RADIATION BIOLOGY

Radiation biology is the study of the action of ionizing radiation on living organisms • The action is
very complex, involving physics, chemistry, and biology. The physics aspect of it is that; this involves
different types of ionizing radiation, the chemistry aspect involves Energy absorption at the atomic
and molecular level leading to its biology aspect of; biological damage, and Repair of damage in
living organisms. When radiation encounters living cells, it can cause heating effect, break chemical
bonds, or ionize molecules. The most serious biological damage results when it fragments or ionizes
molecules. The damage ionization of molecules does to biomolecules in living organisms can cause
serious malfunctions in normal cell processes, thereby taxing the organism’s repair mechanisms and
possibly causing illness or even death.

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Radiation can harm biological systems by damaging the DNA of cells.

TYPES OF RADIATION

Radiation can be broadly classified into two (2):

1) Non-Ionizing radiation
2) Ionizing radiation.

Non-ionizing radiation

This is a type of low-energy radiation that does not have enough energy to remove an electron or
negative particle from an atom or molecule. They are lower-frequency electromagnetic radiation
and they include; visible light, infrared, microwaves, radio waves, and lower-frequency of ultraviolet
rays.

Energy absorbed from non-ionizing radiation speeds up the movement of atoms and molecules and
thereby causing a heating effect and requiring a large amount of it before a dangerous level can be
reached. This type of radiation cannot cause cancer.

Ionizing radiation

These are higher energy radiations that act by breaking bonds or removing electrons in biological
molecules, thereby disrupting their structure and function.
Types of ionizing radiation

 Electromagnetic radiations – X-rays and Gamma-rays

 Particulate radiations –
 Electrons, protons, a-particles, heavy charged particles
 Neutrons
 Directly ionizing radiation: All charged particles
 Indirectly ionizing radiation: X and Y-rays, as well as neutrons.

If radiation is absorbed in a biologic system, ionizations and excitations occur in a pattern that
depends on the type of radiation involved. Depending on how far the primary ionization events are
separated in space, radiation is characterized as sparsely ionizing (x-rays) or densely ionizing
(aparticles).

All living things are made up of protoplasm that consists of inorganic and organic compounds
dissolved or suspended in water. The smallest unit of protoplasm capable of independent existence
is the cell. • Cells contain inorganic compounds (water and minerals) as well as organic compounds
(proteins, carbohydrates, nucleic acids, lipids). •

The two main constituents of a cell are the cytoplasm, which supports all metabolic functions within
the cell, and the nucleus, which contains the genetic information (DNA). •

Human cells are either somatic cells or germ cells. • Cells propagate through division; division of
somatic cells is called mitosis, division of germ cells meiosis. •

When a somatic cell divides, two cells are produced, each carrying a chromosome complement
identical to that of the original cell. The new cells themselves may undergo further division and the
process continues.

Somatic cells are classified as; Stem cells: exist to self-perpetuate and produce cells for a
differentiated cell population (e.g., stem cells of the hematopoietic system, epidermis, mucosal
lining of the intestine).

– Transit cells: cells in movement to another population (e.g., a reticulocyte which is differentiating
to become an erythrocyte).

- Mature cells: cells that are fully differentiated and do not exhibit mitotic activity (e.g., muscle cells,
nervous tissue).

A group of cells that together perform one or more functions is referred to as tissue. A group of
tissues that together perform one or more functions is called an organ. A group of organs that
perform one or more functions is a system of organs or an organism.

CLASSIFICATION OF RADIATIONS IN RADIOBIOLOGY

For use in radiobiology and radiation protection the physical quantity that is useful for defining the
quality of an ionizing radiation beam is the linear energy transfer (LET).
In contrast to the stopping power that focuses attention on the energy loss by an energetic charged
particle moving through a medium, the LET focuses attention on the linear rate of energy absorption
by the absorbing medium as the charged particle traverses the medium.

The International Commission on Radiological Units and Measurements (ICRU) defines the LET as
follows:

"LET of charged particles in a medium is the quotient dE/dl, where dE is the average energy locally
imparted to the medium by a charged particle of specified energy in traversing a distance of dl".

In contrast to the stopping power with a typical unit of MeV/cm, the unit usually used for the LET is
keV /µ m. The energy average is obtained by dividing the particle track into equal energy increments
and averaging the length of track over which these energy increments are deposited.

Typical LET values for commonly used radiations are:

- 250 kVp x ray : 2 keV /µ m

- cobalt-60 gamma ray : 0.3 keV/µ m

- 3 MeV x ray : 0.3 keV/µ m

- 1 MeV electron : 0.25 keV/µ m

Values for other less commonly used radiations are:

- 14 MeV neutrons : 12 keV/µ m

- heavy charged particles : 100-200 keV/µ m

- 1 keV electron : 12.3 keV/µ m

- 10 keV electron : 2.3 keV/µ m 398

X rays and gamma rays are considered low LET (sparsely ionizing) radiations, while energetic
neutrons, protons and heavy charged particles are high LET (densely ionizing) radiations. The
demarcation value between low and high LET is at about 10 keV/µm.

CELL CYCLE AND CELL DEATH

The cell proliferation cycle is defined by two well-defined time periods:

(1) mitosis M where division takes place, and

(2) the period of DNA synthesis S.

The S and M portions of the cell cycle are separated by two periods (gaps) G1 and G2 when DNA is
not yet synthesized but other metabolic processes take place.

• The time between successive divisions (mitoses) is called cell cycle time. For mammalian cells
growing in culture the S phase is usually in the range of 6-8 hours, M less than an hour, G2 in the
range of 2-4 hours, and G1 from 1-8 hours, making the total cell cycle in the order of 10-20 hours. In
contrast, the cell cycle for stem cells in certain tissues is up to about 10 days.

• In general, cells are most radiosensitive in the M and G2 phases, and most resistant in the late S
phase.
• The cell cycle time of malignant cells is shorter than that of some normal tissue cells, but during
regeneration after injury normal cells can proliferate faster.

• Cell death for non-proliferating (static) cells is defined as the loss of a specific function, while for
stem cells it is defined as the loss of reproductive integrity (reproductive death). A surviving cell that
maintains its reproductive integrity and proliferates indefinitely is said to be clonogenic.

IRRADIATION OF CELLS

When cells are exposed to ionizing radiation the standard physical effects between radiation and
atoms or molecules of the cells occur first and the possible biological damage to cell functions
follows later. The biological effects of radiation result mainly from damage to the DNA which is the
most critical target within the cell; however, there are also other sites in the cell which, when
damaged, may lead to cell death. When directly ionizing radiation is absorbed in biological material,
the damage to the cell may occur in one of two ways: direct or indirect action.

Direct action in cell damage by radiation

In direct action the radiation interacts directly with the critical target in the cell. The atoms of the
target itself may be ionized or excited through Coulomb interactions leading to the chain of physical
and chemical events that eventually produce the biological damage. Direct action is the dominant
process in interaction of high LET particles with biological materials.

Indirect action of cell damage by radiation

In indirect action the radiation interacts with other molecules and atoms (mainly water, since 80% of
a cell is composed of water) within the cell to produce free radicals that can, through diffusion in the
cell, damage the critical target within the cell. In interactions of radiation with water short-lived yet
extremely reactive free radicals such as H2O+ (water ion) and OH

• (hydroxyl radical) are produced. The free radicals in turn can cause damage to the target within the
cell.

• The free radicals that break the chemical bonds and produce chemical changes that lead to
biological damage are highly reactive molecules because they have an unpaired valence electron.

• About two thirds of the biological damage by low LET radiations (sparsely ionizing radiations), such
as x-rays or electrons, is due to indirect action.

• The indirect action can be modified by chemical sensitisers or radiation protectors.

• For the indirect action of x-rays the steps involved in producing biological damage are as follows:
Step 1: Primary photon interaction (photoelectric effect, Compton effect, pair production) produces
a high energy electron.

Step 2: The high-energy electron in moving through tissue produces free radicals in water.

Step 3: The free radicals may produce changes in DNA from breakage of chemical bonds.

Step 4: The changes in chemical bonds result in biological effects.

Step (1) is in the realm of physics; step (2) in chemistry; steps (3) and (4) in radiobiology.

Fate of irradiated cells

Irradiation of a cell will result in one of the following four possible outcomes:
(1) No effect

(2) Division delay: the cell is delayed from going through division.

(3) Apoptosis: the cell dies before it can divide or afterwards by fragmentation into smaller bodies
which are taken up by neighbouring cells.

(4) Reproductive failure: the cell dies when attempting the first or subsequent mitosis.

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