PART I: HUMAN BIOLOGY The ultimate goal of radio biologic research is to

accurately describe the effects of radiation on humans so

HUMAN RADIATION RESPONSE that radiation can be use more safely in diagnosis and
more effectively in therapy. Most radio biologic research
HUMAN RESPONSES OF RADIATION ON
HUMANS seeks to develop radiation dose-response relationships to
DETERMINISTIC EFFECTS OF RADIATION ON the effects of planned doses can be predicted and the
HUMANS response to accidental exposure managed.

1. Acute Radiation Syndrome COMPOSITION OF THE BODY

a. Hematologic Syndrome
b. Gastrointestinal Syndrome The human body is composed of atoms; radiation
c. Central Nervous System Syndrome interacts at the atomic level. The atomic composition of
the body determines the character and degree of the
2. Local Tissue Damage radiation interaction that occurs.
a. Skin
b. Gonads 85% of the body consists of hydrogen and oxygen
c. Extremities
3. Hematologic Depression Atomic Composition of the Body
4. Cytogenetic Damage 60% Hydrogen 0.2% Calcium
25.7% Oxygen 0.1% Phosphorus
STOCHASTIC EFFECTS OF RADIATION ON 10.7% Carbon 0.1% Sulfur
HUMANS 2.4% Nitrogen 0.8% Trace Elements

1. Leukemia
2. Other malignant disease CELL THEORY
a. Bone Cancer
b. Lung Cancer Robert Hooke (1665)
c. Thyroid Cancer
d. Breast Cancer - An English school master first named the cell, as
3. Local Tissue Damage the biologic building block.
a. Skin
b. Gonads Anton Van Leeuwenhock (1673)
c. Eyes
4. Shortening of Life Span - He accurately described a living cell on the basis
5. Genetic Damage of his microscopic observations.
a. Cytogenetic Damage
b. Doubling Dose Schneider and Schwann (1838)
c. Genetically Significant Dose
- Showed conclusively that in all plants and
EFFECTS OF FETAL IRRADIATION animals, cells are the basic functional units. This
1. Prenatal Death is the cell theory.
2. Neonatal Death
3. Congenital Malformation Watson and Crick (1953)
4. Childhood Malignancy
5. Diminished growth and development - Description of molecular structure of
deoxyribonucleic acid (DNA) as the genetic
substance of the cell was a major
Deterministic Effect accomplishment.

- If the radiation response is increases in severity MOLECULAR COMPOSITION

with increasing radiation dose
Five principal types of molecules are found in the body.
- Occurs within days after the radiation exposure
Four of these molecules- proteins, lipids (fats),
Stochastic Effect carbohydrates (sugar and startches), and nucleic acids-
are macromolecules
- If the incidence of the radiation response
increases with increasing radiation dose. Molecular composition of the body
- It is not observed for months and years. 80% water 1% carbohydrates
15% protein 1% Nucleic Acid
Radiobiology 2% lipids 1% other
Macromolecules
- Is the study of the effects of ionizing radiation
on biologic tissue - Are very large molecules that sometimes consist
of hundreds of thousands of atom

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Principal Classes of Organic Molecules
- Proteins
- Lipids
- Carbohydrates
DNA
- Considered to be the most critical and
radiosensitive target molecule.
Water
- Most abundant molecule in the body, and it is
the simplest
- Plays an important role in delivering energy to
the target molecule, thereby contributing the
radiation effects.
- It consists of two atoms of hydrogen and one
atom of oxygen, and constitutes approximately
80% of human substance.
Homeostasis
- It is the concept of the relative constancy of the
internal environment of the human body
Catabolism
- Breaking down into smaller units
- Water and carbon dioxide are the end product in
the catabolism of macromolecules.
Anabolism
- The production of large molecules from small
Proteins
- 15% molecular composition of the body
- Long chain of macromolecules that consists of a
linear sequence of amino acids connected by
peptide bonds.
- Twenty-two amino acids are used in protein
synthesis, the metabolic production of proteins.
- The generalized formula for a protein is
C n H n On N n T n , where the subscript “n” refers
to the number of atoms of each element in the
molecule; T represents trace element. In general,
50% of the mass of a protein molecule is carbon,
20% oxygen, 17% nitrogen, 7% hydrogen, and
6% other elements
Enzyme
- They 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
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Hormones
- They are molecules that exercise regulatory
control over some body functions, such as
growth and development.
- They are produce and secreted by the endocrine
glands- the pituitary, adrenal, thyroid,
parathyroid, pancreas and gonads
Antibodies
- Constitutes a primary defense mechanism of the
body against infection and disease
Lipids
- They are organic molecules composed solely of
carbon, hydrogen, and oxygen.
- It is represented by the general formula C n H n
O n.
- In general, lipids are composed of two types of
smaller molecules- glycerol and fatty acid.
- Each lipid is composed of one molecule of
glycerol and three molecules of fatty acid.
- Lipids serve as a thermal insulator from the
environment. And also serve as fuel for the body
by providing energy stores.
Carbohydrates
- Similar to lipids, are composed of carbon,
hydrogen, and oxygen, but their structure is
different. This structural difference determines
the contribution of the carbohydrate molecule to
body biochemistry. The ratio of the number of
hydrogen atoms to oxygen atoms in a
carbohydrate molecule is 2:1 (as in water) and a
large fraction of these molecules consists of
these atoms.
- Carbohydrates were first considered to be
watered, or hydrated, carbons, hence their name.
- Carbohydrates are also called saccharides.
Monosaccharides and disaccharides are sugars.
The chemical formula for glucose, a simple
sugar, isC 12 H 12 O6. Polysaccharides are large
and include plant starches and animal glycogen.
The chemical formula for polysaccharide is
(C ¿ ¿ 6 H 10 O5) n ¿, where n is the number of
simple sugar molecules in the macromolecule.
- The chief function of carbohydrates in the body
is to provide fuel for cell metabolism
Glucose
- It is the ultimate molecule that fuels the body
Nucleic acid
- Two principal nucleic acids are important to
human metabolism: deoxyribonucleic acid
 (DNA) and ribonucleic acid (RNA). Located
principally in the nucleus of the cell.
DNA
- Serve as the command or control molecule for
cell function
- It contains all the hereditary information that
represents a cell
- It principally located in the cytoplasm
- Double-helix configuration
RNA
- Also found in the nucleus
- Two types of RNA have been identified:
messenger RNA and transfer RNA
Attached to each deoxyribose molecules is one of four
different nitrogen-containing or nitrogenous organic
bases: adenine, guanine, thymine, or cytosine.
Adenine and Guanine are purines, thymine and cytosine
are pyrimidines
Nucleotides
- Base sugar-phosphate combination
NOTE: Only Adenine-thymine and Cytosine-guanine
base bonding is possible in DNA
RNA
- The sugar content is ribose rather that
deoxyribose, and uracil replaces thymine as a
base component.
- RNA form a single helix
THE HUMAN CELL
TWO MAJOR STRUCTURES OF THE CELL:
1. Cytoplasm
2. Nucleus
DNA is the principal molecular component of the
nucleus.
Most of the RNA is contained in a rounded structure, the
nucleolus.
Nucleolus
- Often attached to the nuclear membrane, a
double-walled structure that at some location is
connected to the endoplasmic reticulum.
Cytoplasm
- It makes up the bulk of the cell and contains
great quantities of all molecular components
except DNA. A number of intracellular
structures are found in the cytoplasm.
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Endoplasmic Reticulum
- A channel or a series of channels that allows the
nucleus to communicate with the cytoplasm
Mitochondria
- Powerhouse of the cell
- Large bean-shaped structure
- Macromolecules are digested in the
Mitochondria to produce energy for the cell
- Called the engine of the cell
Ribosome
- The small dot-liked structure
- It is the site of protein synthesis and therefore is
essential to normal cellular function.
- Ribosome are scattered throughout the
cytoplasm or the endoplasmic reticulum
Lysosomes
- The small pea-liked sacs
- It contains enzymes capable of digesting cellular
fragments and sometimes the cell itself
- It helps to control intracellular contaminants
10kGy t (1Mrad)- is the required dose to produce a
measurable change in any physical characteristic of the
molecule
The lethal dose in some single-cell organism, such as
bacteria, is measured in Gyt , but human cells can be
killed with a dose of less than 1 Gy t
NOTE: Nucleus is much more sensitive that the
cytoplasm to the effects of radiation
CELL FUNCTION
DNA
- Located in the nucleus
- Contains a molecular code that identifies which
proteins the cell will make. This code is
determined by the sequence of base pairs
(adenine-thymine and cytosine-guanine)
Codon
- A series of three base pairs
- Identifies one of the 22 human amino-acids
available for protein synthesis
Genetic message is transferred within the nucleus to a
molecule of mRNA. mRNA leaves the nucleus by way
of the endoplasmic reticulum and makes its way to a
ribosome, where is the genetic message is transferred to
yet another RNA molecule (tRNA)
tRNA searches the cytoplasm for the amino acids for
which it is coded. It attaches to the amino acid and
carries it to the ribosome, where it is joined with other During interphase, the chromosomes are not visible;
amino acids in sequence by peptide bonds to form the however, during mitosis, the DNA slowly takes the form
required protein molecule of the chromosomes as seen microscopically.

During prophase, the nucleus swells, and the DNA

becomes more prominent and begins to take structural
CELL PROLIFERATION form.
Cell Proliferation At metaphase, the chromosomes appear and are lined up
along the equator of the nucleus. It is during metaphase
- Is the act of a single cell or group of cell to
that mitosis can be stopped and chromosomes can be
reproduce and multiply in number
studied carefully under the microscope.
Two general types of cell
Anaphase is characterized by the splitting of each
1. Somatic Cell chromosome at the centromere, so that a centromere and
two chromatids are connected by a fiber to the poles of
2. Genetic Cell the nucleus. These poles are called spindles, and the
fibers are called spindle fibers. The number of
The genetic cell includes the oogonium of the female
chromatids per centromere has been reduced by half, and
and the spermatogonium of the male.
these newly formed chromosomes migrate slowly
All other cells in the body are somatic cells. toward the spindle.

When somatic cells proliferate or divide they undergo The final segment of mitosis, telophase, is characterized
mitosis. by the disappearance of structural chromosomes into a
mass of DNA and the closing off of the nuclear
Genetic cells undergo meiosis. membrane like a dumbbell into two nuclei. At the same
time, the cytoplasm is divided into two equal parts, each
Geneticists consider only two phases of the cell cycle,
of which accompanies one of the new nuclei.
mitosis (M) and interphase.
MEIOSIS
Mitosis, the division phase, is characterized by four sub
phases: prophase, metaphase, anaphase, and telophase Genetic material can be change during the division of
genetic cells, which is called meiosis. Genetic cells
Interphase
begin with the same number of chromosomes as somatic
- The portion of the cell cycle between mitotic cells-23 pairs (26 chromosomes).
events
Meiosis is the process whereby genetic cells undergo
- It is the period of growth of the cell between
reduction division
divisions
TISSUES AND ORGANS
MITOSIS
Tissues
Cell Biologists usually identify four phases of the cell
cycle: M,G1, S, G 2. These phases of the cell are - Collection of cells of similar structure and
characterized by the structure of the chromosomes, function
which contain genetic material DNA. The gap in cell
growth between M and S isG 1. G 1 is the pre-DNA Tissue Composition of the Body
Tissue Abundance
synthesis phase.
Muscle 43%
The DNA synthesis phase is S. During this period, each Fat 14%
Organs 12%
DNA molecule is replicated into two identical daughter
Skeleton 10%
DNA molecules. Blood 8%
Subcutaneous Tissue 6%
During S phase, the chromosome is transformed from a Bone Marrow 4%
structure with two chromatids attached to a centromere Skin 3%
to a structure with four chromatids attached to a Organs
centromere. The result is two pair of homologous
chromatids, that is, chromatids with precisely the same - Group of tissues
DNA content and structure.
Tissues and organs
The G 2phase is the post-DNA synthesis gap of cell
- Serve as discrete units with specific functional
growth. responsibilities.
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Organ system Connective and Supporting Tissue

- Tissues and organs combine into an overall
integrated organization
The principal organ systems of the body are the nervous
system, digestive system, endocrine system, respiratory
system, and reproductive system.
The cells of a tissue system are identified by their rate of
proliferation and their stage of development. Immature
cells are called undifferentiated cells, precursor cells, or
stem cells.
- They 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 cartilages are
examples of connective tissue
Muscle
- It is a special type of tissue that can contract.
- It is found throughout the body and is high in
protein content

Nervous Tissue
Response to Radiation is Related to Cell Type
Radio sensitivity Cell Type - It consists of specialized cells called neurons
High Lymphocytes that have long, thin extensions from the cell to
Spermatogonia distant parts of the body.
Erythroblasts - Nervous tissue is the avenue by which electrical
Intestinal crypt cells
impulses are transmitted throughout the body for
Intermediate Endothelial cells control and response
Osteoblast
Spermatids Two parts of organ: parenchymal and stromal part
Fibroblast
Parenchymal part contains tissues that represent that
Low Muscle Cells particular organ
Nerve Cells
The Stromal part is composed of connective tissue and
vasculature that provide structure to the organ.

Relative radio sensitivity of tissues and organs based on

clinical radiation oncology
PART II: FUNDAMENTAL PRINCIPLES OF
Level of Radio Tissue or Organ Effects
sensitivity RADIOBIOLOGY
High: 2-10 Gy t Lymphoid tissue Atrophy
(200-1000 rad) Bone Marrow Hypoplasia
Gonads Atrophy
LAW OF BERGONIE AND TRIBONDEAU
Intermediate Skin Erythma In 1906, two French scientist, Bergonie and Tribondeau,
10-50 Gyt Gastrointestinal Ulcer
theorized and observed that radio sensitivity was a
(1000-5000 rad) tract
Cornea Cataract function of the metabolic state of the tissue being
Growing Bone Growth arrest irradiated. This has come known as the Law of Bergonie
Kidney Nephrosclerosis and Tribondeau and has been verified many times.
Liver Ascites Basically, the law states that the radio sensitivity of
Thyroid Atrophy living tissue varies with maturation and metabolism.
Muscle Fibrosis LAW of BERGONIE and TRIBONDEAU
Low:>50 Gyt
Brain Necrosis o Stem cells are radiosensitive; mature
(>5000 rad) Spinal Transection
cells are radio resistant
o Younger tissues and organs are
radiosensitive
Epithelium
o Tissues with high metabolic activity are
- It is the covering tissue, and it lines all exposed radio sensitive
o A high proliferation rate for cells and a
surfaces of the body, both exterior and interior.
high growth rate for tissues result in
- It covers the skin, blood vessels, abdominal and increased radio sensitivity
chest cavities, and the gastrointestinal tract.

This law is principally interesting as a historical note in

the development of radiobiology. It has found some
application in radiation oncology. In diagnostic imaging,
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this law serves to remind us that foetuses are
considerably more sensitive to radiation exposure as are
children compared with the mature adults.
PHYSICAL FACTORS THAT AFFECT RADIO
SENSITIVITY
When one irradiates tissue, the response of the tissue is
determined principally by the amount of energy
deposited per unit mass--- the radiation dose in Gy t (rad).
Even under controlled experimental conditions,
however, when equal doses are delivered to equal
specimens, the response may not be the same because of
other modifying factors. A number of physical factors
affect the degree of radiation response.
LINEAR ENERGY TRANSFER
Linear energy transfer (LET) is a measure of the rate at
which energy is transferred from ionizing radiation to
soft tissue. It is another method of expressing radiation
quality and determining the value of the radiation
weighing factor (W R ¿used in radiation protection. LET
is expressed in units of kiloelectron volt of energy
transferred per micrometer of tract length in soft tissue
(keV/µm)
The LET of diagnostic x-rays is approximately
3keV/µm.
The ability of ionizing radiation to produce a biologic
response increases as the LET of radiation increases.
When LET is high, ionizations occur frequently,
increasing the probability of interaction with the target
molecule.
RELATIVE BIOLOGIC EFFECTIVENESS
As the LET of radiation increases, the ability to produce
biologic damage also increases. This effect is
quantitatively described by the relative biologic
effectiveness (RBE).Gy t
RELATIVE BIOLOGIC EFFECTIVENESS
RBE=
Dose of standard radiation necessary ¿ produce a given effect
The standard radiation, by convention, is orthovoltage x-
radiation in the range of 200 to 250kVp. This type of x-
ray beam was used for many years in radiation oncology
and in essentially all early radiobiologic research.
Diagnostic x-rays have an RBE of 1. Whereas radiation
with lower LET that diagnostic x-rays have an RBE less
than 1, radiations with higher LET have a higher RBE.
PROTRACTION AND FRACTIONATION
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If a dose of radiation is delivered over a long period of
time rather than quickly, the effect of dose is less. Stated
differently, if the time of irradiation is lengthened, a
higher dose is required to produce the same effect. This
lengthening of time can be accomplished in two ways.
If the dose is delivered continuously but at a lower dose
rate, it is said to be protracted. Six gray (600 rad)
delivered in 3- minutes at a dose of 2 Gy t /min is lethal
for a mouse. However, when 6Gyt is delivered at the
rate of 10mGy t / hr for a total time of 600 hours, the
mouse will survive.
Dose protraction and fractionation cause less effect
because time is allowed for intracellular repair and tissue
recovery.
If the 6-Gyt dose is delivered at the same dose rate, but in
12 equal fractions of 500mGy t ,all separated by 24
hours, the mouse will survive. In this situation, the dose
is said to be fractionated.
Radiation dose fractionation reduces effect because cells
undergo repair and recovery between doses. Dose
fractionation is used routinely in radiation oncology.
BIOLOGIC FACTORS THAT AFFECT RADIO
SENSITIVITY
In addition to these physical factors, a number of
biologic conditions alter the radiation response of tissue.
Some of these factors, such as age and metabolic rate,
have to do with the inherent state of tissue. Other factors
related to artificially introduced modifiers of the biologic
system
OXYGEN EFFECT
Tissue is more sensitive to radiation when irradiated in
the oxygenated, or aerobic, state than when irradiated
under anoxic (without oxygen) or hypoxic (low oxygen)
conditions. This characteristic of tissue radiation
response is called oxygen effect and is described
numerically by the Oxygen Enhancement Ratio (OER).
OXYGEN ENHANCEMENT
¿ RATIO
producethe sa me effect ¿
Dose of test radiation necessary ¿
OER=
Dose necessary under anoxic conditions ¿ produce a given effe
Generally, tissue irradiation is conducted under
conditions of full oxygenation. Hyperbaric (high
pressure) oxygen has been used in radiation oncology in
an attempt to enhance the radio sensitivity of nodular,
avascular tumors, which are less radio sensitive than
tumors with an adequate blood supply.
Diagnostic x-ray imaging is performed under conditions
of full oxygen
The OER is LET dependent. The OER is highest for
low-LET radiation, with maximum values of
approximately 3 that decreases to approximately 1 for
high-LET radiation.
AGE
The age of a biologic structure affects it radio sensitivity.
The response of humans is characteristics of this are-
related radio-sensitivity. Humans are most sensitive
before birth.
Afterbirth, sensitivity decreases until maturity, at which
time humans are most resistant to radiation effects. In
old age, humans again become somewhat more radio
sensitive.
RECOVERY
It vitro experiments shows that human cells can recover
from radiation damage. If the radiation dose is not
sufficient to kill the cell before its next division
(interphase death), then given sufficient time, the cell
will recover from the sublethal radiation damage it has
sustained.
Interphase death occurs when the cell dies before
replicating
This intracellular recovery is attributable to a repair
mechanism inherent in the biochemistry of the cell.
Some types of cell have greater capacity than others for
repair of sublethal damage. At the whole-body level, this
recovery from radiation damage is assisted through
repopulation by surviving cells.
If a tissue or organ receives a sufficient radiation dose, it
responds by shrinking. This is called atrophy, and it
occurs because some cells die and disintegrated and are
carried away as waste products.
If a sufficient number of cells sustain only sublethal
damage and survive, they may proliferate and repopulate
the irradiated tissue or organ.
NOTE: the combined processes of intracellular repair
and repopulation contribute to recovery from radiation
damage.
Simply:
Recovery=Intracellular repair+ Repopulation
CHEMICAL AGENTS
Some chemicals can modify the radiation response of
cells, tissues, and organs. For chemical agents to be
effective, they must be present at the time of irradiation.
Post-irradiation application does not usually alter the
degree of radiation response.
Radiosensitizers. Agents that enhance the effect of
radiation are called sensitizing agents. Examples include
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halogenated pyrimidines, methotrexate, actinomycin D,
hydroxyurea, and vitamin K.
The halogenated pyrimidines become incorporated into
the DNA of the cell and amplify the effects of radiation
on that molecule. All radiosensitizers have an
effectiveness ratio of approximately 2, that is, if 90%of a
cell culture is killed by 2Gyt (200 rad), then in the
presence of a sensitizing agent, only 1 Gy t (100 rad) is
required for the same percentage of lethality.
Radioprotectors. Radio protective compounds include
molecules that contain a sulfhydryl group (Sulfur and
hydrogen bound together), such as cysteine and
cysteamine. Hundreds of others have been tested and
found effective by a factor of approximately 2. For
example, if 6 Gy t (600 rad) is a lethal dose to a mouse,
then in the presence of a radioprotective agent, 12 Gyt
(1200 rad) would be required to produce lethality.
Radioprotective agents have not found human
application because, to be effective, they must be
administered at toxic levels. The protective agent can be
worse that the radiation.
HORMESIS
A separate and small body of radiobiologic evidence
suggest that a little bit of radiation is good for you. Some
studies have shown that animals given low radiation
doses live longer than controls. The prevailing
explanation is that a little radiation stimulates hormonal
and immune responses to other toxic environmental
agents.
Many non-radiation examples of hormesis can be found.
In large quantities, fluoride is deadly. In small quantities,
it is a known tooth preservative.
Regardless of radiation hormesis, we continue to
practice ALARA vigorously as a known safe approach
to radiation management.
RADIATION DOSE-RESPONSE RELATIONSHIPS
Although some scientists were working with animals to
observe the effects of radiation a few years after the
discovery of x-rays, these studies were not
experimentally sound, nor were their results applied.
With the advent of the age of the atomic bomb in the
1940’s, however, interest in radiobiology increased
enormously.
The object of nearly all radiobiologic research is the
establishment of radiation dose-response relationships. A
radiation dose-response relationship is a mathematical
relationship between various radiation dose levels and
magnitude of the observed response.
Radiation dose-response relationships have two
important applications in radiology. First, these
experimentally determined relationships are used to
designed therapeutic treatment routines for patients with
cancer.

Radiobiologic studies also have been designed to yield

information to the effects of low-dose radiation. These
studies and the dose-response relationships revealed
provide the basis of radiation management activities and
are particularly significant for diagnostic radiology.

Human responses to radiation exposure fall into two

types: early or late, high dose or low dose, deterministic
or stochastic.

Deterministic radiation responses usually follow high-

dose radiation exposure and an early response.
Radiation-induced skin burns represent a deterministic
response.

Stochastic responses are cancer, leukemia, or genetic

effects. Such responses usually follow low radiation
exposure and appear as a late radiation response.

Every radiation dose-response relationship has two

characteristics. It is either linear or non-linear, and it is
either threshold or non-threshold. These characteristics
can be described mathematically or graphically.

LINEAR DOSE-RESPONSE RELATIONSHIPS

- It is so named because the response is directly

proportionate to the radiation dose
- When the radiation dose is doubled, the response
to radiation likewise is doubled.
- Linear non-threshold types is when the dose-
response relationship intersect axis at zero or
below
- In a non-threshold dose-response relationship,
any dose, regardless of its size, is expected to
produce a response
- The Level Rn, called the natural response level,
indicates that even without radiation exposure
that type of response, such as cancer, occurs.
- Linear threshold are identified when they
intercept the dose axis at some value greater than
zero.

NON-LINEAR DOSE-RESPONSE RELATIONSHIPS

CONSTRUCTING A DOSE RESPONSE

RELATIONSHIP

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