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Spermatogenesis
Interphase
CHAPTER 6 Overview of Cell Biology
MEIOSIS
secondary
spermatocyte
107
spermatogonium
Prophase
primary
spermatocyte
Oogenesis
Interphase
oogonium
Metaphase
Metaphase
primary oocyte
Late anaphase
Early telophase
Late anaphase
Early telophase
Second
meiotic
division
secondary
spermatocyte
secondary
oocyte
Second
meiotic
division
spermatid
spermatid
spermatid
spermatid
ootid zygote
spermatozoa
spermatozoa
spermatozoa
spermatozoa
(fertilized ovum)
Sequence of steps in
oogenesis is identical to
that in spermatogenesis
through telophase
Fig. 6.19 Diagram of meiosis. Four cells result from one germ cell. In spermatogenesis, four spermatids
become mature spermatozoa. In oogenesis, one ootid may be fertilized, and three second polar bodies
remain nonfunctional.
indicates that sperm and egg cells begin meiosis with
twice the amount of genetic material as the original parent cell. Thus, at the beginning of meiosis, the number
of chromosomes increases from 2n to 4n (n 5 23).
The various phases of meiosis are similar to those
of mitosis. The main difference between the two types
of cell division begins at the end of telophase. In meiosis, after the parent germ cell has formed two daughter
cells, each of which (in human beings) contains
first polar body
(nonfunctional)
second polar bodies
(nonfunctional)
46 chromosomes, the daughter cells divide without
DNA replication. Chromosome duplication does not
occur at this phase of division. These two successive
divisions result in the formation of four granddaughter cells, each of which contains 23 chromosomes. This
ensures that the proper number of 46 chromosomes
will be produced when a female ovum containing 23
chromosomes is fertilized by a male sperm containing
23 chromosomes.
108
CHAPTER 6 Overview of Cell Biology
BOX 6.8 Female Reproductive Cell Terms
Oogonium: One of the undifferentiated germ cells that
can give rise to oocytes
Ovum: A female reproductive cell (i.e., egg cell) ulti-
mately capable of developing into an individual after
fertilization
Oocytes: An immature egg cell that matures during the
menstrual cycle
Ootid: An egg cell that results from the second mitotic
division of an oocyte
During meiosis, the sister chromatids exchange certain chromosomal material (genes). This process, called
crossover, results in changes in genetic composition and
traits that can be passed on to future generations.
Multiple Births. Multiple births can occur during a
pregnancy in one of two instances. The first method is
if an ovum, or egg cell, splits after fertilization and two
separate offspring develop. The two offspring would be
referred to as monozygotic (coming from one zygote)
twins. Monozygotic twins are also known as identical
twins because they contain exact replicas of genetic
material. Another method to achieve a multiple birth is
if more than one ootid (see Box 6.8) is available for
fertilization and the separate ootids are fertilized by
separate spermatozoa. In this case the children have no
more resemblance to each other than other children
born at different times from the same parents. Such
dizygotic twins are also known as fraternal twins. More
than two such twins would be known as polyzygotic
siblings. Fraternal twins or multiple siblings, as with
siblings born in different pregnancies, sometimes bear a
striking resemblance to one another. However, unless
they were monozygotic, they are not identical twins and
do not have exact copies of all their chromosomes.
Interphase = 2n
Prophase = 4n
Telophase = 2 (2n)
2n
1n 1n 1n 1n
Spermatozoa
Post second
meiotic division = 4(n)
Fig. 6.20 This figure indicates the total amount of genetic
material at different stages of meiosis of a male germ cell.
Twenty-three chromosomes, half the amount needed to produce a new human organism, are needed in the spermatozoa.
If 23 chromosomes are referred to as an amount of genetic
material n, then before meiosis (during interphase) the germ
cell has 2n. During prophase, this number doubles to 4n. There
then follows two reduction divisions to form the final 1n
(23 chromosomes) in the spermatozoa. An egg cell, or ovum,
undergoes a similar process, but only one of the four resulting
germ cells at the end of the process is functional.
Male germ cell
2n
nn n n
SUMMARY
• The cell is the fundamental component of structure,
development, growth, and life processes in the
human body.
• Cells are made of protoplasm, which consists of pro-
teins, carbohydrates, lipids, nucleic acids, water, and
mineral salts (electrolytes).
• Proteins are essential for growth, the construction
of new body tissue, and repair of injured or
debilitated tissue; they may function as hormones
and antibodies.
• The primary purpose of carbohydrates is to provide
fuel for cell metabolism.
CHAPTER 6 Overview of Cell Biology
109
• Lipids act as a reservoir for long-term storage of
energy, insulate and guard the body against the
environment, and protect organs.
• Nucleic acids (DNA, RNA) carry genetic information necessary for cell replication.
• RNA has the nitrogenous base uracil as a component
of its ladder steps, whereas DNA has thymine instead
in its ladder steps.
• Genes are segments of DNA that are the basic units
of heredity.
• The Human Genome Project has mapped the entire
sequence of DNA base pairs on all 46 chromosomes.
This project has led to the discovery of more than
1800 disease genes.
• There are 2.9 billion base pairs arranged into
approximately 30,000 genes.
• Water, the primary inorganic substance contained in
the human body, comprises approximately 80% to
85% of the body’s weight, is essential to sustaining
life, and serves as the transport vehicle for materials
the cell uses or eliminates.
• Mineral salts keep the correct proportion of water in
the cell, support proper cell function, assist in the
creation of energy, aid in the conduction of impulses
along nerves, and prevent muscle cramping.
• Cells have multiple components or subunits called
organelles.
• The cell membrane surrounds the human cell, functions as a barricade, and controls passage of water
and other materials into and out of the cell.
• Cytoplasm is the portion of a cell outside the nucleus
in which all metabolic activity occurs.
• The Endoplasmic Reticulum transports food and
molecules from one part of the cell to another. It
functions as the highway system of the cell.
• The Golgi apparatus unites large carbohydrate
molecules with proteins to form glycoproteins.
• Mitochondria, the powerhouses of the cell, contain
enzymes that produce energy for cellular activity.
• Lysosomes break down unwanted large molecules;
they may rupture when they are exposed to radiation, with resulting cell death.
• Ribosomes synthesize the various proteins that cells
require.
• Centrosomes contain the centrioles.
• The nucleus controls cell division, multiplication,
and biochemical reactions.
• Somatic cells divide through the process of mitosis.
• The cellular life cycle has four distinct phases: preDNA synthesis, actual DNA synthesis, post-DNA
manufacturing, and division (mitosis).
• Mitosis has four subphases: prophase, metaphase,
anaphase, and telophase.
• Genetic cells divide through meiosis.
• Meiosis is similar to mitosis, except no DNA replication occurs in telophase; the number of chromosomes in the daughter cell is reduced to half the
number of chromosomes in the parent cell.
GENERAL DISCUSSION QUESTIONS
1. What are the essential functions of water in the hu-
man body?
2. What role do antibodies fulfill for the human body?
3. Describe the structure of a DNA (deoxyribonucleic)
macromolecule.
4. Name the four nitrogenous base pairs in a DNA
macromolecule.
5. How do genes control the formation of proteins in
every cell?
6. Describe the Human Genome Project and explain
the progress that has been made as a result of the
project.
7. Why is potassium of primary importance to the hu-
man body?
8. List the components of the normal cell, and explain
their function.
9. Describe the processes of mitosis and meiosis.
10. How can multiple births occur from one preg-
nancy?
11. What is the period of cell growth that occurs before
actual mitosis called?
12. What are centrioles, and what is their function in
the human cell?
110
CHAPTER 6 Overview of Cell Biology
REVIEW QUESTIONS
1. In a DNA macromolecule, the sequence of ______
determines the characteristics of every living thing.
A. Sugars
B. Phosphates
C. Nitrogenous organic bases
D. Hydrogen bonds
2. How many base pairs are there in the human
genome?
A. 2.58 3 10
6
B. 90,000
C. 2.9 3 10
9
D. 20,500
3. Radiation-induced chromosome damage may be
evaluated during which of the following processes?
A. Prophase
B. Metaphase
C. Anaphase
D. Telophase
4. If exposure to ionizing radiation damages the
components involved in molecular synthesis beyond
repair, cells do which of the following?
A. Continue to function normally
B. Function abnormally or die
C. Repair themselves immediately because of the
enzymatic proteins they contain
D. Reproduce themselves in pairs
5. Which of the following produces antibodies?
A. Erythrocytes
B. Lymphocytes
C. Thrombocytes
D. Platelets
6. Water comprises approximately _______ of the
weight of the human body.
A. 50% to 55%
B. 60% to 70%
C. 80% to 85%
D. 90% to 95%
7. Which of the following must the human body
provide to ensure efficient cell operation?
1. Food as a source of raw material for the release
of energy
2. Oxygen to help break down food
3. Water to transport inorganic substances into
and out of the cell
A. 1 and 2 only
B. 1 and 3 only
C. 2 and 3 only
D. 1, 2, and 3
8. Which human cell component controls cell division
and multiplication as well as biochemical reactions
that occur within the cell?
A. Endoplasmic reticulum
B. Mitochondria
C. Lysosomes
D. Nucleus
9. What term is used to describe chemical secretions
that are manufactured by various endocrine glands
and carried by the bloodstream to influence the
activities of other parts of the body?
A. Amino acids
B. Antibodies
C. Hormones
D. Disaccharides
10. Somatic cells divide through the process of:
A. Meiosis
B. Mitosis
C. Mapping
D. Metabolism
Molecular and Cellular Radiation Biology
O B J E C T I V E S
After completing this chapter, the reader will be able to
perform the following:
• Define all key terms.
• Explain in what manner ionizing radiation damages
living systems.
• List three characteristics of ionizing radiation that
determine the extent to which different radiation
modalities transfer energy into biologic tissue.
• List the three radiation energy transfer determinants,
and explain their concepts.
• Explain why x-rays and gamma rays can also be
referred to as a stream of particles called photons.
• Differentiate among the three levels of biologic
damage that may occur in living systems as a result
of exposure to ionizing radiation and describe how
the process of direct and indirect action of ionizing
radiation on the molecular structure of living systems occurs.
7
• Create a diagram to illustrate the various effects
of ionizing radiation on a DNA macromolecule,
and describe the effects of ionizing radiation on
chromosomes, various types of cells, and ultimately
the entire human body.
• Explain the target theory.
• List and explain six effects of irradiation on the
entire cell that can result from damage to the cell’s
nucleus.
• Explain the purpose and function of survival curves
for mammalian cells.
• List the factors that affect cell radiosensitivity.
• State and describe the law of Bergonié and
Tribondeau.
• Describe the effects of ionizing radiation on human
blood cells, epithelial tissue, muscle tissue, nervous
tissue, and male and female reproductive cells.
C H A P T E R O U T L I N E
Ionizing Radiation
Radiation Energy Transfer Determinants
Linear Energy Transfer
Relative Biologic Effectiveness
Oxygen Enhancement Ratio
Molecular Effects of Irradiation
Effects of Irradiation on Somatic and
Genetic Cells
Classification of Ionizing Radiation Interaction
Direct Action Characteristics
Radiolysis of Water
Indirect Action Characteristics
Specific Effects of Ionizing Radiation on DNA
Effects of Ionizing Radiation on
Chromosomes
Target Theory
Effects of Irradiation on the Entire Cell
Instant Death
Reproductive Death
Apoptosis
Mitotic Death
Mitotic Delay
Interference with Function
Survival Curves for Mammalian Cells
Cell Radiosensitivity
Cell Maturity and Specialization
Oxygen Enhancement Effects
Law of Bergonié and Tribondeau
Effects of Ionizing Radiation on Human Cells and
Tissues
Summary
111
112
CHAPTER 7 Molecular and Cellular Radiation Biology
K E Y T E R M S
apoptosis
cell survival curve
chromosome breakage
direct action
free radicals
indirect action
law of Bergonié and Tribondeau
linear energy transfer (LET)
mutation
oxygen enhancement ratio (OER)
point lesion
radiation weighting factor (WR)
radiolysis
relative biologic effectiveness
(RBE)
target theory
wave-particle duality
Radiation biology, also known as Radiobiology, is the
branch of biology concerned with the effects of ionizing
radiation on living systems. Areas of study included in
this discipline are:
• The sequence of events occurring after the absorption
of energy from ionizing radiation
• The action of the living system to compensate for
the consequences of this energy assimilation
• Injury to the living system that may occur from
irradiation
The human body is a complex interconnected living
system composed of very large numbers of various
types of cells, most of which may be damaged by
radiation. Because the potentially harmful effects of
ionizing radiation on living systems occur primarily
at the cellular level, the preceding chapter placed a
strong emphasis on the basics of cell structure, composition, and function. This chapter provides an introduction to those aspects of molecular and cellular
radiation biology that are relevant to the subject of
radiation protection.
IONIZING RADIATION
Ionizing radiation damages living systems by removing
electrons from (ionizing) the atoms comprising the
molecular structures of these systems. X-ray and
gamma-ray photons can impart energy to orbital electrons in atoms if the photons happen to pass near the
electrons. High-energy charged particles such as alpha
and beta particles and protons also may ionize atoms by
interacting electromagnetically with orbital electrons.
The alpha particle, which is composed of two protons
and two neutrons and therefore carries an electric
charge of 12, strongly attracts the negatively charged
electrons as it passes.
Biologic damage, then, begins with the ionization of
atoms caused by various types of radiation. Such altered
atoms do not bond properly in molecules. If the molecule in question is necessary for the normal function of
an organism, then the entire organism may be adversely
affected.
RADIATION ENERGY TRANSFER DETERMINANTS
The characteristics of ionizing radiation vary among
different types of radiation. Characteristics include:
• Charge
• Mass
• Energy
These attributes determine the extent to which different radiation modalities transfer energy into biologic
tissue. To be able to understand how ionizing radiation
causes injury and how the effects can vary in biologic
tissue, three essential concepts must be studied:
1. Linear energy transfer
2. Relative biologic effectiveness
3. Oxygen enhancement ratio
Linear Energy Transfer
When passing through a medium such as human tissue,
ionizing radiation may interact with that medium
during its passage, and as a result, lose energy along
its path (called a track). The average energy deposited
per unit length of track is linear energy transfer (LET)
(Fig. 7.1). This energy average is calculated by dividing
the total energy deposited in the medium by the total
length of the track. LET is generally described in units
of kiloelectron volts (keV) per micron (1 micron [µm]
5 1026 m). The rate of transfer of energy from ionizing
radiation, used for diagnostic purposes (x-rays), to soft
CHAPTER 7 Molecular and Cellular Radiation Biology
113
Path of
electron
E = 350 keV
Fig. 7.1 Linear energy transfer. An electron with energy (E) of
350 keV interacts in a tissue-like material. Its actual path is tortuous, changing direction a number of times, as the electron interacts with atoms of the material via excitations and ionizations. As interactions reduce the energy of the electron through
excitation and ionization, the electron’s energy is transferred to
the material. The interactions that take place along the path of
the particle may be summarized as specific ionization (SI; ion
pairs/cm) or as linear energy transfer (LET; keV/cm) along the
straight-line continuation of the particle’s trajectory beyond its
point of entry. (From Hendee WR, Ritenour ER: Medical imaging
physics, ed 4, Chicago, 2002, John Wiley & Sons.)
SI
(IP/cm)
7
—— 1 cm
8 200
—— 2 cm
9 250
—— 3 cm
Avg. ~8.3 Avg. ~208
LET
keV/cm
100
biologic tissue is estimated to be 3 keV/µm, which is
considered to be relatively low-LET radiation compared
with other types of radiation, which can have values in
the megaelectron volt per micron (MeV/µm). Because
the amount of ionization produced in an irradiated
object is related to the amount of energy it absorbs,
and because both chemical and biologic effects in tissue
coincide with the degree of ionization experienced by
the tissue, the LET value of the radiation involved is
an essential factor in assessing potential tissue and
organ damage from exposure to that type of ionizing
radiation. When LET increases, the chance of a significant biologic response in the radiosensitive DNA macromolecule also increases.
Radiation Categories According to Linear Energy Transfer. Radiation may be divided into two general
categories according to its LET (Box 7.1), low or high.
BOX 7.1 General Categories of Linear
Energy Transfer Radiation (LET)
Low-LET Radiation High-LET Radiation
Gamma rays Alpha particles
X-rays
Electrons
Ions of heavy nuclei
Charged particles released
from interactions between
neutrons and atoms
Low-energy neutrons
Low–linear energy transfer radiation. Low-LET
radiation is electromagnetic radiation, such as:
• X-rays
• Gamma rays (short-wavelength, high-energy waves
emitted by the nuclei of radioactive substances)
Because of a property known as wave-particle dual-
ity, x-rays and gamma rays, as described in Box 2.1 in
Chapter 2 and Appendix E, can also be referred to as
streams of moving particles called photons, each of
which has no mass* and no charge.
Although electromagnetic radiation (EMR) can be
quite penetrating, it is sparsely ionizing and interacts
randomly along the length of its track. Consequently,
EMR photons do not relinquish all their energy
quickly. When low-LET radiation interacts with biologic tissue, it causes damage to a cell primarily
through an indirect action that involves the production
of molecules called free radicals. These are solitary
atoms, for example, a non-molecular hydrogen atom
[H]**, or most often a combination of atoms such as
[OH] that behave as single entities and are chemically
reactive as a result of the presence of unpaired valence
(outermost) electrons. Also, but much less likely, the
low-LET radiation may directly induce single-strand
breaks in the ladder-like DNA structure. Because lowLET radiation generally causes sub-lethal damage to
DNA, repair enzymes can usually reverse the cellular
damage.
*More precisely the photon has zero rest mass or intrinsic
mass. The photon, however, has motional mass associated with
its total energy E and this quantity is related to its non-rest
mass by Einstein’s equation: E5mc2.
**Hydrogen atoms normally occur as bound molecular pairs
H2 and not as individual atoms.
114
CHAPTER 7 Molecular and Cellular Radiation Biology
High–linear energy transfer radiation. High-LET
radiation includes particles that possess substantial:
mass and charge.
This type of radiation, unlike low-LET radiation,
can produce dense ionization along its path and therefore is much more likely to interact significantly with
biologic tissue. Some typical examples of high-LET
radiation are:
• Alpha particles
• Ions of heavy nuclei
• Charged particles released from interactions between
neutrons and atoms
Low-energy neutrons, which carry no electrical
charge, are also a form of high-LET radiation. Since
these types of high-LET radiation exhaust their energy
rapidly in matter, unless they are of extremely high
energies, they cannot travel or penetrate as far as x-ray
and gamma ray photons. Even so, high-LET radiation
can be very destructive to biologic matter.
Risk of damage to DNA. Fig. 7.2 demonstrates
an electron and an alpha particle passing through the
nucleus of a cell in the vicinity of a strand of DNA. The
size of the entire area is only approximately 10 nanometers (10 billionths of a meter). The electron is most
often a Compton scattered electron, whereas the alpha
particle represents one of the particles ejected from
the nucleus of an atom after radioactive decay of an
element such as radon.
Probability of interaction with DNA. As exhibited
in Fig. 7.2, there are many more alpha particle interactions in the small region than electron interactions, the
alpha particle is 1000 times the LET of the electron.
Each time the particle interacts, it loses some energy
and slows down in the cell. When enough interactions
have occurred, the particle will essentially be at rest,
and interactions beyond this path penetration are
unlikely. Because it does not interact as often, the
electron, however, can travel significantly farther than
the alpha particle. A Compton scattered electron or
photoelectron set in motion in a patient exposed to
diagnostic x-rays may travel through thousands of
cells, having interactions in only some of them and
with a low probability that any of these will occur in
the DNA. Conversely, an alpha particle, such as the one
~10 nanometers
S
<
e
S
P
S
P
S
P
S
S
P
S
P
S
P
S
A~T
P
S
A~T
P
P
C~G
S
P
A~T
G~C
A~T
S
P
S
P
P
S
P
S
P
S
LET~0.25 keV
+m
T~A
G~C
T~A
C~G
C~G
P
S
P
T~A
C~G
A~T
G~C
T~A
++
∝
P
S
S
P
S
S
P
S
S
P
S
P
S
P
S
T~A
G~C
P
T~A
C~G
C~G
P
S
P
C~G
A~T
P
G~C
T~A
~10 nanometers
A~T
C~G
A~T
A~T
G~C
T~A
A B
Fig. 7.2 An electron and an alpha particle passing through the nucleus of a cell near a strand of DNA. (A) For
an electron, several interactions may occur in the vicinity of a DNA strand and create a risk of damage to the
DNA. (B) Because many interactions may occur in the vicinity of a DNA strand, some damage is likely.
S
A~T
P
S
P
S
P
S
P
P
S
P
S
P
S
LET~250 keV
+m
CHAPTER 7 Molecular and Cellular Radiation Biology
115
shown, may travel through only a few cells, but will have
a high probability of interacting with the DNA of a cell
it encounters.
High–linear energy transfer radiation and internal
contamination. For radiation protection, high-LET
radiation is of most significant concern when internal
contamination is possible, that is, when a radionuclide
has been:
• Implanted
• Ingested
• Injected
• Inhaled
Then, the potential exists for irreparable damage
because, with high-LET radiation, multiple-strand
breaks in DNA are possible. For example, with a doublestrand break in the same rung of the DNA ladder-like
structure, complete chromosome breakage occurs (see
Fig. 7.8A). Repair enzymes are incapable of undoing
this damage, and hence cell death will most likely follow.
Relative Biologic Effectiveness
Biologic damage produced by radiation escalates as
the LET of radiation increases. Identical doses of
radiation of different LETs do not render identical
biologic effects. Relative biologic effectiveness (RBE)
describes the comparative capabilities of radiation
with differing LETs to produce a particular biologic
reaction. RBE of the type of radiation used is the ratio
of the dose of a reference radiation (conventionally
250-kVp x-rays, where kVp is optimal peak kilovoltage) to the dose of radiation of the type in question
that is necessary to produce the same biologic reaction
in a given experiment. The response is what is produced by a dose of the test radiation delivered under
the same conditions. Box 7.2 demonstrates the mathematical expression of RBE.
Use of the Relative Biologic Effectiveness Concept
for Specific Experiments. The concept of RBE refers
to specific experiments with specific cells or animal
tissues (e.g., tumor cells in a Petri dish, skin of the left
hand of a particular strain of laboratory rat). Because
the various types of cells or tissues differ in their biologic response per unit quantity of absorbed dose,
the concept of RBE alone is not practical for specifying
radiation protection dose levels in humans. To overcome this limitation, a radiation weighting factor (WR)
is employed to calculate the equivalent dose (EqD) to
BOX 7.2 Mathematical Expression of
Relative Biologic Effectiveness (RBE)
Dose in Gy from 250 kVp x-rays
RBE
5
Dose in Gy of test
Example: A biologic reaction is produced by 2 Gyt of
a test radiation. It takes 10 Gy
produce the same biologic reaction. What is the RBE
of the test radiation?
The RBE is 5, which means that the test radiation is five
times as effective in producing this biologic reaction as
are 250-kVp x-rays.
t
(reference radiation)
t
10
2
radiation
of 250-kVp x-rays to
t
55
determine the ability of a dose of any kind of ionizing
radiation to cause biologic damage. The WR values are
similar to the values of RBE for any particular type of
radiation. For example, the WR for x-radiation is 1, and
the RBE for diagnostic x-rays is also 1. The WR values
for different types of ionizing radiation are listed in
Table 4.2 in Chapter 4.
Oxygen Enhancement Ratio
The Oxygen Enhancement Ratio (OER), or oxygen
effect, refers to the enhancement of the therapeutic
or detrimental effect of ionizing radiation due to the
presence of oxygen. When tissue is irradiated in an oxygenated state, the tissue is more sensitive to radiation
than when it is exposed to radiation under anoxic
(without oxygen) or hypoxic (low oxygen) conditions.
This is an essential concept in radiation therapy. Cells
that are anoxic during irradiation are about three
times more resistant than cells that are well oxygenated
at the time of irradiation. The OER describes this effect
numerically.
The OER is the ratio of the radiation dose required
to cause a particular biologic response of cells in an
oxygen-deprived environment to the radiation dose
required to generate an identical response under normal oxygenated conditions. The OER formula is stated
in Box 7.3.
In general, x-rays and gamma rays, which are lowLET types of radiation, have an OER of approximately
3.0 when the radiation dose is high. The OER may be
less (approximately 2.0) when radiation doses are lower
1,2
116
CHAPTER 7 Molecular and Cellular Radiation Biology
BOX 7.3 Oxygen Enhancement Ratio
(OER)
Radiation dose required to
OER
cause5biologic response without O
Radiation
cause biologic response w
dose required to
iith O
2
2
than 2 Gyt. This surprising result exists because a 2 Gyt
dose is associated with the linear (i.e., straight-line)
portion of the linear-quadratic dose–response relationship for cell killing (see Fig. 9.3), whereas higher doses
can fall on the curved (i.e., quadratic) portion of
the dose–response curve.3 The term linear-quadratic
indicates that the equation that best fits the data has
conditions that depend on dose (linear dependency)
and dose squared (quadratic dependence). Because
high-LET radiation, such as alpha particles, produces its
biologic effects from direct action—namely, direct ionization and disruption of biomolecules—the presence
or absence of oxygen is of little or no consequence to
their effects. Therefore, the OER of high-LET radiation
is approximately equal to 1. For low-LET radiation,
a significant fraction of bioeffects are caused by indirect
actions in which a free radical is formed. Because
of their high reactivity, free radicals can dramatically
increase the amount of biologic damage. Oxygen, if
present in biologic tissues, will react with these chemical
entities to produce organic peroxide compounds.* The
latter represent non-restorable changes in the chemical
composition of the target material. Without oxygen, the
damage created by the indirect action of radiation on a
biologic molecule may be repaired, but when damage
occurs through an oxygen-mediated process, the final
result is lasting or fixed. This phenomenon has been
called the oxygen fixation hypothesis.
MOLECULAR EFFECTS OF IRRADIATION
In living systems, biologic damage stemming from exposure to ionizing radiation is examined on three levels:
• Molecular
• Cellular
• Organic systems
*An organic peroxide is any organic (carbon-containing)
compound with two oxygen atoms joined together (-O-O-).
Any visible radiation-induced injuries of living
systems at the cellular or organic level always begin
with damage at the molecular level. Molecular damage
results in the formation of structurally changed molecules that may severely impair cellular function.
Effects of Irradiation on Somatic and Genetic Cells
Cells of the human body are highly specialized. Each cell
has a predetermined task to perform, and each cell’s
function is governed and defined by the structures of its
constituent molecules. Absorbed energy from ionizing
radiation can alter these structures, thereby disturbing
the cell’s chemical balance and, ultimately, how it operates. When this occurs, the cell no longer performs its
normal tasks. If sufficient quantities of somatic cells
(i.e., all cells in the body other than female and male
germ cells) are affected, entire body processes can be
disrupted. Conversely, if radiation damages the germ
(reproductive) cells, the damage may be passed on to
future generations in the form of genetic mutations.
Classification of Ionizing Radiation
Interaction
When ionizing radiation interacts with a cell, ionizations and excitations (the addition of energy to a
molecular system that raises it from a ground state to
a higher-energy, or excited, state) are produced either
in vital biologic macromolecules or in water (H2O), the
medium in which the cellular organelles are suspended.
Based on the site interaction, the effect of radiation
on the cell is classified as either (Fig. 7.3): a direct or
indirect action.
As mentioned previously, in direct action, biologic
damage occurs as a result of the ionization of atoms
on essential molecules produced by an immediate
interaction with incident radiation. Indirect action,
instead, is always a multistage process that first involves the production of free radicals that are usually
created by the interaction of the radiation with water
(H2O) molecules. These unstable agents, then, may
proceed to interact with cellular molecules. Free radicals are so highly reactive that should they encounter
DNA macromolecules, they can cause cell death.
Direct action has some probability of occurring after
exposure to any kind of radiation. However, direct
action is much more likely to occur after exposure
to high-LET radiation such as alpha particles, which