Radiobiolog

Prepared by : Aldrin Lopez, RRT ,MSRT

 To recap and to solve problem about
basic of radiological units and its uses

To identify the deterministic effect of

radiation in human

Objectiv
To understand the Law of bergonie &
es tribondeau

To explore Radbiology related to

Radiologic technology
Reference
s
• X – radiation
• Are type of electromagnetic radiation
EMR refers to radiation that has both
electrical and magnetic properties.
• Dual nature of x-ray energy
• Act both waves and like particle.
• Affected by their wavelength
• Classification of Radiation
i. Alpha Radiation
ii. Beta Radiation
iii. Electromagnetic waves such
gamma rays. as
 Alpha Radiation
• Alpha radiation is a heavy, very short-range particle and is actually an ejected helium nucleus. Some characteristics
of alpha radiation are:

i. Most alpha radiation is not able to penetrate human skin.

ii. Alpha-emitting materials can be harmful to humans if the materials are inhaled, swallowed, or absorbed
through open wounds.
iii. A variety of instruments has been designed to measure alpha radiation. Special training in the use of
these instruments is essential for making accurate measurements.
iv. A thin-window Geiger-Mueller (GM) probe can detect the presence of alpha radiation.
v. Some Instruments cannot detect alpha radiation because alpha radiation is not penetrating.
vi. Alpha radiation travels only a short distance (a few inches) in air but is not an external hazard.
vii. Alpha radiation is not able to penetrate clothing.

“Examples of some alpha emitters: radium, radon, uranium, thorium.”

 Beta Radiation
• Beta radiation is a light, short-range particle and is an ejected electron. Some characteristics of beta radiation
are:

i. Beta radiation may travel several feet in air and is moderately penetrating.
ii. Beta radiation can penetrate human skin to the "germinal layer," where new skin cells are
produced. If high levels of beta-emitting contaminants are allowed to remain on the skin for a
prolonged period, they may cause skin injury.
iii. Beta-emitting contaminants may be harmful if deposited internally.
iv. Most beta emitters can be detected with a survey instrument and a thin-window GM probe (e.g.,
"pancake" type).
v. Clothing provides some protection against beta radiation.

“Examples of some pure beta emitters: strontium-90, carbon-14, tritium, and sulfur-35.”
Gamma and X Radiation
• Gamma radiation and x rays are highly penetrating electromagnetic radiation. Some characteristics of these
radiations are:

i. Gamma radiation or x rays can travel many feet in air and many inches in human tissue.
ii. X rays are like gamma rays. X rays, too, are penetrating radiation. Sealed radioactive sources and
machines that emit gamma radiation and x rays respectively constitute mainly an external hazard to
humans.
iii. Gamma radiation and x rays are electromagnetic radiation like visible light, radio waves, and
ultraviolet light. These electromagnetic radiations differ only in the amount of energy they have.
iv. Dense materials are needed for shielding from gamma radiation. Clothing provides little shielding
from penetrating radiation but will prevent contamination of the skin by gamma-emitting radioactive
materials.
Gamma
v. radiation is easily detected by survey meters with a sodium iodide detector probe.
• “Examples of some gamma emitters: iodine-131, cesium-137, cobalt-60, radium-226, and technetium-99m.”
Source
of
human
to
radiation
Radiation quantities and units
Radiologic • Roentgen/Exposure
• Rad/Dose

Units • The unit of radiation absorbed

dose

Roentgen, • The unit of radiation exposure or

intensity • The quantity of radiation
received by the patient

Rad, Rem, • It is defined as a unit of radiation

quantity (1928)
& Curie • Applies only to x-rays & gamma
rays & their interaction with air
• Symbol: R
• SI Unit: air kerma (Gya)
• 1 R: 2.58 x 10-4 C/kg (official)
• It is used for any type of ionizing
radiation & exposed matter, not
just air
• Symbol: rad
• SI Unit: gray (Gyt)
• Special Unit: J/kg
• 1 Rad: 100 erg/g or 10-2 Gyt
• Erg (J): a unit of energy
Radiologic • Rem/Equivalent Dose • Curie (Ci/Bq)

Units • The unit of occupational radiation

exposure
• A unit of radioactivity
Roentgen, • It is used to expressed the
quantity of radiation received by
• The unit of quantity of
radioactive material
Rad, Rem, radiation workers & populations
• Symbol: rem
• Symbol: Ci

& Curie • SI Unit: Sievert (Sv)

• Special Unit: J/kg
• Application: occupational
radiation monitors
• SI Unit: Becquerel (Bq)
• Special Unit: s-1
• 1 Ci: 3.7 x 1010 nuclei
disintegration per second
(Bq)
• Exposure
• exposure can be thought of like the concentration of x-ray energy per
unit area and it is measured in units of Roentgen or the SI units C/kg
• Increasing mAs increasing exposure
• Absorbed Dose
• Absorbed dose is a measure of the energy deposited per unit mass of
tissue.
• The traditional unit for measuring the absorbed dose is the rad. In this
table we have the conversion between rads and Gy(mGy).
• Equivalent Dose
• The damage caused by radiation to individuals depends on type of
radiation that is incident on the body and the anatomy that is
irradiated.
• Effective Dose
• Not all organs are equally radiosensitive and a means is needed to
account for this varied radio sensitivity across organ and tissue types.
Measure Units Formula

Exposure -- Coulumb/Kilogram

Air Kerma Gy Gy = 1Joule /kilogram

Absorbed dose (D) Gy D = 1 joule /kilogram

Equivalent dose Sv EqD = D x WR

Effective Dose Sv EfD = D x WR x WT

• The coulombs of electric charge produced per kilogram of air
in a measure of

• A. effective Dose
• B. absorbed Dose
• C. exposure
• D. equivalent Dose
• A radiation measurement describing the energy of ionization in air is
termed

• A. entrance skin Dose

• B. absorbed Dose
• C. exposure
• D. Air Kerma
• A radiographic exposure result in 0.015 joules of energy absorbed by
the liver. If the liver weighs 0.9 kilograms , what is the total
absorbed dose to the liver ?

• A. 0.0167 Gy
• B. 0.0135 Gy
• C. 60 Gy
• D. 0.07 C
• A radiation worker received gonadal dose of 25mGy over the
course of a year . If 100% of this dose was from x-ray , what is the
equivalent dose?

• A. 25 mGy
• B. 25 mSv
• C. 3 mSv
• D. 3 mGy
• The thyroid of radiation worker is exposed to an absorbed dose of 10
mGy from Alpha – emitting radionuclides . Calculate the effective
Dose

• A. 7 mGy
• B. 8 mSv
• C. 0.4 mSv
• D. 10 mGy
• During AP scoliosis x-ray , the breast , gonads and stomach of patient
received a dose of 3 mGy. What is the total effective dose ?

• A. 0.32 mSv
• B. 0.0035 mSv
• C. 0.96 mSv
• D. I don’t care
• An accident in a nuclear medicine facilities result in a whole body
absorbed dose of 56 mGy. What is the effective dose ?

• A. 56 mSv
• B. 102 mSv
• C. 32 mSv
• D. 56 mGy
• Types of effects
• If the radiation response increases in severity with increasing radiation dose, it is
called Deterministic effect
• occurs within days after the radiation exposure.

• if the incidence of the radiation response increases with increasing radiation dose, it is
called a stochastic effect
• not observed for months or years.
 Huma Populations Whom Radiation Effects Hav
n In Been Observed e

Population Effect
American radiologists Leukemia, reduced life span
Atomic bomb survivors Malignant disease
Radiation accident victims (e.g., Chernobyl) Acute lethality

Marshall Islanders Thyroid cancer

Uranium miners Lung cancer
Radium watch-dial painters Bone cancer
Patients treated with 131I Thyroid cancer
Children treated for enlarged thymus Thyroid cancer

Children of Belarus (downwind from Chernobyl) Thyroid cancer

Huma Populations Whom Radiation Effects Hav
n in Been Observed e

Population Effect

Patients with ankylosing spondylitis Leukemia

Patients who underwent Thorotrast studies Liver cancer

Irradiation in utero Childhood malignancy

Volunteer convicts Fertility impairment

Cyclotron workers Cataracts
• The effects of fetal irradiation include all of the following except?

• a. Childhood malignancy
• b. Congenital malformation
• c. Diminished growth and development
• d. Erythema
• e. Neonatal death
• Which of the following human responses to ionizing radiation would
be categorized as a late effect?

• a. Central nervous system syndrome

• b. Gastrointestinal syndrome
• c. Eye damage
• d. Extremity damage
• e. Hematologic depression
Radiation
biology
Covalent & ionic
Bond
•A covalent bond is a chemical bond that involves the
sharing of electron pairs between atoms.

• Ionic bonding is a type of chemical bonding that

involves the electrostatic attraction between
oppositely charged ions
 •“Covalent bonds are more common than ionic bonds in the
molecules of living organisms. For instance, covalent
bonds
are key to the structure of carbon-based organic molecules
like our DNA and proteins.”
• At nearly every stage in the
sequence, it is possible to
repair radiation damage and
recover.

• Radiobiology is the study of

the effects of ionizing
radiation on biologic tissue.
 • 1. Acute radiation syndrome
• a. Hematologic syndrome
• b. Gastrointestinal syndrome

DETERMINIS • c. Central nervous system syndrome

TIC EFFECTS • 2. Local tissue damage

• a. Skin
OF RADIATION • b. Gonads

ON HUMANS
• c. Extremities

• 3. Hematologic depression
• 4. Cytogenetic damage
STOCHASTIC • 1. Leukemia
• 2. Other malignant disease
• 4. Shortening of life span

EFFECTS OF • a. Bone cancer • 5. Genetic damage

RADIATION • b. Lung cancer
• c. Thyroid cancer
• a. Cytogenetic damage
• b. Doubling dose
ON • d. Breast cancer • c. Genetically significant
HUMANS dose
• 3. Local tissue damage
• a. Skin
• b. Gonads
• c. Eyes
 • 1. Prenatal death
• 2. Neonatal death
EFFECTS OF
• 3. Congenital malformation
FETAL • 4. Childhood malignancy
IRRADIATI • 5. Diminished growth and development
ON
• Early Effect of Radiation
• Radiation response occurs within minutes
or days after radiation exposure

• Late Effect of Radiation

• Radiation response that is not observe for
6 months or longer after radiation
exposure
Atomic
composition of the
body
• 85% of the body consists of hydrogen and
oxygen.

• Atomic Composition
• It determines the character & degree of
the radiation interaction that occurs
WATER
• The simplest & the most abundant molecular constituent in the body
• Important Role: delivering energy to the target molecules (contribute to radiation effects)
approximately 80% of human substance.
• Composition: two atoms of Hydrogen & 1 atom of Oxygen
• Functions:
• Provide some form & shape
• Assist in maintaining body temperature
• Enter into some biochemical reactions
 • Molecular & Tissue Composition
• It defines the nature of radiation response
• Macromolecules: proteins, lipids (fats), carbohydrates
(sugars & starches) & nucleic acids are
macromolecules
• Principal Organic Molecules: proteins, lipids
CELL &
carbohydrates
THEORY
• Macromolecules are very large molecules
sometimes consistthat
of hundreds of thousands
of
atoms.
• Proteins, lipids, and carbohydrates are the principal classes of organic molecules.

• Organic Molecule
• Life-supporting & contains carbon

• Nucleic Acid
• The rarest molecule in the body
• Concentrated in the nucleus of a cell (DNA)
• The most critical & radiosensitive target molecule
• Water and carbon dioxide are end products in the
catabolism

• Catabolism breaking down into smaller pieces of

macromolecules

• Anabolism, the production of large molecules

from small,
• Metabolism
• Catabolism & anabolism

• Proteins
• Long chain macromolecules that consist of a linear sequence of amino acids connected by peptide bonds
• Protein Synthesis: used 22 amino acids
• Approximately : 15 % of molecular composition of the body
• Functions:
• Provide structure & support (muscles)
• Enzymes, hormones & antibodies

• Protein Synthesis
• The metabolic production of proteins
 Linear • Protein = AA—AA—AA—AA …
Sequence/ • where AA is the amino acid, and — is the peptide
Arrangement: bond.
• The generalized formula for a protein is CnHnOnNnTn
• , where the subscript “n” refers to the number of atoms of each element in the molecule.

• In general, 50% of the mass of a protein molecule is

• carbon, 20%
• oxygen, 17%
• nitrogen, hydrogen 7%
• 6% other elements.
• Enzymes
• 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
• Molecules that exercise regulatory control over some body functions
• They are produced & secreted by endocrine glands
• Endocrine Glands: pituitary, adrenal, thyroid, parathyroid, pancreas & gonads
• Antibodies
• A primary defense mechanism of the body against infection & disease

• Antigen
• Invasive & infectious agent
• Lipids
• Organic macromolecules composed solely of carbon, hydrogen, & oxygen
• General Formula: CnHnOn
• Structural Configuration: represented by oleic acid molecules
• Two Types of Molecules:
• Glycerol – 1 molecule
• Fatty acid – 3 molecules
• Functions:
• Thermal insulator from environment
• Fuel for the body by providing energy stores
Lipids
structures
• Carbohydrates
• Similar to lipids but their structure is different
• First considered to be watered or hydrated carbons
• It is also called saccharides
• Sugars: monosaccharides & disaccharides and polysaccharides
• Chief Function:
• To provide fuel for cell metabolism
• Function:
• Provide shape & stability
• Carbohydrates also are called saccharides.

• Carbohydrates are classified according to size

• Monosaccharide's,
• Disaccharides,
• Polysaccharides

• Monosaccharides and disaccharides are sugars.

• Polysaccharides are largest among the three and include plant starches and animal glycogen.
• Monosaccharide’s
• Mono ( one ) saccharides ( sugar )
• Single chain or single ring structure
• Contain 3- 7 carbon atoms

• The most important monosaccharide's in the body

• Glucose ,
• Fructose
• Galactose
• Ribose
• deoxyribose
• Disaccharides/ double sugar
• Form when two simple sugars are joined by a synthesis reaction called dehydration
synthesis

• Important disaccharides
• Sucrose ( glucose – fructose ) sugar cane
• Lactose ( glocuse – galactose ) found in milk
• Maltose ( glucose – glucose ) malt sugar
• Polysaccharides
• Long branching chain of link/ “ many sugar “
• Starch and glycogen is major importance to the body
• Glucose
• A simple sugar
• The ultimate molecule that fuels the body
• Chemical Formula: C6H12O6

• Glycogen
• A human polysaccharide
• It stored in tissues of the body
• It used only when quantities of the simple sugar (glucose) are inadequate
• Nucleic Acids
• A very large and extremely complex macromolecules
• Two Principal Nucleic Acids: DNA & RNA
• Function: growth & development of the cell (protein synthesis)
 • Deoxyribonucleic Acid (DNA)
• The control center for life
• It contains all the hereditary information that
represents a cell or whole individual (germ cell)
• Location: nucleus

DN • Function: it serves as the command or control

molecule for cell function

A • Sugar Component: deoxyribose

• Base Component: thymine
• Configuration: double-helix
• The radiation sensitive target molecules
 • Nitrogenous Organic Bases

Nitrogenous • Attached to each deoxyribose molecule

• Purines: adenine & guanine
Organic • Pyrimidine's: thymine & cytosine

Bases • Sequence of Base Bonding in DNA:

• Adenines bonded to thymines
• Cytosines bonded to guanines
DN
A
• Nucleotide
• The base sugar-phosphate combination
• strung together in one long-chain macromolecule.

• Ribonucleic Acid (RNA)

• Principal Location: cytoplasm
• Two Types: messenger RNA & transfer RNA
• Sugar Component: ribose rather than deoxyribose
• Base Component: uracil
• Configuration: single-helix
 • 1. Ribosomal – It has a specific role to play in carrying
out DNA’s instruction for building proteins

RNA has three • 2. messenger – carries the information for building the
protein from the DNA gens to the ribosomes, the
major protein –synthesizing sites

varieties • 3. transfer – ferries amino acids to the ribosomes.

Translation of the message and the binding together
of amino acids to form the protein .
• Which of the following is an example of a macromolecule?

• a. A free radical
b. A lipid
c. An amino acid
d. Salt
e. Water
• The breaking down of macromolecules into water and carbon dioxide
is:

• a. Anabolism.
• b. Catabolism.
• c. Homeostasis.
• d. Hormesis.
• e. Metabolism.
• Which of the following molecules is a protein?

• a. A lipid
• b. A nucleic acid
• c. A salt
• d. An amino acid
• e. An enzyme
• Which of the following base pairs is allowed for DNA?

• a. Adenine-cytosine
• b. Adenine-guanine
• c. Cytosine-thymine
• d. Guanine-cytosine
• e. Thymine-guanine
• Which of the following is the nitrogenous organic base found in RNA
but not in DNA?

• a. Adenine
• b. Cytosine
• c. Guanine
• d. Thymine
• e. Uracil
• The nucleic acids of the cell:

• a. Are found only in the nucleus.

• b. Are macromolecules.
• c. Consist of DNA and RNA.
• d. Have a backbone of peptide bonds.
• e. Store energy.
 The
plasma
membrane / cell
•membrane
flexible plasma membrane
defines the extent of a cell,
thereby separating two of the
body’s major fluid
compartments.
Cytoplasmi
c
Organelles
• organelles (“little organs”)
specialized cellular
compartments or structures,
each performing its own job to
maintain the life of the cell.

• Some organelles, the no

membranous lack
organelles,
membranes.
• Cytoplasmic Organelles
• organelles (“little organs”) specialized
cellular compartments or structures,
each performing its own job to maintain
the life of the cell.
• Mitochondria They are the power
plants of a cell, providing most of its ATP
supply.
• Ribosomes are small, dark-staining
granules composed of proteins and a
variety of RNAs called ribosomal RNAs.
Cell • Mitosis / somatic cell
division
• Four phases

Division • Mitosis is the series of

• interphase –
resting stage or
events that parcels out the phase
replicated DNA of the • prophase –
mother cell to two daughter
preliminary
cells.
stage or phase
•• metaphase
anaphase – – stage
stageofof
equatorial grouping
separation
• telophase – completion
of division
Prophas Prophase –
preliminary stage preparation of cells
4. Centrosomes divided into
two centrosomes one which
for the next stage migrates to each pole of the
e cell body
1. 46 chromosomes become
condense, rodlike and visible to light
5. A spindle of fiber forms
between the newly formed
2. Duplication chromosome become centrosomes
doubled and form 46 pairs of
chromatids, each one
chromatids identical to 6. Nuclear membrane
each
mate , each gene duplicated
disappear

3. Paired chromatids separate except

at one point near the centromere 7. Nucleolus also disappear
 • Metaphase –
• equatorial grouping
• Chromatids line-up the equator
Metaphas • Paired chromatids become arranged at the equator of
the spindle , one pair attached to a fibers of the

e spindle
 • Anaphase
• Paired chromatid separates from each other
• One chromatid of each pair migrates along its fiber to
Anaphas a centrosome at each pole
• Forty six chromatid become chromosomes of fine

e filament grouped at the centrosomes

 • Telophas
e • completion of cell division
• 46 chromosomes a threadlike filament forms new
nucleous
• Spindle and aster disappear

Telophase • Nuclear membrance form around 46 chromosomes at

each end dividing cells
• Nucleolus form
• each daughter cell is duplication of the parent cell
with 46 chromosomes
Four phases of cell
cycle
• M, G1, S & G2

• G1 Phase
• Pre-DNA synthesis phase
• The gap in cell growth between M & S
• S Phase
• The DNA-synthesis phase
• DNA: replicated into two identical daughter DNA
molecules
• Chromosome: replicate form a two-chromatid
structure to a four-chromatid structure
• G2 Phase
• The post-DNA synthesis gap of the cell growth
Meiosi • Meiosis / genetic cell division
• The process whereby
• Cell maturation –
In order to preserve the
s genetic
undergo reduction
cells normal number of
chromosomes
division
• Second Division: not
accompanied by S This processed is called “
phase oogenisis “
• Result: no
replication
• Ova 46 During division chromosome
chromosomes & reduced to 23 ( haploid or
spermatozoa 46 miosis )
chromosomes
• Number of
chromosomes
reduce to one half
• 23 chromosome one will have “x” and “y”
• Along with the 22 other single
chromosomes
• 23 chromosomes will donated by
each parent cells
• Female “x+x “ male is x+y
 Gene
• Geness–
 - to be the fraction of DNA molecule
considered of
 chromosomes
-Each genes said to produce single enzymes
that responsible for single chemical reaction
 -determined the traits of hereditary factors of the offspring
 -genes are contained in a single DNA
 TISSUE AND ORGANS
TISSUE COMPOSITION OF
THE BODY
TISSUE ABUNDANCE
Muscle 43%
Fat 14 %
Organs 12 %
Blood 8%
Subcutaneous tissue 6%
Bone marrow 4%
Skin 3%
RESPONSE TO RADIATION IS RELATED TO CELL
TYPE
Radiosensitivity Cell Type
High sensitivity Lymphocytes
Spermatogonia
Erythroblasts
Intestinal crypt cells

Intermediate Endothelial cells

Osteoblasts
Spermatids
Fibroblasts

Low Muscle cells

Nerve cells
• Epithelium
• The covering tissue
• It lines all the exposed surfaces of the body, both exterior & interior
• It covers the skin, the blood vessels, the abdominal, chest cavities & GI tract

• Connective & Supporting Tissue

• It binds tissue & organs together
• Composition:
• High in protein
• Fibers
• Characteristic: highly elastic
• Examples: bone ligaments & cartilage
• Muscle Tissue
• A special type of tissue that can contract
• Composition: high in protein content

• Nervous Tissue
• The avenue by which electrical impulses
are transmitted throughout the body for
control & response
• Composed of specialized cells neurons
• Radiosensitivity of Tissues & Organs
• Determined by the function of the
organ in the body
• The rate at which cells mature within
the organ
• The inherent radiosensitivity of the
cell type
• Principal Aim of the Study of Radiobiology
• To understand radiation dose-response relationships

• Dose-Response Relationship
• A mathematical & graphic function that relates radiation dose to observed response

• Jean Bergonie & Louis Tribondeau (1906)

• Theorized & observed that radiosensitivity was a function of metabolic state of tissue being
irradiated
 • 1. Stem cells are radiosensitive; Mature cells are
radioresistant

• 2. Younger tissues and organs are radiosensitive

LAW OF
BERGONIE & • 3. Tissues with high metabolic activity are
radiosensitive

• 4. A high proliferation rate for cells & a high

TRIBONDE growth rate for tissues result in increased

radiosensitivity

AU
• Approximately what percentage of the body is water?

a. 20
b. 35
c. 50
d. 65
e. 80
• RNA:

• a. Contains all the hereditary information representing a cell.

• b. Is a principal component of a hormone.
• c. Is located principally in the cytoplasm of the cell.
• d. Is located principally in the nucleus of the cell.
• e. Serves as the command or control molecule for all function.
• During which of the following subphases of meiosis do the
chromosomes appear and line up along the equator of the nucleus?

• a. Anaphase
• b. Metaphase
• c. Prophase
• d. Telophase
• e. None of the above
• The body is organized in such a way that:

• a. Differentiated cells are immature.

• b. Epithelial cells are usually found inside organs.
• c. Mature cells are called stem cells.
• d. Organs combine to form tissues.
• e. Tissues and organs form an organ system.
• Which of the following are parts of the law of Kergonie and
Tribondeau?

• a. A fetus is less radiosensitive than an adult.

• b. Stem cells are radiosensitive.
• c. The more mature a cell, the more radiosensitive it is.
• d. When metabolism is high, radiosensitivity is low.
• e. When proliferation rate is high, so is radioresistance.
• The law of Bergonie and Tribondeau states that:

• a. Mature cells are more sensitive than stem cells.

• b. Metabolic activity results in radioprotection.
• c. Radiosensitivity increases with increasing hypoxia.
• d. Radiosensitivity increases with proliferation rate.
• e. The older a cell, the more radiosensitive it is.
• LET is measured in which of the following?

• a. Gray
• b. keV/rad
• c. keV/um
• d. rad
• e. rad/um
• Physical Factors That Affect Radiosensitivity

• Linear Energy Transfer (LET), Relative Biologic Effectiveness (RBE), Protraction & Fractionation
• Linear Energy Transfer (LET)
• A measure of the rate at which energy is transferred from ionizing radiation to soft tissue
• Another Method of:
• Expressing radiation quality
• Determining the value of the radiation weighting factor (WR)
• Used in radiation protection
• Expressed in: keV/μm
• Diagnostic X-rays: 3 keV/μm
• As LET Increases:
• Increases the ability to produce biologic damage
• Increases the probability of interaction with the target molecule
• Radiation Weighting Factor (WR)
• Factor used in radiation protection that accounts for differences in biologic effectiveness
between different radiations
• Former Name: quality factor

• Relative Biologic Effectiveness (RBE)

• Ratio of the dose of standard radiation necessary to produce a given effect to the dose of
test radiation needed for the same effect

• The RBE-LET relationships are correlated with local energy deposition in

small
regions of the cells.
• Orthovoltage X-rays
• The standard radiation by convention
• Range: 200-250 kVp
• It was used in radiation oncology and early radiobiologic research.

• Diagnostic x-rays have an RBE of 1.

• Whereas radiations with lower LET than diagnostic x-rays have an RBE less than 1, radiations
with higher LET have a higher RBE.
 LET & RBE OF VARIOUS RADIATION
DOSES LET
TYPE OF RADIATION RBE
(keV/μm)
25 MV x-rays 0.2 0.8
60Co gamma rays 0.3 0.9
1 MeV electrons 0.3 0.9
Diagnostic x-rays 3.0 1.0
10 MeV protons 4.0 5.0
Fast neutrons 50.0 10
5 MeV alpha particles 100.0 20
Heavy nuclei 1000.0 30
• As linear energy transfer (LET) increases, relative biologic effectiveness (RBE)
also increases, but a maximum value is reached followed by a lower RBE
because of overkill.
• Protraction
• The dose is delivered continuously but at a lower dose rate

• Fractionation
• The dose is delivered at the same dose in equal portions at regular intervals
• It reduces the effect
• Rationale: cells undergo repair & recovery between doses

• Dose protraction & fractionations cause less effect because time is allowed for intracellular
repair & tissue recovery!
• Biologic Factors That Affect Radiosensitivity

• Oxygen Effect,
• Age,
• Recovery,
• Chemical Agents
• Hormesis
 • Oxygen Effect
• Oxygenated/Aerobic State: tissue is more sensitive to
radiation than anoxic & hypoxic

• Oxygen Enhancement Ratio (OER)

• Ratio of the dose necessary to produce a given effect
Biologic under anoxic conditions to the dose necessary to
produce the same effect under aerobic conditions
Factors That • enhancement of therapeutic or detrimental effect of
Affect ionizing radiation due to the presence of oxygen.
Radiosensitiv • LET dependent

ity • Low LET: higher OER

 • Hyperbaric/High Pressure Oxygen
• It has been used in radiation oncology
Biologic • Purpose: to enhance the radiosensitivity of
nodular & avascular tumors
Factors That
Affect • Diagnostic x-ray imaging is performed under
Radiosensitiv conditions of full oxygenation.
ity
Biologic Factors That Affect
Radiosensitivity
• Age
• Before Birth: most radiosensitive
• After Birth: radiosensitivity decreases
• Maturiry: most radioresistant
• Old Age: somewhat more radiosensitive
• Chemical Agents
• Radiosensitizers: agents that enhance the effect of radiation
• Radiosensitizers are drugs or chemical compounds that enhance the lethal effects
of
radiation.
• Examples:
• Halogenated pyrimidines
• Methotrexate
• Actinomycin D
• Hydroxyurea
• Vitamin K
• Ex :
• The halogenated pyrimidines become incorporated into the DNA of
the cell and amplify the effects of radiation on that molecule.
• Radioprotectors: agents that reduces the effect of radiation
• compounds used to prevent/protect the non-tumor cells from the
harmful effects of radiation
• Not found human application
• Rationale: it must be administered at toxic levels
• Examples:
• Cysteine
• Cysteamine
• Hormesis
• A little bit of radiation is good for us
• Rationale: it stimulates hormonal & immune responses
to other toxic environmental agents
 • Radiation Dose-Response Relationship
• A mathematical relationship between various
radiation dose levels & magnitude if the observed
response
RADIATION DOSE-
RESPONSE • Two Important Applications in Radiology
• It is used to design therapeutic treatment routines
RELATIONSHIPS for patient with cancer
• It revealed provide the basis for radiation control
activities
• Human responses to radiation exposure fall
into two types:

• early or late, high dose or low dose, and

deterministic or stochastic.
 • Two Types of Radiation Responses
• Deterministic/Nonstochastic
Two Types of • It follows a high-dose exposure

Radiation • Early radiation response

• Example: skin burn
Responses • Stochastic
• It follows a low-dose exposure
• Late radiation response
• Examples: cancer, leukemia & genetic effects
• Every radiation dose-response relationship has two
characteristics. It is either linear or nonlinear, and it is
either threshold or nonthreshold.
 • Linear or Nonlinear
• Threshold or Nonthreshold

Two • Threshold Dose

Characteristic of • The level below which there is no response

Dose-Response
• Linear Dose-Response Relationship
Relationship • The response is directly proportionate to the dose
• Linear Nonthreshold Type: intersects at zero or below
• Linear Threshold Type: intercept the dose axis at some
value greater than zero
• “ Radiation-induced cancer, leukemia, & genetic effects
follow a linear-nonthreshold dose-response
relationship! “
Linear dose-response relationships A and B are nonthreshold
types; C and D are threshold types. RN is the normal incidence
or response with no radiation exposure.
• directly proportional to radiation dose . When
the radiation dose is doubled, the response to
radiation likewise is doubled.

• At zero dose, relationship A exhibits a measurable

response, RN. The level RN, called the natural response
level, indicates that even without radiation exposure, that
type of response, such as cancer, occurs.
 • Nonlinear Dose-Response Relationship
• It is used in establishing radiation protection
Nonlinear guidelines for diagnostic imaging
Dose- • The response is not directly proportional to
the dose
Response • Nonlinear Nonthreshold: large response
Relationsh results from a very small radiation dose
ip • Nonlinear Threshold Type: below the
threshold, no response is measured
• S-Type/Sigmoid-Type
• Example: skin effects resulting from high
dose fluoroscopy

• “ Diagnostic radiology is concerned almost

exclusively with the late effects of radiation
exposure & therefore, with linear,
nonthreshold dose-response relationships! “
• The inflection point occurs when the curve stops bending up and begins bending down. Above this
level, incremental doses become less effective. Relationship C is sometimes called an S-type, or
sigmoid type, radiation dose-response relationship.
 • “ A dose-response relation is produced when
high-dose experimental data are
extrapolated to low doses! “

• Extrapolation
CONSTRUCT
• Estimation of value beyond the range of
ING A DOSE- known values
RESPONSE • predict by projecting past experience or
RELATIONSHIP known data
• Results in: linear, nonthreshold dose-
response relationship
• Radiation Interaction With Water
• The principal radiation interaction in the body

• In Vitro
• Irradiation outside of the cell or body
• considerable radiation dose required to produce a measurable
is
effect.

• In Vivo
• Irradiation with the cell or body
• demonstrates that macromolecules considerably more radiosensitive
in are
their natural state.
 Molecula
r • Three Major Effects When Macromolecules Are
Radiobiolo Irradiation in a Solution In Vitro

gy • Main-chain Scission, Cross-linking & Point Lesion

RADIATION OF

MACROMOLEC
ULES
 • Main-Chain Scission
• The breakage of the backbone of the long-chain
macromolecules
• Result:

Main- • Reduction of a long, single molecule into many

smaller molecules
Chain • Effects:
• Reduces the size of the macromolecules
Scission • Reduces the viscosity of the solution
• Very thick & slow to flow
• Measurement of Viscosity: determines the degree
of main-chain scission
 Cross-
Linking
• Cross-Linking
• Process side spurs created by
irradiation
of & to a
neighboring macromolecules
attached or to
another segment of the same
molecule

• Effect: increases the viscosity of

the macromolecular solution
 Point
Lesion
• Point Lesion
• Any change that results in
the impairment or loss of
function at the point of a
single chemical bond
• Not detectable
• Radiation Effects on DNA
• Chromosome aberration or cytogenetic damage
• Abnormal metabolic activity
• Structural change

• Type of Chromosome Aberrations

• Terminal deletion
• Dicentric formation
• Ring formation
 DAMAGE • Unobservable Radiation Response of DNA
• Main-chain scission with only one side rail severed
THAT • Result: structural change
CA • Main-chain scission with both side rail severed
INTHEN • Result: structural change
• Main-chain scission & subsequent cross-linking
DNA
OCCU • Result: structural change
MOLECUL R
E
 • Rung breakage causing separation of bases
damage • Result: structural change

can
thatoccur • Change in or loss of a base
• A molecular lesion of DNA
in • Destroys the triplet code
• May not be reversible
the DNA

molecul
e
Radiolysis of
Water
• Radiolysis of Water
• Because human body is an
the aqueous solution that
approximately
water
contains 80%
molecule.
• decomposition of water molecules due to ionizing
radiation
• Dissociation of water into other molecular products
as a result of irradiation
• Initial Result
• Ion Pair:
• First, the ion pair may rejoin into a
stable water molecule. In this case, no
damage occurs.
• Second, if these ions do not rejoin, it is
possible for the negative ion(the electron) to
attach another molecule
water
to
• HOH+& e-
• The radiolysis of water results in
the formation of ions and free
radicals.
 Hydrogen Peroxide

Poisonous to the cell & therefore acts as a

Hydroge toxic agent

n Chemical Formula: H2O2

Peroxide
Formed By:
• HO* + HO* or
• HO* +
HO*
2
2
DIRECT &
INDIRECT EFFECTS

• Direct Effect
• If the initial ionizing event occurs on the target
molecule

• Indirect Effect
• If the initial ionizing event occurs on a distant,
noncritical molecule
• The energy is transferred to the target
molecule

• “The principal effect of radiation on humans is

indirect!
 • Target Theory
• For a cell to die after radiation exposure, its
target molecule must be inactivated
• It was used to represent cell lethality
• It can be used to describe non lethal radiation-
Target induced cell abnormalities
Theor • sensitive key molecule serves as
the basis for target theory.
y the

• “DNA is the target molecule!

• According to target theory,
cell death will occur only if
the target molecule is
inactivated. DNA, the target
molecule, is located within
the cell nucleus.
• Target
• An area on the cell occupied by the target molecule or by a sensitive site on the
target molecule
• The interaction between radiation and cellular components
is random; therefore, when an interaction
does occur with a target, it
occurs randomly.

• Hit
• Radiation interaction with the target or molecules
• It occurs through both direct & indirect effect
• It isn’t simply an ionizing event, but rather an ionization that inactivates the target
molecule
 • Direct & Indirect Effects
• Low-LET Radiation & Absence of Oxygen:
• Low probability of hit on the target molecules
• Rationale: relatively large distances
between ionizing event
Direct &
Indirect Effects • Low-LET Radiation & Presence of Oxygen:
• High probability of hit on the target molecules
• Rationale:
• Formation of free radical
• Enlarged volume of effectiveness
surrounding each ionization
 • High-LET Radiation & Absence of Oxygen:
• High probability of a hit by direct effect
• Rationale: close distance between

Direct & ionization event

Indirect Effects • High-LET Radiation & Presence of Oxygen:

• Does not result in additional hits
• Rationale: the maximum number of hits
has already been produced by direct effect
with high-LET radiation
 • If normal cells are planted
individually in a Petri
dish and are incubated
for 10 to 14 days
, they divide many times and
produce a visible colony
consists of many cells. This
that

CELL SURVIVAL cell cloning. is

KINETICS • Cell Cloning

• Process by which normal cells produce a visible
colony in a short time

• The lethal effects of radiation are determined by

observing cell survival, not cell death!
Two Models of
Cell
Survival

• Two Models of Cell Survival

• Single-Target, Single-Hit Model
• Multi-Target, Single-Hit Model
 Single-Target, Single-Hit Model

Single-Target, It applies to biologic targets such

Single-Hit as enzymes, viruses & bacteria

Model
Equation:

• S = N/No = e-D/D37
• It represents a threshold
D37
• When the radiation dose reaches a level sufficient to kill 63% of the cells (37% survival)
• A measure of the radiosensitivity of the cell
• Low D37: highly radiosensitive
• High D37: highly radioresistant
• If there were no wasted hits (uniform
interaction), is the dose that
D37
would be sufficient to kill 100% of the
cells!
Multi-Target, Single-Hit
Model
• It applies to more complicated biologic system such
as human cells
• Equation:
• S = N/N0 = 1 – (1 - eD/D0)n
• It represents a threshold
 • Cell Survival
• Very Low Radiation Dose: nearly 100%
• High Radiation Dose: fewer cells survive
Cell • Rationale: more sustain a hit in both target
molecules
Survival • Survived Cells: have one target hit
• Dose-Response Relationship: appear as single-
target, single-hit model
• D0
• The mean lethal dose
• A constant related to the radiosensitivity of
the cell
• It is equal to D37 in the linear portion of the
graph
• Large D0: radioresistant cells
• Small D0: radiosensitive cells
• DQ
• The threshold dose
• A measure of the width of the shoulder of
the multitarget single-hit model
• It is related to the capacity of the cell to
recover from sublethal damage
• Large DQ: the cell can recover readily from
sublethal radiation damage
 • A damage that must be accumulated before the cell
dies
• Wider Shoulder:
• More sublethal damage that can be sustain
• The higher the value of DQ

Sublethal
Damage • Split-Dose Irradiation
• Designed to describe the capacity of a cell to
recover from sublethal damage
Deterministic effect of
Radiation
• Early Effects of Radiation
• A radiation response in human within a few days to months
• It is described as deterministic

• Deterministic Radiation Response

• Biologic response whose severity varies with radiation dose
• A dose threshold usually exists
 • Death
ACUTE • The most devastating human response to
radiation exposure
RADIATI
ON • Acute Radiation-Induced Lethality
LETHALITY • It is of only academic interest in diagnostic
radiology
 PRINCIPAL EARLY EFFECTS OF RADIATION EXPOSURE ON HUMANS & THE
APPROXIMATE THRESHOLD DOSE
Effect Anatomic Site Threshold Dose
Death Whole body 200 rad/2 Gyt
Hematologic
depression Whole body 25 rad/250 mGyt
Skin erythema Small field 200 rad/2 Gyt
Epilation Small field 300 rad/3 Gyt
Chromosome Whole body 5 rad/50 mGyt
aberration
Gonadal dysfunction Local tissue 10 rad/100 mGyt
• Acute Radiation Syndrome
• Radiation sickness that occurs in human after the whole-body dose s of 1 Gy (100 rad) or
more of ionizing radiation delivered over a short time

• Three Syndromes
• Hematologic Death, Gastrointestinal (GI) Death & Central Nervous System (CNS) Death
Prodomal
Period

Prodomal Period
• The immediate response of radiation sickness
• Approximate Dose: > 100 rad
• Mean Survival Time:
• Clinical S&S: nausea, vomiting & diarrhea
 Latent Period
• The time after exposure during which there is no
sign of radiation sickness
Latent • extends from hours or less (at doses in excess of 50
Gyt) to weeks (at doses from 1 to 5 Gyt).
Period • Approximate Dose: 100-10, 000 rad
• Mean Survival Time:
• Clinical S&S: none
 • Manifest Illness
• The dose necessary to produce a given
syndrome and the mean survival time are the
principal quantitative measures of human
Manifest radiation lethality
• At very high radiation doses, the latent period
Illness disappears altogether. At very low radiation
doses, there may be no prodromal period at
all.
 • It is characterized by a reduction in white cells, red
cells & platelets
• appear in a matter of a few hours and may persist for
several days.
• Approximate Dose: 2 to 10 Gyt (200–1000 rad)
• Mean Survival Time: 10-60 days
Hematolog • Clinical S&S: nausea, vomiting, diarrhea, anemia,
leukopenia, hemorrhage, fever & infection
ic • Prodomal Period: mild symptoms (matter of a few
Syndrome hours)
• Latent Period: general feeling of wellness
• Period of Manifest Illness: vomiting, mild diarrhea,
malaise, lethargy & fever
• Recovery: 2-4 weeks or 6 months (full)
• Cause of Death: generalized infection, electrolyte
imbalance & dehydration
 • Gastrointestinal Syndrome
• It occurs principally because of severe damage to the
cells lining the intestines
Gastrointestinal • Approximate Dose: 10 to 50 Gyt (1000–5000 rad)

Syndrome • Mean Survival Time: 4-10 days

• Clinical S&S: same as hematologic plus electrolyte
imbalance, lethargy, fatigue & shock
• Prodomal Period: vomiting & diarrhea occur within hours of exposure or
w/n a
day
• Latent Period: 3 to 5 days follows (no symptoms present)
• Period of Manifest Illness: second wave of nausea & vomiting, followed by
diarrhea, anorexia
• Cause of Death: unprevented rapid progression of symptoms (4 to 10 days of
exposure)
 • Central Nervous System Syndrome
• Its ultimate cause is elevated fluid content of the
Central brain
• Characterized By: increased intracranial
Nervous pressure, vasculitis & meningitis
• Approximate Dose: > 50 Gyt (5000 rad) (death
System within a matter of hours to days)
Syndrom • Mean Survival Time: 0-3 days
• Initial onset : extremely nervous and confused,
e burning sensation in the skin, lose vision, lose
consciousness within the first hour
• Clinical S&S: same as GI plus ataxia, edema,
system vasculitis & meningitis
• Prodomal Period: severe nausea & vomiting
• Latent Period: earlier symptoms disappear
• Period of Manifest Illness: more severe
prodomal symptoms, disoriented, loss
muscle coordination, dyspnea, convulsive
seizures, loss of equilibrium, ataxia &
lethargy
• Outcome : always death within a few days of
exposure
 •
LD50/60
• The dose of radiation to the whole body that
causes 50% of irradiated subjects to die within
60 days
LD50/60 • It quantitatively measured the acute radiation
lethality
• Humans: 350 rad
 Mean Survival Time
• Average time between exposure & death
• As the whole-body radiation dose increases, the average
time between exposure and death decreases.
Mean Survival • As the radiation dose increases from 2 to 10 Gyt (200–
1000 rad), the mean survival time decreases from
Time approximately 60 to 4 days;
• Hematologic Syndrome: dose dependent
• GI Syndrome: remain constant
• CNS Syndrome: dose dependent
• Local Tissue Damage
• It follows a threshold-type dose response relationship
• Characteristic: deterministic response

• Local Tissues That Can Be Affected Immediately

• Skin
• Gonads
• Bone marrow
Partial-Body Irradiation
• A higher dose is required to produce a
response
• It affects organ & tissue
• Effect: cell death
• Result: shrinkage of the organ or tissue

• Atrophy
• The shrinkage of an organ or tissue due to
cell death
 • Skin
• The tissue with which we have had the most experience
• Three Layers
• Epidermis: outer layer
• Basal Cells: its lowest layer
• Dermis: intermediate layer of connective tissue
EFFECT ON SKIN • Subcutaneous: layer of fat & connective tissue
• Other Accessory Structures: hair follicles, sweat glands &
sensory receptors
• Cells Replacement Rate: 2 %/day (50 % for GI)
• Skin Effects: nonlinear, threshold dose-response relationship
• Basal Cells
• The stem cells that mature as they migrate to the surface of the epidermis

• Damage to basal cells results in the earliest manifestation of radiation injury to the
skin!

• In earlier times, the tolerance of the patient’s skin determined the limitations of
radiation oncology with orthovoltage x-rays (200–300 kVp x-rays).
• Erythema
• 1st wave
• A sunburn-like reddening of the skin
• The first observed biologic response to radiation exposure
• dose of 3 to 10 Gyt (300–1000 rad) first or second day

• Moist Desquamation
• 2nd wave
• The clinical tolerance for radiation therapy

• Desquamation
• outer layer of the skin starts to replace itself.
• 3rd wave
• Ulceration & denudation of the skin
• required interruption of treatment.
X-ray-Induced Erythema
• One of the hazards to the patient the early of radiology

• Skin-Erythema Dose (SED)

• Dose of radiation, usually about 200 rad, that causes redness of the skin

• Epilation/Alopecia/Fox Mange
• Loss of hair

• SED50
• The dose required to affect 50% of those irradiated
• Dose: 500 rad
 POTENTIAL RADIATION RESPONSES OF SKIN FROM HIGH-DOSE
FLUOROSCOPY

Potential Radiation Approximate Time of

Threshold Dose Onset
Response

Early transient erythema 200 rad/ 2Gy Hours

Main erythema 600 rad/ 6Gy 10 days

Temporary epilation 300 rad/ 3Gy 3 weeks

Permanent epilation 700 rad/ 7Gy 3 weeks

Moist desquamation 1500 rad/ 15Gy 4 weeks

 • Testes
• The male gonads
• It produces spermatogonia & matures into sperm

EFFECTS ON GONADS • Ovaries

• The female gonads
• It produces oogonia & matures into ovum
• Germ Cells
• Produced by both ovaries & testes

• Gametogenesis
• The process of development of germ cells
 • Progression of Germ Cell
• Male: Spermatogonia (most radiosensitive) →
Progression of → Spermatid → Sperm
Spermatocyte

Germ Cell
• Female: Primordial Follicle → Mature Follicle
m
( ost radiosensitive) → Corpus Letuem
→  Ovum
• Oogonia
• The stem cells of the ovaries
• They multiply in number only before birth & during fetal life

• Primordial Follicles
• They grow to encapsulate the oogonia
• Oocyte
• A matured oogonia

• Ovum
• A mature female germ cell
• Fertilization: 400-500 ova
• Number of years of menstruation times 13 per year
• Spermatogonia
• The stem cells of the testes
• Continually being produced from stem cells progressively
through a number of stage to maturity

• Spermatocyte
• A matured spermatogonia

• Spermatid
• A matured spermatocyte

• Spermatozoa/Sperm
• A mature male germ cell
• Maturation Process: 3-5 weeks
• Ovaries
• Irradiation Causes
• Early Life: atrophy
• After Puberty: suppression & delay of menstruation
• 10 rad: suppresses menstruation
• 25-50 rad: increased genetic mutations
• 200 rad: temporary sterility
• 500 rad: sterility
• They decline in radiosensitivity, reaching a minimum in the
age range of 20 to 30 years, and then increase continually
with age.

• 100 mGyt (10 rad)

• suppress menstruation in a mature female.

• 2 Gyt (200 rad)

• produces temporary infertility

• 5 Gyt (500 rad)

• results in permanent sterility.
• Testes
• Irradiation Causes: atrophy
• 10 rad/ 100mGy: reduce the number of spermatozoa
• 200 rad: temporary sterility (approximately 2 months
after irradiation and persists for up to 12 months.)
• 500 rad: sterility (male patient normally retains his
ability to engage in sexual intercourse)
• Spermatogonial Stem Cells
• The most sensitive phase in the gametogenesis of the spermatozoa

• Male Gametogenesis
• A self-renewing system
HEMATOLOGIC
EFFECTS
• Periodic Blood Examination
• The only monitoring performed on x-ray & radium
workers before,
• Before the introduction of personnel radiation
monitors
• Total cell counts & a white cell differential count

• Under no circumstances is a periodic blood examination

recommended as a feature of any current radiation
protection program!
• Hematologic Depression

• Threshold Dose: 25 rad

• Hemopoietic System

• Another example of cell renewal system

• Same with gametogenesis

• Bone marrow

• Circulating blood

• Lymphoid tissue
• Lymph nodes, Spleen & Thymus

• Principal Effect of Radiation:

• Depressed number of blood cells in the peripheral circulation
• Pluripotential Stem Cell
• Stem cell that has the ability to develop into several different types of mature cells
• It produces lymphocytes, granulocytes, thrombocytes & erythrocyte

• Lymphocytes/White Blood Cells

• Blood cells involved in the immune response
• Manufactured by spleen & thymus
• Lifetime in the Bone Marrow: varying (hours or years)
• Lifetime in the Peripheral Blood: varying (hours or years)
• Granulocytes
• Scavenger type of cells used to fight bacteria
• Lifetime in the Bone Marrow: 8-10 days
• Lifetime in the Peripheral Blood: couple of days
• Recovery: 2 months

• Thrombocytes/Platelets
• Blood cells involved in the clotting of blood to prevent hemorrhage
• Lifetime in the Bone Marrow: 5 days
• Lifetime in the Peripheral Blood: 1 week
• Recovery: 2 months
• Erythrocytes/Red Blood Cells
• Blood cells that are transportation agents for oxygen
• Less sensitive than the other blood cells
• Rationale: long lifetime in the peripheral blood
• Lifetime in the Bone Marrow: 8-10 days
• Lifetime in the Peripheral Blood: 4 months
• Recovery: 6 months to 1 year
• Bone Marrow
• It manufactures most circulating blood cells including lymphocytes
• Child: uniformly distributed throughout the skeleton
• Adult: restricted to flat bones such as ribs, sternum, skull & ends of long
bones
• HEMOPOIETIC CELL SURVIVAL
• PRINCIPAL RADIATION RESPONSE OF HEMOPOIETIC SYSTEM
• Decrease in the number of all types of blood cells in the circulating peripheral blood

• LETHAL INJURY
• It causes depletion of mature circulating cells

• LYMPHOPENIA
• 1st cell to become affected after exposure to radiation
• Result : Reduced in number of lymphocytes
• GRANULOCYTOSIS
• Rapid rise in number of granulocytes
• followed first by a rapid decrease and then a slower decrease in number
(granulocytopenia).
• 15 to 20 days after irradiation.
• Minimum granulocyte levels are reached approximately 30 days after
irradiation
• Recovery: take 2 months
• THROMBOCYTOPENIA
• Depletion of platelets
• reach a minimum in about 30 days and recover in approximately 2 months, similar to
the response of granulocytes.
• ERYTHROCYTES
• less sensitive than the other blood cells
• Reason : very long lifetime in the peripheral blood
• Injury: not apparent for a matter of weeks
• Recovery : take 6 months to a year.
• CYTOGENETIC EFFECTS
• Developed in the early 1950s
• Study about human genetic analysis and radiation genetics.
• The technique calls for a culture of human cells to be prepared and treated so that
the chromosomes of each cell can be easily observed and studied.
• Studies involving high-dose fluoroscopy have shown radiation-induced
chromosome aberrations soon after the examination was performed.

• Without question, high doses of radiation cause chromosome

aberrations. Low doses no doubt also do so, but it is technically
difficult to observe aberrations at doses that are less than
approximately 100 mGyt (10 rad).
• Normal Karyotype
• CHROMOSOMES STRUCTURAL RADIATION
DAMAGE
• When radiation interacts with chromosomes,
the interaction can occur through direct or
indirect effect. In either mode, these
interactions result in a hit.
• RECIPROCAL TRANSLOCATION
• It requires a karyotype for detection
• result : no loss of genetic material, simply a
rearrangement of the genes.
• all or nearly all genetic codes are available; they
simply may be organized in an incorrect
sequence.

• POINT GENETIC MUTATIONS

• Undetectable even with karyotype construction
• Hit
• Radiation interaction with chromosomes

• DNA Hit
• It results in an invisible disruption of
the molecular structure of the DNA
• CHROMOSOME HIT
• It produces a visible derangement of
the chromosome
• It represents severe damage to the DNA
SINGE-HIT CHROMOSOME ABERRATION
• Visualized & recorded during the M phase
• Irradiation During G1 Phase
• Cause: chromatid break
• During S Phase: replicated
• During Metaphase: a chromosome with material
missing from the ends of two sister chromatids &
two acentric fragments
•Irradiation During G2 Phase
• Causes: single or double chromatid break
• During S Phase: replicated
• During Metaphase: a chromosome with
an arm that is obviously missing
genetic material & a chromatid
fragment
• CHROMATID DELETION
• The breakage of a chromatid

• ISOCHROMATID
• Fragments in chromosome aberrations

• ACENTRIC
• Without a centromere
• MULTI-HIT CHROMOSOME ABERRATION
• Not uncommon
• Irradiation During G1 Phase
• Causes: ring & dicentric chromosomes
• Ring: when two hits occur on the
same chromosome
• Dicentric: when adjacent chromosome each
suffer one hit & recombine
• Irradiation During G2 Phase: similar to
G1 phase but rarer
• Similar aberrations can be produced in the G2 phase
of the cell cycle; however, such aberrations again
require.

• 1) either the same chromosome be hit two or more

times or
• (2) adjacent chromosomes be hit and
joined together. However, these events are rare.
• STICKINESS
• A condition in which the mechanism for the joining
of chromatids depends

• RADIATION-INDUCED RECIPROCAL TRANSLOCATION

• Multi-hit chromosome that require karyotype analysis
for detection
• Results in:
• No loss of genetic material
• Simply a rearrangement of the genes
• KINETICS OF CHROMOSOME ABERRATION
• Single-Hit Aberration:
• It occurs at very low doses of radiation
• Dose-Response Relationship: linear, nonthreshold
• Multi-Hit Aberration:
• It occurs when the radiation dose
exceeds approximately 1 Gyt (100 rad),
• Dose-Response Relationship:
nonlinear, nonthreshold
• The general dose-response relationship for
production of single- and multi-hit aberrations is
shown in Figure 33-13.

• Single-hit aberrations are produced with a linear,

nonthreshold dose-response relationship.
• Multi-hit aberrations are produced following a
nonlinear, nonthreshold relationship. A number
of investigators have experimentally
characterized these relationships
• MULTI-HIT ABERRATIONS
• considered to be the most significant in terms
of latent human damage

• APPROXIMATE CHROMOSOME ABERRATION

FREQUENCY
• Two single-hit aberrations per rad per 1000 cells
• One multi-hit aberration per 10 rad per 1000
cells
• THE HUMAN GENOME
• After approximately 10 years of scientific
investigation, in the year 2000, the human genome was
mapped. This was a worldwide project involving many
different laboratories.
Humans have about 35,000 genes distributed along the
DNA of the 46 chromosomes.

• Many human health effects have now been

associated with aberrations identified for specific
genes and
researchers are finding ways to correct these genetic
defects or replace them. A wonderful example is brca1 and
Stochastic
Effects of
Radiation
• Late Effects of Radiation

• The result of low doses delivered over a long period

• It is also known as stochastic effects
• Stochastic effects of radiation exposure exhibit an increasing incidence of response—not
severity—with increasing dose
• No dose threshold has been established for a stochastic response.
• Followed linear dose-response relationship
• Principal Late Effects: radiation-induced malignancy & genetic effects
• Others: shortening of life span & local tissue effect
• Stochastic Radiation Response

• Probability of frequency of the biologic response to

radiation as a function of radiation dose
• No threshold dose
• Radiation Exposure Experience By Personnel

• Low dose & low LET

• Chronic in nature
• Delivered intermittently over long periods
• Epidemiologic Studies
• Studies of large numbers of people exposed to a toxic substance
require considerable statistical analyses. It is difficult
• Rationale:
• The dose usually is not known but presumed to be low
• The frequency of response is very low
• Result: do not convey the statistical accuracy associated with
observations of early radiation effects
 • Radiodermatitis
• Developed on early radiologists who performed
LOCAL fluoroscopic examination
• Skin Appearance: callused, discolored & weathered
TISSUE (hands & forearms)

EFFECTS • Skin Characteristics: very tight, brittle & severely

crack
or flake
 • Irradiation of Blood-Forming Organs
• Early Response: hematologic depression
• Late Response: leukemia

• Irradiation of Circulating Lymphocytes

Chromosome • Early & Late Response: chromosome damage

s • For example, individuals irradiated accidentally with rather

high radiation doses continue to show chromosome
abnormalities in their peripheral lymphocytes for as long as
20 years
• Radiation-Induced Cataract
• It occurs on the posterior pole of the lens
• Dose-Response Relationship: nonlinear, threshold
• Radiosensitivity of Lens: age-dependent
• Increased Age:
• Greater radiation effect
• Shorter latent period
• 5-30 years
• Average: 15 years
• High-LET Radiation
• Examples: neutron & proton radiation
• It has a high RBE for the production of cataracts
• Lens of the Eye
• Threshold Dose
• Cataracts: > 1000 rad (10 Gyt)
• Acute X-ray Exposure: 200 rad (2 Gyt)
• Fractionated Exposure: > 1000 rad (10 Gyt)
• Occupational Exposure: impossible to reach
• Dose in CT Scan: 5 rad per slice
• Protective lens shields are not normally required
• Rationale: no more than one or two slices intersect the lens

• It is nearly impossible for a medical radiation worker to reach the threshold dose.

• The dose-response relationship for radiationinduced cataracts is nonlinear,

threshold.
LIFE SPAN • At worst, humans can expect a reduced life span of
SHORTENI approximately 10 days for every rad!

NG
 • Stochastic Effect
• It has no dose threshold
• All radiation-induced malignancies

RADIATION- • Radiation-Induced Leukemia

INDUCED • Dose-Response Relationship: linear, nonthreshold

MALIGNANCY • Latent Period: 4-7 years

• At-Risk Period: 20 years
• Breast Cancer
• Watch dial painter
• Ingestion of radium
• Radium:
• It behaves similar to calcium & deposit in bone
• Half Life: 1620 years
• Relative Risk: 122:1
• Absolute Risk: 1 x 10-4 rem-1

• Tritium (3H) & Promethium (147Pm)

• Currently used in watch dial painting
• Skin Cancer
• Begins: development of radiodermatitis
• Patient treated with orthovoltage (200-300 kVp) or
superficial x-ray (50-150 kVp)
• Dose-Response Relationship: threshold
• Latent Period: 5-10 years
• Breast Cancer
• Risks:
• Patient treated with non-image-intensified fluoroscopy
for TB
• Patient treated with x-rays for acute postpartum mastitis
• Absolute Risk: 6 cases/106 persons/rad/year
• Lung Cancer
• Caused: dusty mine environment
• Risks:
• Workers in the Bohemian pitchblende mines
• Uranium Miners
• Half Life: 109 years
• Relative Risk: 8:1
• Smoking Uranium Miners
• Relative Risk: 20:1
 • Before Pregnancy
• Concern: interrupted fertility

RADIATION & • During Pregnancy

• Concern: possible congenital effects in newborn

PREGNANCY • Postpregnancy
• Concern: suspected genetic effects
• Irradiation in Utero
• It is time related & dose related
• Concerns Two Types of Exposures:
• That of the radiation worker
• That of the patient
• Effects:
• Prenatal death
• Neonatal death
• Congenital malformation
• Malignancy induction
• General impairment of growth
• Genetic effects
• Mental retardation
• Response: all-or-none variety
• Radiation-induced abortion occurs or pregnancy is carried to term without no ill effect
• Major Organogenesis
• From 2nd-10th week
• Two Effects May Occur:
• Skeletal & organ abnormalities
• Congenital abnormalities
• Severe: neonatal death

• The relative risk of childhood leukemia after irradiation in

utero is 1.5!
RELATIVE RISK OF CHILDHOOD LEUKEMIA AFTER IRRADIATION IN UTERO BY TRIMESTER

Time of X-ray Examination Relative Risk

First trimester 8.3

Second trimester 1.5

Third trimester 1.4

Total 1.5
 • Effects After 10 Rad in Utero
• Spontaneous Abortion
• Least concern
• Rationale: all-or-none effect
Effects After 10 • Time of Exposure: 0-2 weeks
Rad in Utero • Natural Occurrence: 25%
• Radiation Response: 0.1%
• Congenital abnormalities
• Time of Exposure: 2-10 weeks
• Natural Occurrence: 5%
• Radiation Response: 1%
• Mental Retardation • Impaired growth & development
• Time of Exposure: 2-15 weeks • Time of Exposure: 0-9 months
• Natural Occurrence: 6% • Natural Occurrence: 1%
• Radiation Response: 0.5% • Radiation Response: nil

• Malignant Disease • Genetic mutation

• Time of Exposure: 0-9 months • Time of Exposure: 0-9 months
• Natural Occurrence: 8/10,000 • Natural Occurrence: 10%
• Radiation Response: 12/10,000 • Radiation Response: nil