RADIOBIOLOGY
are produced and secreted by the
 Study of the effects of ionizing radiation on
biologic tissue
 Ultimate goal: to accurately describe the
effects of radiation on humans
 Dose-response relationships: develop to
predict the effects &manage accidental
exposure
 Diagnostic Radiology: concern with stochastic
effects of radiation
ATOMIC COMPOSITION
Note: Rdaiation interacts at the atomic level.
FIVE PRINCIPLE TYPES OF MOLECULES
Simple Molecules:
 Water
Macromolecules:
 Proteins
 Lipids
 Carbohydrates
 Nucleic acids
Water 
 Simplest and the most abundant molecular
constituent of the body.
 It consists of two atoms of hydrogen and one
atom of oxygen (H2O)
 constitutes 80% of human substance
 provide some form and shape
 Assist in maintaining body temperature
 Delivers energy to the target molecules
 Contribute to radiation effects
 End products of catabolism (+CO2)
 Enters into some biochemical reactions
PROTEINS
 Organic macromolecules
 Long-chain macromolecules
 15% of the molecular composition of the body
 Purpose:
o Structure & support (muscles)
 Functions as:
o Enzymes to breakdown foods in
stomach
o Hormones & Antibodies (hormones
endocrine glands)
 Note: It is an organic macromolecule because
it contains carbon and is a life sustaining
Enzymes - are molecules that are necessary in small
quantities to allow a biochemical reaction to continue
even though they do not directly enter into the
reaction
Hormones - are molecules that exercise regulatory
control over some body functions, such as growth and
development. Hormones are produced and secreted
by the endocrine glands—the pituitary, adrenal,
thyroid, parathyroid, pancreas, and gonads.
Antibodies - constitute a primary defense mechanism
of the body against infection and disease. The
molecular configuration of an antibody may be precise
and designed for attacking a particular type of invasive
or infectious agent, the antigen.
PROTEIN SYNTHESIS
 The metabolic production of proteins
 Used 22 amino acids
 A critical cellular function necessary for
survival
 Dependent on nucleic acids
 Note: occurs in much more abundance than
nucleic acids synthesis
o It is an organic macromolecule
because it contains carbon and is a
life sustaining
LIPIDS
 Composed of two kinds of smaller molecules-
glycerol and fatty acid.
 Present in all tissues of the body
 Structural component of cell membranes
 Often concentrated just under the skin that
serves a thermal insulator
 Organic macromolecules
 Found in cell membrane
 Fuel for the body by providing energy stock
 Composed of carbon, hydrogen, and oxygen
 Purpose:
o Provides fuel for the body by
providing energy stores
o Thermal insulator from the
environment
  Note: lipids can be catabolized into glucose
but with great difficulty
Protein contains carbon
Lipids life sustaining molecules
Carbohydrate
DNA (Deoxyribonucleic Acid)
 The most critical and radiosensitive target
molecule
 The command center or control molecule for
cell function
 Concentrated in the nucleus of a cell
 Contains all the hereditary information that
represents a cell or whole individual (germ
cell)
 It is the control center for life
NUCLEIC ACIDS
 The rarest, very complex and very large
macromolecule in the body
 Function:
o Growth and development of the cell
(protein synthesis)
 Two principal Nucleic Acids: DNA & RNA
o Important to cell metabolism
DNA
(adenine, thymine, cytosine, guanine)
Location: nucleus
Sugar component: deoxyribose
Base component: thymine
Configuration: double helix
RNA
(adenine, uracil, cytosine, guanine)
Location: cytoplasm nucleus (some)
Sugar component: ribose
Base component: uracil
Configuration: single helix
 Molecules that are involved in the growth and
development of a cell (protein synthesis)
 Two Types:
o Messenger RNA (mRNA)
o Transfer RNA (RNA)
CARBOHYDRATES
 also called saccharides
 composed of carbon, hydrogen, oxygen
 Function:
o To provide fuel for cell metabolism
o Monosaccharides and Disaccharides are
sugars. Polysaccharides are large and include
plant starches and animal glycogen.
o Glucose – the ultimate molecule that fuels the
body.
CELL FUNCTIONS
 Absorbs all molecular nutrients through the
cell membrane
 Purpose:
o For energy production
o For molecular synthesis (e.g protein
Synthesis)
PHYSICAL FACTORS THAT AFFECT
RADIOSENSITIVITY
 Linear Energy Transfer (LET)
 Relative Biologic
 Effectiveness (RBE)
 Protraction
 Fractionation
THE HUMAN CELL
 The principal molecular components of the
human body are made of intricate cellular
structures.
Two Major Structures of the Cell are:
Nucleus – is the principal molecular component is
DNA which the genetic material of the cell. Also
contain RNA, protein, and water.
Cytoplasm – makes up the bulk of the cell and
contains great quantities of all molecular components
except DNA.
Endoplasmic Reticulum – is a cannel or a series of
channels that allows the nucleus to communicate with
the cytoplasm.
Mitochondria – is a large bean-shaped structures. It is
called as an engine of the cell because
macromolecules are digested in the mitochondria to
produce energy for the cell.
Ribosome - are small dot-like structures which are
the site of protein synthesis and therefore are
essential to normal cellular function.
Lysosomes – are small pea-like sacs which contain
enzymes capable of digesting cellular fragments and
sometimes the cell itself. Lysosomes help to control
intracellular contaminants.
Note: they surrounded by membranes. These
membranes consist principally of lipid–protein
complexes that selectively allow small molecules and
water to diffuse from one side to the other. These
cellular membranes, of course, also provide structure
and form for the cell and its components
CELL FUNCTION
Protein synthesis is a good example of a critical
cellular function necessary for survival
Codon - a series of three base pairs that identifies one
of the 22 human amino acids available for protein
synthesis.
CELL PROLIFERATION
Two general Types of Cells
Somatic Cells – when proliferate or divide it undergo
mitosis, all other cells are somatic cells.
Genetic Cells – includes the oogonium of the female
and the spermato-gonium of the male. Genetic cells
undergo meiosis.
Mitosis
Cell biologists usually identify four phases of the cell
cycle: M, G1, S, and G2.
During prophase, the nucleus swells, and the DNA
becomes more prominent and begins to take
structural form.
At metaphase, the chromosomes appear and are
lined up along the equator of the nucleus. It is during
metaphase that mitosis can be stopped and
chromosomes can be studied carefully under the
microscope.
Anaphase is characterized by the splitting of each
chromosome at the centromere, so that a centromere
and two chromatids are connected by a fiber to the
poles of the nucleus. These poles are called spindles,
and the fibers are called spindle fibers. The number of
chromatids per centromere has been reduced by half,
and these newly formed chromosomes migrate slowly
toward the spindle.
The final segment of mitosis, telophase, is
characterized by the disappearance of structural
chromosomes into a mass of DNA and the closing off
of the nuclear membrane like a dumbbell into two
nuclei. At the same time, the cytoplasm is divided into
two equal parts, each of which accompanies one of
the new nuclei.
Cell division is now complete. The two daughter cells
look precisely the same as the parent cell and contain
exactly the same genetic material.
Interphase - the portion of the cell cycle between
mitotic events. It is the period of growth of the cell
between divisions.
Meiosis
The genetic cell begins meiosis with 46 chromosomes
that appear the same as in a somatic cell that has
completed the G2 phase. The cell then progresses
through the phases of mitosis into two daughter cells,
each containing 46 chromosomes of two chromatids
each. The names of the sub-phases are the same for
meiosis and mitosis.
Each of the daughter cells of this first division now
progresses through a second division in which all
cellular material, including chromosomes, is divided.
However, the second division is not accompanied by
an S phase. Therefore, no replication of DNA occurs;
consequently, no chromosomes are duplicated. Each
of the resulting granddaughter cells contains only 23
chromosomes.
Each parent has undergone two division processes,
which have resulted in four daughter cells. During the
second division, some chromosomal material is
exchanged among chromatids through a process
called crossing over. Crossing over results in changes
in genetic constitution and changes in inheritable
traits.
TISSUES AND ORGANS
During the development and maturation of a human avenue by which electrical impulses are transmitted
from two united genetic cells, a number of different throughout the body for control and response.
types of cells evolve. Collections of cells of similar
When these various types of tissue are combined to
structure and function form tissues.
form an organ, they are identified according to two
These tissues in turn are precisely bound together to parts of the organ. Whereas the parenchymal part
form organs. The tissues and the organs of the body contains tissues that represent that particular organ,
serve as discrete units with specific functional the stromal part is composed of connective tissue and
responsibilities. Some tissues and organs combine into vasculature that provide structure to the organ.
an overall integrated organization known as an organ
The deterministic effects of high-dose radiation may
system. The principal organ systems of the body are
include observable organ damage. The various organs
the nervous system, digestive system, endocrine
of the body exhibit a wide range of sensitivity to
system, respiratory system, and reproductive system.
radiation. This radio sensitivity is determined by the
Effects of radiation that appear at the whole-body
function of the organ in the body, the rate at which
level result from damage to these organ systems that
cells mature within the organ, and the inherent radio
occurs as the result of radiation injury to the cells of
sensitivity of the cell type.
that system.
Precise knowledge of these various organ radio
The cells of a tissue system are identified by their rate
sensitivities is unnecessary; however, knowledge of
of proliferation and their stage of development.
general levels of radio sensitivity is helpful toward
Immature cells are called undifferentiated cells,
understanding the effects of whole-body radiation
precursor cells, or stem cells. As a cell matures
exposure, particularly in the acute radiation syndrome
through growth and proliferation, it can pass through
(Table 29-3).
various stages of differentiation into a fully functional
and mature cell.

Stem cells are more sensitive to radiation than mature

cells.

The sensitivity of the cell to radiation is determined

somewhat by its state of maturity and its functional
role. Table 29-2 lists a number of different types of
cells in the body according to their degree of radio
sensitivity. The tissues and organs of the body include
both stem cells and mature cells. Several types of
tissue can be classified according to structural or
functional features. These features influence the
degree of radio sensitivity of the tissue. Epithelium is
the covering tissue, and it lines all exposed surfaces of
the body, both exterior and interior. Epithelium
covers the skin, blood vessels, abdominal and chest
cavities, and gastrointestinal tract

Connective and supporting tissues are high in protein

and are composed principally of fibers that are usually
highly elastic. Connective tissue binds tissues and
organs together. Bone ligaments and cartilage are
examples of connective tissue.

Muscle is a special type of tissue that can contract. It

is found throughout the body and is high in protein
content.

Nervous tissue consists of specialized cells called

neurons that have long, thin extensions from the cell
to distant parts of the body. Nervous tissue is the
  Provides the basis for radiation control
activities
Two Characteristics:
 Threshold or Non-Threshold
 Linear or Non-Linear (S-TYPE)

Linear Dose Response Relationship

 The response is directly proportionate to the
does
 Lower Dose: lower response
 Higher Dose: higher response

Non-Linear Dose Relationship

 The response is not directly proportional to
the dose
 Variable responses from variable doses
 Low Dose: variable response
 High Dose: variable response

Threshold Dose Response Relationship

 The level below which there is no response
At Dt: the threshold dose
- Intersects the dose axis greater than zero
Below Dt: no response is observed

Note: 2GYT = Death

DOSE-RESPONSE RELATIONSHIPS
Important Applications:
 Used to design therapeutic treatment
routines for patient with cancer

Linear-Non Threshold Relationship
 Basis for radiation protection guidelines
 Basis for current dose limits
 The results of extrapolation
 Radiation-induced cancer
 Single-hit chromosomes aberration
 Stochastic Effects of Radiation
- Radiation-induced leukemia
- radiation induced genetic effect/damage
- Radiation-induced malignant disease
- Radiation-induced thyroid cancer
- Radiation-induced life-span shortening
- Chronic Lymphocytic leukemia
Nonlinear-Non Threshold Relationship
 Multihit Chromosome Aberration
Nonlinear Threshold
 Deterministic Effects of Radiation
- Radiation-induced cataracts
- Acute radiation syndrome
- Radiation-induced death
- Skin effects from high-dose fluoroscopy
IRRADIATION OF MACROMOLECULES
1. Main-chain scission (hati-hatiin)
▪ breakage of the backbone of the
long chain macromolecule
▪ result is reduction of a long,
single molecule into many
smaller molecules, each may still
be macromolecular
▪ decrease viscosity
- viscous solution is very thick and slow
to flow
2. Cross-linking
▪ Process of side spurs created by irradiation &
attached to a neighboring macromolecule or
to another segment of the same molecule
▪ Result in increased viscosity of a
macromolecular solution
3. Point lesion
▪ Radiation interaction with
macromolecules that result in disruption
of single chemical bonds
▪ Impairment or loss of function at the
point of a single chemical bond
▪ Not detectable but they can cause a
minor modification of the molecule,
which in turn can cause it to malfunction
within the cell
▪ Can be produced by free radicals
EFFECTS OF RADIATION DAMAGED TO DNA
 DNA is the most important molecule in the
human body because it contains the genetic
information of each cell (target molecule)
• Not abundant in the cell
• Inside the nucleus
• in the form of chromosomes
• most radiosensitive molecule
• If radiation damage is severe enough, visible
chromosomes aberrations may be detected
• It is reversible, it can heal itself
Chromosomes – control the growth and
development of the cell, determines the
characteristics of individuals
Radiation-damaged human chromosomes
1. Terminal deletion – there is missing
end part
 2. Dicentric formation – 2 centers
3. Ring formation – it forms circular
shape
• Damage to DNA can also result to abnormal
metabolic activity
• Uncontrolled rapid proliferation of cells is the
principal characteristics of radiation-induced
malignant disease
• If damage to DNA occurs within a germ cell,
then it is possible that the response to
radiation will not be observed until the
following generation (cause of genetic effect)
Germ cell - are the only cells in the body that
have half the amount of chromosomes,
undergo both mitosis and meiosis and in
males produce the gamete, sperm.
GROSS STRUCTURAL RADIATION RESPONSE TO
DNA
• main-chain scission with only one side rail
severed
• main-chain scission with both side rails
severed
• main-chain scission and subsequent cross-
linking
• rung breakage causing a separation of bases
• change in or loss of a base
 all DNA response are reversible except for
change in or loss of base
 genetic mutation – damage which the
sequence of bases was altered, therefore, the
triplet code of codons may not remain intact
Point mutation
• type of radiation damage, molecular lesion
which can be minor or major importance to
the cell
• critical because of transfer of the incorrect
genetic code to one of the two daughter
cells (through mitosis, typical in tissue
growth)
3 principal observable effects that may result from
irradiation of DNA
1. Cell death
2. Malignant disease
3. Genetic Damage
Radiolysis of Water
• dissociates into other molecular products, as a
result of irradiation is called radiolysis of
water.
• When an atom of water (H2O) is irradiated, it
is ionized and dissociates into two ions (ion
pair)
• Number of electron is equal to number of
proton in periodic table
After initial ionization, a number of reactions can
happen.
1. Ion pair may rejoin a stable water molecule – no
damage occurs
2. If these ions do not rejoin, negative ion (electron)
attach to another water molecule which produce a
third type of ion
▪ HOH+ and HOH- ions are relatively
unstable and can dissociate again into
small molecules
▪ HOH+ = H+ + HO
 ▪ HOH- = OH- + H
▪ The final result of the radiolysis of
water is the formation of an ion pair
(H+ and OH-) which are free radicals
▪ It can be recombined and no
biologic damage would occur, not
unusual
Free Radical
• uncharged molecule that contains a single
unpaired electron in the outer shell
• they are highly reactive o unstable, lifetime of
less than 1 ms
• but they are capable of diffusion through the
cell and interact even at distant site
• they contain excess energy than can be
transferred to other molecule to disrupt
bonds and produce point lesion at some
distance from the initial ionizing event
Hydrogen Peroxide
• OH* free radical joined with similar molecule
• H2O2 Poisonous to the cell, toxic agent
• per- prefix, meaning one more oxygen than
the -ate.
Hydroperoxyl Formation
• considered to be the principal damaging
product after radiolysis of water
• H* + O2 = HO*2
• Formed by interaction of H* and molecular
oxygen
• two hydroperoxyl molecule can form
hydrogen peroxide
effects of irradiation in vivo result from
indirect effect TARGET THEORY
 cell contains many species of molecules
 radiation damage to such molecules probably
would not result in noticeable injury to the
cell because similar molecules would be
available to continue to support the cell
 some molecules in the cell are considered
necessary for normal cell function
 these molecules are not abundant, may be
only one such molecule
 radiation damage to such a molecule could
affect the cell severely because no similar
molecules would be available for substitute
 DNA is the target molecule
The three main functions of DNA are as follows.
1. to form proteins and RNA
2. to exchange the genetic material of parental
chromosomes during meiotic cell division
3. to facilitate occurring mutations and even
mutational change in a single nucleotide pair, called
point mutation
Target theory - for a cell to die after radiation
exposure, its target molecule must be inactivated
- when radiation does interact with the
target, a hit is said to have occurred
- radiation interaction with molecules
other than the target molecule also can result
in a hit
- it is not possible to distinguish
between a direct and an indirect hit

Direct and Indirect Effects

• in vivo, when biologic material is irradiated,
harmful effects damage the DNA particularly
Direct effect - ionization of the target molecule

Indirect effect - ionization at a distant, at a

noncritical molecule, which then transfers the
energy to the target molecule. Ex. free radical
as intermediate molecule

 it is not possible to determine which affect

the target molecule, whether direct or
indirect
 human body consists of approx. 80% water
and less than 1% DNA concluded that all
  Fractionation – reduces effect because cells
undergo repair and recovery between doses,
used in radiation oncology

Biologic Factors That Affect Radiosensitivity

 Oxygen Effect - tissue is more sensitive to
radiation when irradiated in the
oxygen/aerobic state than under anoxic or
hypoxic conditions
• Age – humans are more sensitive before birth and
FUNDAMENTAL PRINCIPLES OF old age
RADIOBIOLOGY
• Recovery – human cells can recover from radiation
damage if the dose is
Law of Bergonie and Tribondeau
not sufficient to kill the cell before its next cell division
 Two French scientists
(interphase death)
 Theorized that radiosensitivity was a function
of the metabolic state of the tissue being • Chemical Agents
irradiated
- Radiosensitizers – enhance the effect of
 Radiosensitivity of living tissue varies with
radiation. Ex. Halogenated pyrimidines.
maturation and metabolism
Methotrexate, actinomycin D, hydroxyurea,
vitk
- Hormesis – low dose effect is good for you

Physical Factors That Affect Radiosensitivity

 The response of the tissue is determined
principally by the amount of energy deposited
per unit of mass (Gyt or rad)

Linear Energy Transfer

 measure of the rate at which energy is
transferred from ionizing radiation to soft
tissue
 ability of ionizing radiation to produce a
biologic response increase as LET increase,
increase probability of interaction with the
target molecule

Relative Biologic Effectiveness

 LET increase, biologic damage increase
 Quantitatively described by RBE

Protraction and Fractionation

 Dose of radiation is delivered over a long
period of time rather than quickly, effect of
dose is less
 Protraction - Dose is delivered continuously
but lower (last a long time),
 CELL-SURVIVAL KINETICS
 Single-Target, Single-Hit
Model: Biologic Targets (bacteria)
 Multitarget, Single-Hit Model: Human Cells-
Dose Threshold
 Random rain drops and ratio of wet to dry
squares
 Increased # or drops = decreased # of dry
squares
 After irradiation of 100 cells, the dose-
response is exponential D37 is the dose that
CELLULAR RADIOBIOLOGY results in 37% survival.

Target Theory
 DNA is the target molecule.
 According to the target theory, for a cell to die
after radiation exposure, its target molecule
must be inactivated

CELL-SURVIVAL KINETICS CONT.

 Low D37 = High radio sensitivity (more
surviving cells)
 Split squares require both halves to be hit for
square to be wet
HITS  Multitarget, single hit model of cell survival is
 LOW LET & OER = low probability of target characterized of human cells
hits  Do is mean lethal dose; Dq is threshold dose
 O2 presence = free radicals and increased
volume leading to an increased hit probability
 High LET = close ionizations and an increased
hit probability
 O2 presence = no extra hits; max # hits there
with direct and high LET

RECOVERY
 Some damage must be accumulated before
the cell dies; this is called sub lethal damage
 The wider the shoulder of the graph, the more
sublethal damage
  For full recovery, the time between each split
cell dose must be at least as long as the cell
generation time, usually 24 hrs.
 G1 is the most time variable of the cell phases
 Human cells are most radiosensitive in M
phase and most radiosensitive in late S

Split-Dose Irradiation

RBE AND OER

 O2 presence maximizes the effect of low-LET
radiation
 High-LET show little difference with O2
presence