MIDTERM L2: Radiosensitivity and 4.

The greater the proliferation and growth

Response rate for tissues the radiosensitivity.
-This law concludes that compared to a child or
The Law of Radiosensitivity: Jean Alba mature adult, the fetus is most radiosensitive
Bergonie and Louis Tribondeau
-In 1906, two French scientists, Bergonie and The Law of Ancel and Vitemburger
Tribondeau, theorized and observed that In 1925, embryologists Paul Ancel and P.
radiosensitivity was a function of the metabolic Vitemberger modified the law of Bergonie and
state of tissue being irradiated. Basically, the Tribondeau. They suggested that the intrinsic
law states that the radiosensitivity of tissue susceptibility of damage to any cell by
varies within maturation and metabolism. ionizing radiation is identical, but that the
✓The law has found some application in timing of manifestation of radiation-produced
radiation oncology. damage varies according to the cell type.
✓In diagnostic imaging, the law serves to Their experiments on mammals demonstrated
remind us that the fetus is considerably more that there are two factors that affect the
sensitive to radiation exposure than the child manifestation of radiation damage to the cell:
or mature adult. 1. The amount of biologic stress the cell
The Law of Radiosensitivity receives.

-Genital area of the mature male rabbit; 2. Pre- and post-irradiation conditions to
penis, testes and adjacent anal glands which the cell is exposed.
-In 1906, radiologist Jean Alba Bergonie and
physician Louis Tribondeau observed the The Law of Ancel and Vitemberger
effects of radiation by exposing rodent ✓They determined that a given dose of
testicles to X-rays. radiation will cause the same degree of
The Law of Bergonie and Tribondeau damage to all cells but only if and when the
✓The testes were selected because they cell divides will damage be demonstrated
contain both mature and immature cells ✓Even though Ancel and Vitemberger convey
✓The mature cells execute the organ’s radiosensitivity differently than Bergonie and
principle functional cells. Tribondeau, they do agree with them by
✓The spermatogonia cells divide frequent, placing a significant emphasis on the
amount of mitotic activity involved.
whereas the spermatozoa cells do not divide.
✓After irradiating the testes, Bergonie &
UNDIFFERENTIATED CELL
Tribondeau noticed the immature cells were
injured at lower doses than the mature cells.
 ✓ one that has few specialized morphologic
or functional characteristics.

✓Supported by their observations, they

radiation sensitivity for all body cells which is ✓ an immature cell whose primary function is
the and Tribondeau. to divide, thus providing cells a way to maintain
Their law maintains that actively mitotic and its population and to replace mature cells lost
undifferentiated cells are most susceptible to from the end population.
damage from ionizing radiation. ✓ It is considered precursor or stem cell in a
The law states that: population.
1. Stem or immature cells are more
radiosensitive than mature cells. DIFFERENTIATED CELL
2. Younger tissues and organs are more ✓ one which is specialized functionally
radiosensitive than older tissues and organs. and/or morphologically.
3. The higher the metabolic cell activity, the ✓ considered a mature cell or end cell in a
more radiosensitive it is. population.
DIFFERENTIATION - allows for less effect because the body can
-refers to the sum processes whereby have time for repair of cellular organisms as
undifferentiated cells become specialized well as recovery of tissues affected.
functionally and/or morphologically • Even though the same dose is delivered to
(structurally). two different individuals, if it is delivered more
quickly to one of them, it will cause more harm
Radiosensitivity of tissues
Highly radiosensitive 3. FRACTIONATION
-Lymphoid tissue - The division of large doses of radiation
-Bone marrow needed for treatment into smaller radiation
-Gastrointestinal epithelium doses (usually daily increments). 

-Gonads - Fractionated dose is one that is delivered at
-Embryonic tissues the same dose rate but divided into equal
Moderately radiosensitive
fractional quantities of radiation. 

-Skin
- Reduces effect because cells undergo
-Vascular endothelium
-Lung repair and recovery between doses 

-Kidney - Used in radiation therapy since it allows
-Liver time for tissue repair and recovery between the
-Lens (eye) radiation treatments. 

Least radiosensitive -The concept of fractionation for radiation
-Central nervous system (CNS) therapy came from French experiments in the
-Muscle 1920s and 1930s. Ram testes were exposed
-Bone and Cartilage to x-rays. It was found that the animals could
-Connective tissue not be sterilized with one large dose without
also causing skin reactions at the scrotum.
Lethal Dose 50/30 However, if the dose were fractionated (split
into smaller amounts) over time, the animals
✓Dose which would cause death to 50% of
could be sterilized without causing much skin
the population in 30 days.
damage. It was postulated that the testes were
✓Its value is about 2-3 Gy for humans for a model of a growing tumor, whereas the
whole body irradiation.
 skin of the scrotum represented a dose-
limiting normal tissue.
Cell Survival and Recovery
The factors influencing cell survival and 4. PHASE OF THE CELL CYCLE
recovery: - Generally, the most radiosensitive phase of
1. LINEAR ENERGY TRANSFER (LET) the cell cycle is M . G2 is also considered to
- Low LET radiation generally causes be radiosensitive. The most resistant phase
sublethal damage to DNA, repair enzymes is late S. G1 is also considered to be
can usually reverse the cellular damage. radioresistant.
- High LET radiation causes multi-strand - cells that have a high replication rate are
breaks in DNA, repair enzymes are not more sensitive to radiation damage.

effective at undoing this damage, and hence
cell death will probably occur.

2. PROTRACTION
- A protracted dose is one that is delivered
continuously but at a lower dose rate. 

- When radiation is administered over a long
period of time but at a lower rate, the effect of a
large dose is lessened.
5. PRESENCE OF RADIATION MODIFIERS
A. Radiosensitizers
- agents that enhance the effect of radiation.
- these drugs make the individual about twice
as sensitive to radiation than normal
B. Radioprotectors
- agents that reduce the effects of radiation
upon cells.
- A group of chemicals called sulfhydrils have
a radioprotective effect, but are too toxic for
human use.

FIVE “R’s” OF RADIOBIOLOGY

1. REPAIR
- the process of rejoining DNA strands.
- Most repairs occur within 15 minutes to 1
hour

2. REOXYGENATION
- occurs as the sensitive, well-oxygenated
tumor cells are killed and the tumor shrinks

3. REPOPULATION
- the ability of the cell population to continue
to divide and to replace dying and dead cells

4. REDISTRIBUTION
- reflects the variability of a cell’s
radiosensitivity over the cell cycle 

- Cells in different parts of the reproductive
cycle have different sensitivities
- M is the most sensitive, and late S is the
least sensitive

- Radiation exposure kills more of the cells in
the M phase, and more cells in the S
phase survive

5. RADIOSENSITIVITY
-The relative susceptibility of cells, tissues,
organs, organisms, or other substances to the
injurious action of radiation

JANEY RT 22 :>
LECTURE 1 (MIDTERM) Radiation Effects II. Single-strand Break
(Part 1) - The ionization of a DNA macromolecule
SUBCELLULAR RADIATION EFFECTS resulting in a break of one of its chemical
A. Radiation Effects on DNA bonds, thereby severing one of the sugar-
phosphate chain side rails or strands of the
ladderlike DNA molecular structure
- This type of injury to DNA is called a point
mutation

III. Double-Strand Break

I. Change or loss of a base (Mutation)

- destroys the triplet code and may not be
reversible
- the direct consequence of this damage is an
alteration of the base sequence
- may cause acute consequences for the cell
but more important if the cell III. Double-Strand Break
remains viable, incorrect genetic information -It is the ionization of a DNA macromolecule
will be transferred to one of the two daughter that results in the rupture of one or more of
cells when the cell divides. its chemical bonds, thereby creating one or
more breaks in each of the two sugar-
phosphate chains of the DNA ladderlike
molecular structure
- It is not fixed as easily as single-strand
breaks
- It is also called frameshift mutations

IV. Double-Strand Break in the same Rung

of DNA

II. Single Strand Break

Radiation Effects on DNA

-It is the result is a cleaved or broken
A single-strand break (SSB) can be repaired easily, chromosome , with each new portion
because the opposite strand serves as a template. containing an unequal amount of genetic
material
-If this damaged chromosome divides, each
new daughter cell will receive an incorrect
amount of genetic material.
-This will culminate in either death or Radiation Effects on ChromosomesSingle
impaired functioning of the new daughter cell Break Effect
1. One arm of one chromosome
V. Covalent Cross-Links A. Restitution
- rejoining and healing of the broken ends of
the chromosome
- No damage to cell

V. Covalent Cross-Links
- It is the chemical unions created between
atoms by the single sharing of one or more
pairs of electrons
-It is directly initiated by high-energy radiation.
-At low energies, however, are probably
caused by the process of indirect action
2. One arm of two chromosome
Covalent Cross-links patterns: A. Acentric chromosome
1.Intrastrand cross-link -It is a cross-link that - joining of 2 chromatids without a centromere
form between two places on the same DNA B. Dicentric chromosome
strand
- joining of two chromatids with centromeres.
2. Interstrand cross-links - It happen
C. Translocation
between complementary DNA strands or
between entirely different DNA molecules - joining of acentric fragment from one
chromosome to the fragment containing the
3. DNA molecules also may become covalently
centromere of the other chromosome
linked to a protein molecule
- Normal appearing chromosome but there is a
change in its gene
3 Principal observable effects that may
result from irradiation of DNA
Radiation Effects on Chromosomes: Double
1. Cell death Break Effect
2. Malignant disease -Chromosome appears normal, contain original
3. Genetic damage number of genes and DNA, however the
sequence of bases has been altered.
SUBCELLULAR RADIATION EFFECTS
B. Radiation Effects on Chromosomes 1. One arm of one chromosome
A. Deletion
Chromosome Structure

B. Inversion
A. Deletion -A few hundred centigray (cGy) can kill very
- process wherein the fragments between the sensitive cells such as lymphocytes or
break is deleted. spermatogonia
- Deleted fragments is lost during cell division -For less radiosensitive cells, such as those
- The acentric fragment will join with the in bone, apoptosis may require radiation
fragment with centromere form a normal doses of several thousand cGy
looking chromosome but lacking in genetic
material B. Mitotic (Genetic ) Death
B. Inversion - occurs when a cell dies after one or more
- the fragment with broken ends turn around divisions
and rejoin thereby reversing its position - even relatively small doses of radiation can
on the chromosome. cause this type of cell death
- the radiation dose required to produce mitotic
death is less than the dose needed to produce
Radiation Effects on Chromosomes: Double apoptosis in slowly dividing cells or nondividing
Break Effect cells
2. Both arms of one chromosome
C. Mitotic Delay
-the failure of the cell to start dividing on time
-exposing a cell to as little as 0.01 Gy of
ionizing radiation just before it begins dividing
can cause mitotic delay
-after this delay the cell may resume its normal
mitotic function
-the underlying cause of this phenomenon is
2. Both arms of one chromosome not known
A. Acentric chromosome
B. Inversion D. Reproductive Failure
C. Ring chromosome -generally results from exposure of cells to
- results when broken ends of the fragment doses of ionizing radiation in the range of 1 to
with the centromere moves about and twist 10 Gy
before joining -the cell does not die , it permanently loses its
ability to procreate but continues to metabolize
CELLULAR RADIATION EFFECTS: TYPES and also to synthesize nucleic acids and
OF CELL DEATH proteins
A. Interphase Death -the termination of the cell's reproductive
abilities does, however, prevent the
- apoptosis, or programmed cell death
transmission of damage to future generations
- cell death before entering mitosis of cells.
- A nonmitotic, or non-division, form of cell
death that occurs when cells die without
E. Interference with function
attempting division during the interphase
portion of the cell life cycle. -Permanent or temporary interference with
cellular function independent of the cell's ability
- occurs spontaneously in both normal tissue
to divide can be brought about by exposure to
and in tumors.
ionizing radiation
-the more radiosensitive the cell is, the
-If repair enzymes are able to fix the damage,
smaller the dose required to ca use
the cell can recover and continue to function
apoptotic death during interphase
INDIVIDUAL RADIATION EFFECTS
1. SOMATIC EFFECTS
The effects develop in an exposed
individual.
a. Short Term
b. Long Term

C.Stochastic (probabilistic) effects

- It is also referred to as the statistical
response
- Increasing the dose increases the
probability of damage, but the severity of the
effect is independent of the dose
- Cancer induction and genetic effects are
stochastic effects governed by probability

3. DETERMINISTIC EFFECTS
-formerly called non-stochastic effect
-thought to be threshold, as there are doses
below which the effect is not observed
-Examples are radiation burns, cataracts,
erythema, fibrosis, and hematopoietic
damage
-The increase in severity with dose, and thus
are considered to be threshold.

4. GENETIC EFFECTS
The effects of radiation on the embryo and
fetus depend on the stage of development
and the radiation dose.
MIDTERM L3: Systemic Response to Relative Radiosensitivity of Tissues and
Radiation Organs Based on Clinical Radiation
Oncology
RADIO TISSUES OR EFFECTS
Radiation causes the ionization of: SENSITIVITY ORGAN
High: 200 to 1000 Lymphoid Tissue Atrophy
ATOMS -which will affect rad (2 to 10 Gy)
MOLECULES -which may affect Bone marrow Hypoplasia
CELLS -which may affect Gonads Atrophy
Intermediate: Skin Erythema
TISSUES -which may affect organs which 1000 to 5000 rad
may affect WHOLE BODY. (10 to 50 Gy)

Gastrointestinal Ulcer
tract
The principal organ systems of the body Cornea Cataract
are the: Growing bone Growth arrest
1. Nervous system Kidney Nephrosclerosis
Liver Ascites
2.Reproductive system Thyroid Atrophy
3. Digestive System LOW: 1000 to Muscle Fibrosis
5000 rad (10-50
4. Respiratory System Gy)
5. Endocrine System Brain Necrosis
Spinal Transection


HUMAN BODY
✓The cells of a tissue system are identified
by their rate of proliferation and their stage HUMAN BODY
of development. Atrophy: loss of muscle tissue
✓As a cell matures through growth and Hypoplasia: underdevelopment or
proliferation, it can pass through various incomplete development of a tissue or organ.
stages of differentiation into a fully Erythema: skin reddening due to injured or
functional and mature cells.
 inflamed capillaries
✓Stem cells are more sensitive to radiation Ulcer: A sore on the lining of your stomach,
small intestine, and esophagus.
than into a mature cell.
Cataract: partial opacity or cloudiness in the
crystalline lens and results from damaged
Response to Radiation is Related to Cell
cells covering the posterior
Type
surface of the lens.
RADIOSENSITIVITY CELL TYPE
Nephrosclerosis: Hardening of the walls of
HIGH Lymphocytes the small arteries and arterioles of the kidney.
Spermatoginia Ascites: It is the build-up of fluid in the belly,
Erythroblasts often due to severe liver disease.
Intestinal crypt cells Fibrosis: damaged fibers within the muscle

INTERMEDIATE Endothelial cells Necrosis: Typically results in endothelial cell
Osteoblasts damage and small- vessel injury, resulting in
Spermatids
decreased tissue perfusion.
Transection: Tear within the spinal cord
Fibrolasts
LOW Muscle cells JANEY RT 22 :>
Nerve cells