ov, (AUpa) responsive to the
lyre, Soph. Tr. 643. dvrikutpov, ov, 7d, a ransom, I Ep. Tim. 2. 6, 2.
in Orph, L. 587, an antidote, remedy. dvriAutpéw, to ransom in
return :—verb. Adj. dvriAvtpwréov, Arist. Eth, N. 9. 2, 4.
dvriAwBdopat, Dep. to maltreat in return, Eust. 757. 59.
dvripatvopat, Pass. to rage or bluster against one, Luc. D. Meretr, 12.
2; Twi Anth. Plan. 30. dvripavOdve, to learn in turn or instead, Ar.
Vesp. 1453dvripavris, ews, 6, a rival-prophet, Schol. Lyc.
dvtipaptipéw, to appear as witness against, Ar. Fr. 382: to contradict
solemnly, tii or mpds Tt Plut. Alc. 21., 2. 471 C; revds Ib. 418 A.
dvripaptipyots, 7), counter-evidence, Sext. Emp. P. 2. 244; in pl.,
Plut. 2, 1121 E. dvripapripopat [0], Dep. to protest on the other
hand, Luc. Symp. 47. dvripaxéw, to resist by force of arms, Diod.
Excerpt. 502. 69. 2. as law-term, fo resist, demur, A. B. 184.
dvripdxnors [4], ews, 9, a conflict, struggle, én’ ddAnAas Dion. H. 8.
58 :—dvripaxyrus, %, Eratosth. ap. Schol. Ven. Il. 19. 233.
dvripaxntys, od, 6, an antagonist, Or. Sib. 14. 165. dvripaxopar, fut.
—yaxnoopa:, Dep. to fight against one, Thue. 4. 68. dvripaxos, ov,
fighting against, rwi App. Hisp. 9; cf. Ath. 154 F. dvripeyadoppovew,
to vie in pride or boasting with, ii Eust. 676. 5. dvripePeAxw, to drag
different ways, distract, Anth, Plan, 136, 139, in Pass.; 7 xat 7H
Anth. P. ro. 74. . it aac fut. —ueraorjaw :—to move from one side to
the other, tor ise, Ynplopara cat vépoy Ar. Thesm. 362. II. Pass.,
Tests, Xen. Hell. 6.5, 37; of a place, émd rivos dvtiAeyopevov ter-
claimed, Tb. 3. 2, 30. 3. absol. to speak one against the other, speak
in opposition, Hdt. 9. 42, Eur., Ar,, etc.; 6 dvriAéywv the opponent,
Plat. Prot. 335 A; of dvriA€éyorres Thuc. 8. 53. dvriAexréov, verb.
Adj. one must gainsay, Eur. Heracl. 975. dvritexros, ov, questionable,
to be disputed, dpos odx dvr. Thuc. 4. 92. dvriketis, ews, 7, an
answer, Hipp. 24. 44. 2. dialogue, avriAdgeas rev broxpirav, opp. to
povwdiat, Philostr. 244. dvreoxatvw, to chatter against, Perictyoné
ap. Stob. 458. 3. dvrihéwy, 6, lion-like, formed like dyri#eos, Ar. Eq.
1044; where however it is, in fact, a proper name. with aor. 2 and pf.
act. to pass one into the other, to be interchangeable, dvr, GAAnAos
76 Te Vdwp Kai 6 anp Arist. Phys, 4. 2, 5, cf. 4. 4, 13, Meteor. 2. 8,
27; cf. dvrimeptiornus I. 2: to pass to the other side, Luc. | Dem.
Enc. 37. ‘ dvripetpixrevouar, Dep. to behave petulanily in return,
mpds Twa Plut. Sull. 6. : dvripeAeraw, to study or practise in
emulation, Athanas. dvripeAtlw, to compete in music with, twit Anth.
P. 5. 222. av7péAAw, to wait and watch against one, dvtipehAjoat
Thuc. 3. 12, $ as restored by Bekk. for the MS. reading
dvrempeAAjoar.
 SSS dvriéeupouat —dyrirranos, dvripéephopar, Dep. to
blame in turn, retort upon one, dvr. brt.., pa Se a eee rt ep. in * v .
P. 6. 209. dvripecroupivéw, fo be in the opposite meridian, as the
sun at midnight, Plut. 2. 284E. ~ é av 76, the opposite meridian,
Sext. Emp. M. 5. 12. dvriperaBaive, fo pass over in turn, évi tt Alex.
Trall. 6. 2, p. TOI. L . to meet one change with another, Hipp. Acut.
388. q, 7, transposition, as a figure of speech, Longin. 23, cf. 85.
ews, }, a mutual exchange, Eust. Opusc. 50. 63. dvrmerdects, ews,
#, @ counterchange, Longin. 26, GvriperaxAive [7], fo turn aside or
the opposite way, Philo 1. 678. ww, fo assume in turn or in
exchange, 7 Plut. 2. 785 C:—Pass. to be transformed, A.B. }, a pear
aape: the opposite, Plut. 2. 438 D; dvr. rev Bio experience of divers
kinds of life, Ib. 466 B. GyriperadAevw, to countermine, Polyb. 1. 42,
12., 16. 31, 8. dvripetapptw, to flow off in turn or back, Plut. 2. 904
A. , fut. -cxagw, to draw off in a different direction, eis Tt J A, J. 13-
5, 3- 7 i €ws, }), counter-c ‘e, reciprocal replacement, Arist. Phys. 4.
I, 2: of circumstances, Dion. H. 3. 19. , €wS, 2), interchange of
position, as in using one word for another, Dion, H. de Thuc. gt.
dvriperatacow, fut. fw, to change the order of battle so as to meet
the enemy, Dion. H. 3.25. x. . to go away to the other side,
dvriperax. Tais éAriat to make room for new hope, Joseph. A. J. 15.
2, 2. XOpYCIS, ews, 7), interchange, of letters, etc., Eust. 1618. 36.
to compete with others: of dyriperiévres rival competitors, Plut.
Comp. Aristid. c. Cat. 2. : to measure out in turn, to give one thing
as compensation for another, 7é rut Luc. Amor. 19: Pass.,
dvriperpnOhoerat bpiv it shall be measured in turn, Ev. Matth. 7. 2,
Luc. 6. 38 :—hence, —nors, «ws, #, recompense, Byz, yo a ale front
to front face toface, Xen. Hell. 4. 3, 19, Ages. 2, 12. : i 7 , TO,
synon, of 0 (q. v.), Diosc. 4. 76. ‘ , to rage, be wrathful against, Suid.
v Pass. to be informed in reply, Nicet. Eug. 2. 315. Dep. to contrive
against or in opposition, dAAa dvr. Hat. oBeorhpia kwdkvpara Thuc.
7.53: absol., Eur. Bacch. 291, Arist. H. A. 9. 8, 5; pds 7: Xen. Hell. 5.
3, 16. dvrpnxavnpa, aros, 7d, an engine or device used against
another, pac dyriu. ebrpenifew Polyaen. 4. 2, 20. , «ws, %, close
imitation of a person in a thing, c. dupl. gen., 7-07. ov, closely
imitating, rwés Alcidam. ap, Arist. Rhet. 3. 3, 3; ¢. dat., dp@adrpdy
dvr. HAiov rpox@ Ar. Thesm. 17. dvruptotw, to hate in return, Ar.
Lys. 818. %, @ requital, recompense, Ep. Rom. 1. 27,2 Cor. 6. 13.
ov, as a reward, in compensation, pyhuny dvtipobov niper’ éy Alrass
Aesch. Supp. 270. dvryucOwrés, dv, hired as a substitute, Hesych. to
rival in love, Diod. - 550.97. And, dvrpYnoThp, jpos, 6, a rival suitor,
rwds Schol, Clem. Al. 31. one Ady. by way of compensation, Dem.
946. 28, as restored by olf, dvripoipéw, fo receive a proportionate
share, Poll. 4. 176. %, ae aR as in some Mss, of Dem. l.c, sub
dvriporpel. ov, =ladporpos, q. v. dvripodetv, (v. Adoxa) to go to
meet, Apoll. Lex. Hom.s, v.dvr:BoAjoat. dvripoAmos, or, ing instead
of, dvr. dAoAvyHs Kanvrés a shriek of far other note than the cry of
joy, Eur. Med. 1176; tmvov 768’ dvripodmoy .. Gos song, sleep’s
substitute, Aesch. Ag. 1 i ov, ate sep to, rwi C. I. 160. 26 (p. 273).
ov, after, corresponding toa thing, Luc. Amor. Ady. —pws, ru Plut.
Crass. 32. - bi ov, sounding responsive, @bais dvr. wéAos Niceph. in
Walz Rhett. 1. 493. ae ieheas, Dep. 40 bellow in answer, rwvi Dion.
H, 1. 39. Peres. to mock in turn, ap. Cic. Fam. 25. 19, 4. vi @ tax on
sailors, Byz. dvrwavpiixéw, to fight against one at sea, Byz.
dyrwavmnytw, to build ships against, Thuc. 7. 36, 62, in Pass. Dep,
to swim against, mpds xia Plut. 2. 979 B. to conquer in turn, Aesch.
Cho, 499, cf. Dio C. 48. 21, ps aad an ambiguity in the law, Plut.
2.742 A; bv dytito be im a strait between two laws, Id, Caes. 13.
Pass. joe ip ropes pene Tvos, prob., laws enacted against one, yt.
ap. Stob. 267. 39. Gvrwopixés, 7, dv, relating to ambiguity in the
laws, Plut. 2. 741 D. Ady. «ds, Schol. Dem. 592. ; , to make laws
against, rivi Plut. 2. 1044 C, etc. dyrivoos, ov, opposite in character,
resisting, tt Hipp. 1184 F. dvrwouleriw, fut. how, fo warn in return,
Plut. 2. 72 E. Gyrivwros, ov, in pl., back to back, Diod. 2. 54. ; , 40
entertain a gévos in return, Eust. 1961. 37. to set against, oppose
to, Pind. O. 13. 47. ov, contr, 145 pevor obdév age pavfcerbat
avritooy Hdt. 7. 218, cf.6. 50; 7d... rota. Exvonar avr. 4-129; otparov
.. dvr. Mépanar 6. 7 cevabeale éy pupinae weno piny obit Exw
dvrigooy 8. 119; dvr. dodpa Ap. Rh. 2. 79; 7d dyrigoov opposition,
Hdt. 1.174; 70 dvr. ovppépov Heraclit. ap. Arist, Eth. N. 8. 1,6. Adv.
dvrigéms in hostile spirit, Philostr. 315. (The Root seems to be {¢w,
though it is not easy to see the connexion of sense.) dvrigtw [0], fo
scrape in turn, dvr. tov gvovra, ‘claw me, claw thee? Sophron ap.
Suid. (Mus. Crit. 2. 355). avriov, as Adv. =dyrny, v. sub ayrios.
dvriov, 76, a part of the loom, Ar. Thesm. 822 ; called by Poll. 10,
125, icrov dytior. 2. generally the loom, dvriov ipaive LXxx (2 Regg.
21. 19, al.). dvrbopat, fut. copa Hdt. 7. 9, 102, al.: aor. pass.
AvTuhOnv, Ion. dvr-, Id. 4. 126., 7. 9, al.: Dep. To resist, oppose, Twi
Id. 1. 76, Aesch. Cho. 389, etc.; revi és waxnv Hat. Il. c.:—absol., of
dyriovHevor =o évayTiot, Id. 1. 207., 4. I. 2. in Hdt. 9. 7, ¢. acc., rov
Tépony dvrimoeo@at és Ti Bowriay that ye would meet him in
Boeotia. Rare in Att. (v. supr.), é€vavridopar being the form in
general use,— The Homeric forms dyridw, dvtidwot, etc., belong to
dyTiaw. dvrios, ia, lov, (dvi) set against, and so I. in local sense, face
to face, opposite, dvriot éoray dmayres Il. 1. 535; dvrios RAGE Oéwy
went running ¢o meet him, 6. 54; 4 8 ob« dOphaa divar’ dyin
though she faced him, Od. 19. 478; esp. in battle, Il. 11. 216, etc.;
éxmpeor .. of Tlépoa dvrioe Hdt. 9. 62; é« rod dvriov Xen. Cyr. 1. 4,
8 :—often c. gen., which often precedes, ’Ayapépvovos dyrios éAOwy
Il. 11. 231, cf. 5. 301., 7. 98; but also follows, dvr. #Av@’ dvaxros
Od. 16. 14, cf. Il, 17. 31, etc.: less often in Hom, c. dat., ds pa of
dvr. HAE 15. 584, cf. 7. 20; but mostly so after Hom., dvria: rots
Mépona: iCovro Hat. 5. 18, cf. Pind. N. 10. 149, Eur. Supp. 667, Xen.
An. 1. 8, 17, etc.; also, dvrios mpés rt Od. 17. 33.4. 2. in Att.,
opposite, contrary, rov dvtiov Toiade Aéyov Aesch. Ag. 499 ;
Tobrors'dvria opinions opposed to these, Eur. Supp. 466; ddcia pev
dvzia 8 otcw with pleasure [I speak], though I shall offer contrary
counsel, Soph. Tr. 122; of dvriow =oi évavri, Pind. P. 1. 86, Hdt. g.
62; dvr. yiyvec@a: =tvayrwiaba, Id. 8. 140: é« THs dyrins
contrariwise, Ib. 6; eis rd dvriov Xen. Eq. 12, 12 :—Xen. has the rare
construct., Ad-yor dyrios H obs Hxovoy words the very reverse of
those I have heard, An. 6. 6, 64. II. as Adv. in neut. dvria and dytior,
like dvrny and dvra, against, straight at, right against, absol., dvriov
Ifev Od. 14. 79, etc. ;—more oft. like a Prep. c. gen., dv7i’ éueio
orhaea0a Il. 21. 481; dvria deoroivns pdaba: before her, Od. 15.
377; so, dvria cev in thy presence, Hdt. 7. 209, cf. 1. 133; dvttov Tod
peydpov Sacing it, Id. 5.77; Tas kaphAous érage dvtia THs trou Id.
1. 80, cf. 3. 160, al.; rdvdpds dvriov wodeiy Soph. Tr. 785 : so, 2.
against, ds Tis acer dvriov (-ia?) ety Il. 1. 230; dvriov abray paviy
iévac Hdt, 2. 2; dyria twos épifay Pind. P. 4.508; c. dat., lévat dvria
trois Mépagat és paxny Hdt. 7. 236; dvriov ru Pind, N. 1. 36. 3. in
the phrase rov 8 dyriov oda Od. 15. 48, dvr. nbda—=tpelBero,
answered. The word is almost confined to Poets and Ion. Prose; in
Att. Prose évayrios is p Xen. uses dyrios. The Ady. dyrioy for évaytioy
is hardly to be found in Att. III. dyria, 74, the tonsils, v. dvTioropia.
dvrio-crdriw, =dv0icrapyai, to be contrary, of a wind, Soph. Ph. 640.
dvrio-ropia, %, excision of the tonsils, Ermerins Anecd, Med. 155.
dyrioxevopat, Pass, fo drive against, Anth, P. 11. 284. dvriéw,
dvriéwoa, etc., v. sub dytidw. year age gp to contend in the
maryxparioy, Schol, Philostr. 818. %, a suffering instead, Aumet Tov
arepspevoy Tav dyabav } dvr. xaxdy Plat. Ax. 370 A, cf. Aeschin. Dial.
3. 16, II. a Seelin to another, antipathy, Plut. 2. 952 D, al. vai Bagg
have an aversion, Alex, Aphr. dvrumibys, és, (waos) in return for
suffering, Aesch. Eum, 782: felt mutually, jbovh Luc. Amor. 27. 2. of
opposite feelings or properties, Sivas Plut. 2. 664 C; ptow éxev dvr.
mpds 7 Ib. 940 A :—Adv. as, Geop. 5. 11, 4. II. as Subst., dvruradés,
76, a remedy for suffering, Plat. Anton. 45, Hesych. : also,
dvruma@tov, 76, Hesych. :—the name was given to a black kind of
coral, Diosc. 5. 140. GvrumatSevw, fo teach as a rival master, Tiwi
Suid. Gvrumailw, to play one with another, Xen. Cyn. §, 4, Plat. Eryx.
395 B. dvrimats, 4, 3, like a boy or child, ypais Aesch. Eum, 38;
6vyarpds dytimaiBos Eur. Andr. 326. II. instead of a boy, i.e. no
longer a boy, Soph. Fr. 148: so in late Prose, as Polyb. 15. 33, 12.,
27-13,4. Cf. dviOeos. dvrimatw, fo strike against, resist, 70
dvrvmaioy Hipp. Vet. Med. 18, ef. Arist. Probl. 11, 29, 1; mpés 7+
Polyb. 18. 29, 15. dvruravovifw, to sing the battle song against,
dAAHAos Max. Tyr. 32. 6. a device for resistance, Greg. Nyss.
dvruridaoris, ob, 6, an antagonist in wrestling, Ael. V.H. 4. 15.
dvrumaidale, to wrestle against, Schol. Ar. Ach. 570, Eccl.
=dyrinxavdopat, Eccl. :—the Subst., —-qors, 7), Byz.
dvriumdéhAopat, Pass. to rebound, Cass. Probl. 26, Eust. 948. 12.
dvrimidos, ov, (méAn) properly wrestling against: hence struggling
against, antagonist, rival, ps te dyr. hee Pr. 529; dvr. Tui rivalling
another, Eur, Bacch. 544; c. gen., uévos yhpaos dyrimador Pind. O.
8. 94:—as Subst., dvrimados, 6, an antagonist, rival, adversary, Pind.
N. 11. 33, Soph. Ant. 125 ; mostly in pl., Hdt. 7. 236, Ar. Ran. 365,
1027, al. ; 10 dytimadov the rival party, Thuc. 2. 45, etc. ; 6 8 Ader
és ravrimadoy Eur. Bacch. 278. 2. of things, like lodmados, nearly
matched, nearly balanced, ¢ dvrimddov mapackevijs Thuc. 1. 91;
avr. Tpnpns equally large, Id. 4. 120; dvr. rut Id. 1. 11; -yw@pac dvr,
mpds GAANAas Id. 3. 49; dvr. Béos fear caused by the balance of
the power, of the parties, mutual fear, Id. 3. 11; dvr. wowat
adequate punishment, Eur. ovy :—Ion. word, opposed to, adverse,
dand- BL T. 446; 90ca dvrinada [rp éAc] habits te tt 7 J to.,, Thue.
 146 2. 61; dvr. ri a match for him, Id. ¥. 11; ipevaiew ydos
dvrimados Eur. Alc. 922:—10 dyrimadoy rijs vavpaxias the equal
balance, undecided state of the action, Thuc. 7. 71, cf. 34,38;
dvrimada karacrica to bring ¢o a state of balance, Id. 4. 117; eis dvr.
karaorivat to be in such state, Id. 7. 13 :—Adv. —Aws, Id. 8. 87; also
neut. pl., vavpayncaves dyrimaka Id. 7. 34. ITI. in a pecul. sense,
rdv dydy avr. him who fights for me, my champion, Aesch. Theb.
417. ayrura evopat, Dep. to deal craftily with or against, Twi Eccl.
avre 2, fut. -BUA®, to hold side by side, so as to compare or
contrast, 7. mpés Tt or mapa 7 Plat. Apol. 41 B, Hipp. Mi. 369 C,
Isocr. rir B; ri re Arist. Fr. 82; Blov twos kai rivos Plut. Ti. Gracch. 1:
— Pass., c. dat., App. Civ. 2.15. II. to contribute instead, Xen. Lac. 5,
3. avrurapaBAnréov, verb. Adj. one must compare, An. Ox. 3. 216
(where -rév). dvrurapaBoAn, 7, close comparison or contrast, Arist.
Rhet. 3. 13, 3-5 19, 5TaknenpugeAlé: %, competition for a public
office, Plut. Arat. 35. dvrurapayyéAAw, fut. Ad, to give orders,
command in turn or also, Xen. Hell. 4. 2, 19. II. to compete for a
public office, Plut. Mar. 29, Caes. 7; Tiwi with one, Id. Cato Mi. 49.
Cf. maparyyéAAw. avrimapaypidy, 7), a counter-napaypapy, a
replication, Gloss. ayturapaypadw, Zo add or insert on the other
side, Ptol. :—Med., as law-term, to reply to a mapaypapn, Gloss.
avrimapdyw, to adduce, allege on the other side, Plut. 2. 719 C: but
mostly, II. intr. to lead the army against, advance to meet the
enemy, Xen. Cyr. 1. 6, 43. 2. to march parallel with, rwi Polyb. 1. 77,
2, etc. dvrirapiiywyh, 7, an advancing against, Polyb. 9. 3, 10, al. II.
in pl. Aostility, mpés twa Id. 10. 37, 2, al. dyrumapadeixvupr, to
compare, contrast, rid ri Greg. Nyss. dvrimapabldwyt, to deliver upin
turn, rhy apxny rit Joseph. A. J. 15.3, 1. dvrumapadects, ews, 1),
comparison, contrast, Joseph. c. Ap. 2. 33, Eccl. avrimapaberos, ov,
put or to be put in comparison with, Epiphan. dvrimapabéw, to
outflank, Xen. An. 4.8, 17. II. to run parallel zo a thing, Plotin. 6. 5,
11. avrurapalewpéw, to examine by contrasting, Greg. Nyss.
avturapaivéw, Zo advise contrariwise, c. inf., Dio C. 65. 11.
dyrurapakaAtw, fut. éow, fo summon in turn or contrariwise, émt
édnGeorépay ye cwrnpiay Thuc.6. 86, cf. Xen. Cyr. 2.2, 24, Plat.
Gorg.526 E. dvru eypat, Pass, to lie just opposite, rive Polyb. 3. 37,
7- 2. in Gramm., to correspond with, ri Apollon. de Ady. 625. ave
eAevopat, Dep. to exhort in turn or contrariwise, Tois mpeoBurépos
pa) KaracxuvO7jva Thuc. 6. 13, cf. Xen. Cyr. 3. 3, 42 and 59.
dvrurapdkAnots, «ws, %, exhortation on both sides, Polyb. 11. 12,
2. avrumapadapBdve, to compare by contrasting, Galen.
dvturapadtméw, to annoy in turn, Thuc. 4. 80. dvrimapaméptropat,
Pass., dvr. 77 wvnun to be cheered on one’s way to death by the
remembrance, Plut. 2. ogg D. avrurapamiyvupr, to fix near or
opposite, Apollon. de Constr. 37. avrurapamAéw, to sail along on the
other side, Thuc. 2. 83. dvrimapatropevopat, Pass., =dvrimdperye,
Polyb. 5.7, 1. avrv evdfopat, Med. to prepare oneself in turn, arm on
both sides, Thue. 1. 80, etc.; dvr. GAAHAOS ds és paxny Id. 7. 3. II.
later, in Act. to prepare against, set on, T1va Tin Dio C. 38. 14.
avrumapackeun, 7, hostile preparation, Thuc. 1. 141.
avrimapdoraois, ews, %, as a figure of speech, a counter-objection,
a replication, objection, Apsin. 55 Bike :—Adj. -oramixés, 4, dv, Byz.;
Adv. —«@s, Eust. 704. 36. avrv irotreSevw, to encamp opposite,
Dion. H. 8. 25. avruraparagis, ews, 7), hostile array, dvrimapardgets
xara Tiv Gyopav Dion.H.6.22; dvr. rijs yvm@pns stubborn
determination to resist, Joseph. A. J. 18. ba avrimapataccopat, Att. -
rropar, Med. and Pass. to stand in array against, Tt Thuc. 6. 98;
dvrerapareraypévous mpos Tiv TovTwy acédyevay Aeschin. 90. 16:—
absol. to stand in hostile array, Thuc. 1. 63, Xen.; awd rod
dvrimaparayGévros in hostile array, Thuc. 5.9; in a Com. metaph., 4
Snuovpyds dvrimapareraypévn xpegdt’ drr@ Menand. Wevd. 1.12.
II. the Act. is used =Med. in Polyb. 9. 26, 4. dvrimapatetva, to
stretch side by side so as to compare or contrast, Gddov AGyov
mpos abrov dvr. Plat. Phaedr. 257 C dvrirapartOnpt, fo contrast and
compare, tf Gddas vieras tary avr. Plat. Apol. 40D, cf. Menand.
Mrooy. 1; of the Hexapla, Eus. H.E.6.16, 4. dvrumapatpémw, to turn
in the contrary way, Cyrill. dvriumapaxwptw, to give way in turn,
Basil.:—Subst. -xapyors, 7, mutual concession, Eust. 445. 11.
dvrimdpetpe (fu: ibo), to march so as to meet, of armies on opposite
sides of a river or entrenchments, Xen. An. 4. 3, 17, Hell. 5. 4, 38.
dvriumapexSviopat, Pass. to slip out, emerge in turn, Synes. 17 B.
dvrimapéxriicts, ews, 1), equal extension, Chrysipp. in Stob. Ecl. 1.
376, Philo 1. 433. avrumapexreivopat, Pass. to spread out beside,
Chrysipp. in Stob. Ecl.1.376. & yw, to lead on against the enemy, Tiv
Sivayv, Tov troy Plut. Lucull. 27, Pyrrh. 16. 2. (sub. orpardv) to
march against, like dvrimapdyw, Philipp. ap. Dem. 239. 6: metaph.
to contend in controversy, Tivi with one, Sext. Emp. M. 7.166. b. to
march parallel with, rivi Plut, Aemil. 30. II. to compare, éavrdy mpds
twa Id. 2.470 B. avrimapekiywyn, %, a means of attack in
controversy, mpés Twa Sext. Emp. M. 7. 150. dvrvmapebeupn, = dy
rimdperur, Plat. 2.195 C. dvrimapetépyopat, Dep. =foreg. Dio C. 47.
46. & avTiravoupyevouat — avrimepisTaw. dvrumapeteratw, to
confront with, Dion. H. 3. 11:—Subst. é tacts, 7, Eust. Opusc. 255.
40. 2 ess dvrurapépxopat, Dep. to pass by on the opposite side, Ev.
Luc. ro. 31: c. ace. loci, Anth. P. 12. 8. II. to come up and help, as
against an enemy, Lxx (Sap. 16. 10). avrurapéxe, to furnish or
supply in turn, Thuc. 6. 21; also in Med., Xen. Hier. 7,12,
Anth.P.9.12. —-&.. to cause in return, rovs dvtimapéfovras mpaypara
Dem. 555. 12. dvrurapnyopéw, fo persuade, comfort in turn, Plut.
2.118 A. dyre » to stretch along parallel to, rots eipnyévots, c. dat.,
Arist. Mund. 3, 10, cf. Strab. 128 :—to outflank, 7} orpatevpart Paus,
8. 10, 6. dvritapSevetw, to lead a virgin life in turn, Eumath. P.
333dvrurapurmevw, to bring their cavalry against, Arr. An. 5. 16.
dyturaptorapat, Pass. to correspond, Ptol. dvrimapodevw, to meet on
a march, GAAHAos App. Pun. 107. dvrumappyordfopat, Dep. to
speak freely in turn, Plut. 2. 72 E. dvrimap@déw, to write a parody
against, rit Strabo 394. avrv éopat, Pass. to be opposite in name or
expression, Nicom. Arithm. 77; the Act. in same sense, Iambl. :—
Subst., -rapwvupia, 7, Tambl. ; and Adj., -tapavupos, ov, Nicom.
Arithm. 110. dvrumdoxe, fut.—eicopar: aor.—€miOov :—to suffer in
turn, xaxé (or ka~ k@is) dvr. to suffer evil for evil, Antipho 126.16;
7i dv dp4ceay abrous, 6 7 ode dy peiCov dvrimdborev; Thuc. 6.35;
Spay avrimdoxw xpnora I receive good for good done, Soph. Ph.
584; dv7’ eb meicera: Plat. Gorg. 520 E (v. sub dvrevmdoxw) ;
xaddv 70 eb mroreiv wa) iva dvrimdOy Arist. Eth. N. 8.13, 8;—also,
dvr. dvri rivos Thuc. 3.61: absol. to suffer for one’s acts, Xen. An,
2.5,17. 2. 70 dvrimenovO6s, reciprocity, Arist. Eth. N.5. shan sq.; but
of persons, ebvoray év dytimerovO6o1 gidiay eivat good-will in cases
of reciprocity, Ib. 8. 2, 3. 3. to stand in the same relation, mpés 7 Id.
Mechan. 3, 2. II. to counteract, rivi Diosc, 3. 70, 74. pes 4 to be of
opposite nature to, twi Theophr. Lap. 14, Polyb. 34° 9. 5 IV.
dvrimerovO6ra reflexive verbs, Diog. L. 7. 64. dvrumirayéw, to rattle
so as to drown another sound, yépw Thuc. 3. 22. dvruelOw, to
persuade or try to persuade to the contrary, Jo. Chrys. dvrureotixés,
7, dv, availing to persuade to the contrary, Bachm. An. 2, 291.
Riressoahdgphin to cherish in turn, and évruredGpynors, or (in
Schol. Soph.) -ywors, ews, 7, and —yta, 7, love in return, esp. the
mutual love of parents and children, Aristaen, 1. 25, Glycas Ann, p.
41 B, Suid., etc.; v. Jacobs Ael. N. A. 20 p. 114. Cf. oropyn.
avruréutrn, to send back an answer, Hdt.2.114,Soph.O.T. 306:—
Pass., Hat. 6.4, 2. to send back sound, echo, Arr. An. 6.3, 3- 3. to
sendin requital or repayment, oixovpia Soph. Tr. 542; Tet Onpiov
Philem. Neaép. Xr. II. to send against, orparidv ri Thuc. 6. 99. Tit. to
send in the place of another, orparnyovs émt rds vais Id. 8. 54.
dvrimepus, 7), a sending back of sound, an echo, Arr. An. 6. 3, 3.
avrurevOys, és, causing grief in turn, Aesch. Eum. 782.
dvtimetrov0és, v. sub dv7imacx@ :—Adv. —OéTws, Archimed.
Aequilibr. 1.7; and Subst., —memévOnots, 7, Nicom. Arithm. p. 75.
avrumépa, Ady. for dvrimépay, Polyb. 1.17, 4, etc. desimapaknis.
pierce in turn, sensu obscoeno, Anth. P. 12. 238. avrurepardopar,
Pass. to be carried, pass over again, Sozom. dytumépatos, a, ov,
lying over against, dvtimépar évépovto the lands lying over against,
Il. 2. 635 :—in late Ep. also a fem. dvrimépard, Ap. Rh. 2. 351, Dion.
P. 962; so, in Tzetz., dvrv TUS, 7. avturépav, Ion. —nv, Adv.,
=dyvrinépas, Xen, Hell. 6. 2, 9. II. Adj., "Agida 7’ dvrimépny re Asia
and the opposite coast, Mosch. 2. 9. avrumépas, Adv. over against,
on the other side, c. gen., Thuc, 2. 66, etc.; absol., 9 dvr. @pden Id.
1. 100, cf. 4. 92. dvrumepaw, =dvrimepardopar, Byz. dvrumépyev,
Adv. from the opposite side, Ap. Rh. 1. 613; c. gen., Id. 2. 1031,
Anth. P. 9. 551. dvrureptdyw, to bring round against, Tov 6&
[oxoprioy] 7d Kévrpov énatpovra dvtimepiaye Arist. Mirab. 139; so of
the corvus employed on the Roman ships, Polyb. 1. 22, 8.
dvrumepttiywyn, %, opposite motion, Ptol. avrureptBddAw, to put
Welcome to our website – the ideal destination for book lovers and
knowledge seekers. With a mission to inspire endlessly, we offer a
vast collection of books, ranging from classic literary works to
specialized publications, self-development books, and children's
literature. Each book is a new journey of discovery, expanding
knowledge and enriching the soul of the reade

Our website is not just a platform for buying books, but a bridge
connecting readers to the timeless values of culture and wisdom. With
an elegant, user-friendly interface and an intelligent search system,
we are committed to providing a quick and convenient shopping
experience. Additionally, our special promotions and home delivery
services ensure that you save time and fully enjoy the joy of reading.

Let us accompany you on the journey of exploring knowledge and

personal growth!

textbookfull.com