Radiobiology, IOR nowe, Radiobiologia
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Chapter 14
BASIC RADIOBIOLOGY
N. SUNTHARALINGAM
Department of Radiation Oncology,
Thomas Jefferson University Hospital,
Philadelphia, Pennsylvania,
United States of America
E.B. PODGORSAK
Department of Medical Physics,
McGill University Health Centre,
Montreal, Quebec, Canada
J.H. HENDRY
Division of Human Health,
International Atomic Energy Agency,
Vienna
14.1. INTRODUCTION
Radiobiology, a branch of science concerned with the action of ionizing
radiation on biological tissues and living organisms, is a combination of two
disciplines: radiation physics and biology. All living things are made up of
protoplasm, which 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 and 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, while division of germ cells is called 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.
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Somatic cells are classified as:
●
Stem cells, which exist to self-perpetuate and produce cells for a differen-
tiated cell population (e.g. stem cells of the haematopoietic system,
epidermis and mucosal lining of the intestine);
●
Transit cells, which are cells in movement to another population (e.g. a
reticulocyte that is differentiating to become an erythrocyte);
●
Mature cells, which are fully differentiated and do not exhibit mitotic
activity (e.g. muscle cells and 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.
14.2. 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, which 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 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, which has 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 rays: 2 keV/
µ
m.
Cobalt-60
g
rays: 0.3 keV/
µ
m.
●
3 MeV X rays: 0.3 keV/
µ
m.
●
1 MeV electrons: 0.25 keV/
µ
m.
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●
BASIC RADIOBIOLOGY
LET 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 electrons: 12.3 keV/
µ
m.
— 10 keV electrons: 2.3 keV/
µ
m.
X rays and
g
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/
µ
m.
14.3.
CELL CYCLE AND CELL DEATH
The cell proliferation cycle is defined by two well defined time periods:
●
Mitosis (M), where division takes place;
●
The period of DNA synthesis (S).
The S and M portions of the cell cycle are separated by two periods (gaps)
G
1
and G
2
when, respectively, DNA has not yet been synthesized or has been
synthesized but other metabolic processes are taking place.
The time between successive divisions (mitoses) is called the cell cycle
time. For mammalian cells growing in culture the S phase is usually in the range
of 6–8 h, the M phase less than an hour, G
2
is in the range of 2–4 h and G
1
is 1–
8 h, making the total cell cycle of the order of 10–20 h. 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 G
2
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 of non-proliferating (static) cells is defined as the loss of a
specific function, while for stem cells and other cells capable of many divisions
it is defined as the loss of reproductive integrity (reproductive death). A
surviving cell that maintains its reproductive integrity and proliferates almost
indefinitely is said to be clonogenic.
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CHAPTER 14
14.4. IRRADIATION OF CELLS
When cells are exposed to ionizing radiation the standard physical effects
between radiation and the 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 that, 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.
14.4.1. 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 the interaction of high LET particles with biological material.
14.4.2. Indirect action in cell damage by radiation
In indirect action the radiation interacts with other molecules and atoms
(mainly water, since about 80% of a cell is composed of water) within the cell
to produce free radicals, which 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 H
2
O
+
(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.
Indirect action can be modified by chemical sensitizers or radiation
protectors.
The steps involved in producing biological damage by the indirect action
of X rays are as follows:
●
Step 1: Primary photon interaction (photoelectric effect, Compton effect
and pair production) produces a high energy electron.
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BASIC RADIOBIOLOGY
●
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) is in chemistry; steps (3) and
(4) are in radiobiology.
14.4.3. Fate of irradiated cells
Irradiation of a cell will result in one of the following nine possible
outcomes:
●
No effect.
●
Division delay: The cell is delayed from going through division.
●
Apoptosis: The cell dies before it can divide or afterwards by fragmen-
tation into smaller bodies, which are taken up by neighbouring cells.
●
Reproductive failure: The cell dies when attempting the first or
subsequent mitosis.
●
Genomic instability: There is a delayed form of reproductive failure as a
result of induced genomic instability.
●
Mutation: The cell survives but contains a mutation.
●
Transformation: The cell survives but the mutation leads to a transformed
phenotype and possibly carcinogenesis.
●
Bystander effects: An irradiated cell can send signals to neighbouring
unirradiated cells and induce genetic damage in them.
●
Adaptive responses: The irradiated cell is stimulated to react and become
more resistant to subsequent irradiation.
14.5. TYPE OF RADIATION DAMAGE
14.5.1. Timescale
The timescale involved between the breakage of chemical bonds and the
biological effect may be hours to years, depending on the type of damage.
If cell kill is the result, it may happen in hours to days, when the damaged
cell attempts to divide (early effects of radiation). This can result in early tissue
reactions (deterministic effects) if many cells are killed.
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