Biological Effects

of Ionizing
Radiations

Biological Effects

X-radiation energy is transferred to the

irradiated tissues primarily by
Photoelectric and Comptons processes
which produce ionizations and excitations
of essential cell molecules such as DNA,
enzymes, ATP, coenzymes, etc.
The functions of these molecules are
altered.
The cells with damaged molecules can
not function normally.

Biological Effects

The severity of biological effect is

related to the type of molecule
absorbing radiation.
Effect on DNA molecule is more
harmful than on cytoplasmic
organelles

Mechanism of Action

Two mechanisms of radiation damage,

Direct action: Damage or mutation occurs at the
site where the radiation energy is deposited.
Indirect action: Energy is absorb from another
molecule. The radiation initially acts on water
molecules to cause ionization. The water is
abundantly present in the body (approx. 70 %
by weight)
Indirect effect accounts for 2/3rd of the damage,
direct effect is responsible for the remainder.

Indirect Action

The ions, H2O+ and H2O-, are very

unstable and break up into free radicals.

Free radicals:
highly reactive atoms and molecules
react with and alter essential molecules
that come in contact with them.
These altered molecules have different
chemical and biologic properties from the
original molecules. This translates to
biologic damage.

Indirect Action

Free radicals may also combine with

each other to produce hydrogen
peroxide
OH + OH-------> H2O2
Hydrogen peroxide is a cell poison
which may contribute to biological
damage

Radiation Effects at Cellular

Level

Point mutations: Effect of radiation

on individual genes is referred to as
point mutation.
The effect can be loss or mutation
in a gene or a set of genes.
The implication of such a change is
that the cell may now exhibit an
abnormal pattern of behavior.

Radiation Effects at Cellular

Level

Chromosome alterations: Several kinds

of alterations in the chromosomes have
been described. Most of these are
clearly visible under the microscope.
The effect upon chromosomes can
result in the breaking of one or more
chromosomes. The broken ends of the
chromosome seem to possess the
ability to join together again after
separation.

Chromosome Breaks

Chromosome Breaks

Such damage may be repaired

rapidly in an error-free fashion by
cellular repair processes
(restitution) using the intact second
strand as a template.
However, if the separation between
broken fragments is great, the
chromosome may lose part of its
structure (deletion).

Chromosome Breaks

If more than one break, the broken

fragments may join in different
combinations.
inversion of the middle segment
followed by recombination

Chromosome Breaks

Double-strand breakage: when

both strands of a DNA molecule are
damaged. Sections of one broken
chromosome may join sections of
another, broken chromosome.

Chromosome Breaks

A large proportion of damage will

result in misrepair which can result
in the formation of gene and
chromosomal mutations that may
cause malignant development.

Ionizing radiations also affect cell

division, resulting in arrested mitosis
and, consequently, in retardation of
growth.
The extent of arrested mitosis varies
with the phase of the mitotic cycle
that a cell is in at the time of
irradiation. Cells are most sensitive to
radiation during the last part of resting
phase and the early part of prophase.

Cytoplasmic Changes: Swelling of

mitochondria and changes in cell
wall permeability have been
observed.

Radiation Effects at Tissue

Level

Two types of biological effects may

appear in tissues after exposure to
ionizing radiation.
Somatic effects
Genetic effects

Radiation Effects at Tissue

Level

Somatic effects include responses

of all irradiated body cells except
the germ cells of the reproductive
system.
Somatic effects may be stochastic
or deterministic.

Radiation Effects at Tissue

Level

Genetic effects. Include responses

of irradiated reproductive cells.
Genetic effects become primarily
important when they are passed on
to future generations.

Somatic Effects

Basically, somatic effects are

classified in two categories:
Acute or immediate effects
Chronic or delayed(latent)
effects

Acute Somatic Effects

Appear rather soon after exposure

to a single massive dose of
radiation or after several smaller
doses of radiation delivered within
a relatively short period of time.
In general, effects which appear
within 60 days of exposure to
radiation are classified as acute
effects.

Delayed Somatic Effects

Delayed effects may occur anywhere

from two months to as late as 20
years or more after exposure to
radiation. The time lapse between the
exposure to radiation and the
appearance of effects is referred to as
the "latent period."
In radiobiology, the term latent
period is usually used only in relation
to stochastic effects (malignancy)

Variables in Somatic
Effects

The magnitude of somatic effects

depend on the following variables:
Individual
Species
Cellular and tissue
Extent of exposure (full or partial
body)
Total dose
Dose rate

Types of Biological
Responses
Chronic deterministic effects:
These effects are observed after large
absorbed doses of radiation. Doses
required to produce deterministic
effects are, in most cases, in excess of
1-2 Gy.
There is usually a threshold dose below
which the effects are not manifested.
With increasing dose the severity of
the effect increases.

Deterministic Effects

Skin. Excessive exposure of the skin to

ionizing radiation may result in erythema or
reddening of the skin, which is produced by
dilatation of small blood vessels beneath
the skin.
The dose of radiation required to produce
erythema of the skin is between 1.65-3.5
Gy.
Inflammation- 6-10 GY
Higher doses are associated with dermatitis.

Deterministic Effects

Hair. Epilation, or loss of hair, results

from exposure of the skin to 2.0-6.0
Gy. A latent period of about 3 weeks
ensues before the hair is lost.
The hair usually grows back in a few
weeks.
For permanent epilation, considerably
higher doses are required.

Deterministic Effects

Sterility.
Sterility results from destruction by
radiation of gonadal tissues which
produce mature sperm or ova.
A single dose of 4.0 Gy to the male
gonads is necessary to produce
permanent sterility.
The dose required to produce
permanent sterility in the female may
be 6.25 Gy or more.

Deterministic Effects

Cataract. Exposure of the lens of

the eye to radiation can cause
cataract (opacification of the lens).
The threshold for cataract induction
is 2.0-5.0 Gy for a single exposure
and approximately 10.0 Gy or more
for exposures protracted over a
period of months or years.

Therapeutic Radiation to Oral

Tissues

Standard therapeutic radiation dose

for treating cancer is approximately
50 to 60 Gy.
Administered over a period of 10 to
14 weeks at the rate of
approximately 2.5 Gy twice weekly.

Radiation Effect on Oral Tissues :

Developing teeth

<10 Gy has very little or no visible

effect.
Effects to an infant may include:
destruction of tooth bud, tooth
malformation and delay in
eruption.

Radiation Effect on Oral Tissues :

Bone
The most serious complication: jaw
osteoradionecrosis.
This is primarily due to damage to the
blood vessels of the jaw and
consequent decreased capacity of the
bone to resist infection.
Tooth extraction or other injury:
possibility of bone infection and
necrosis becomes very high.
More common in the mandible than in
maxilla.

Radiation Effect on Oral Tissues :

Salivary glands

Xerostomia: marked and progressive

loss of salivary secretion.
The mouth becomes dry (xerostomia)
and tender.
The pH of saliva falls below normal (5.5
as compared to 6.5 in normal saliva).
Whether xerostomia is temporary or
permanent depends upon the volume of
glands exposed.

Radiation Effect on Oral Tissues :

Mucosa

Mucositis. At 3rd or 4th week, oral mucosa

becomes red and inflamed (mucositis). As
the therapy continues, mucosa forms yellow
pseudomembrane.
Mucositis is most severe at the end of the
treatment period.
Healing begins soon after treatment and is
usually complete in about two months after
therapy. The mucosa tends to become
atrophic, thin and relatively avascular
permanently. Dentures may frequently cause
oral ulceration.

Radiation Effect on Oral Tissues:

Taste buds

Taste acuity is reduced or lost in about 4

weeks into the radiation treatment.
In general, bitter and acid flavors are
more severely affected when posterior
third of the tongue is irradiated and salt
and sweet when anterior third is
irradiated.
Complete recovery of taste usually occurs
in two to four months following treatment
completion.

Deterministic Effects

Embryological and developmental

effects. therapeutic doses of
radiation delivered to the pelvic
region of a pregnant woman can
result in the death of the fetus or in
the birth of an abnormal child.
The developmental effects on the
embryo are strongly related to the
stage at which the exposure occurs .

Embryological and
The first 2 weeks of pregnancy: most
developmental

critical period. If the dose is high, the

fetus will die. The congenital
anomalies are rare at this stage.
The highest incidence of
malformations is the period of
organogenesis (3-8 weeks of
pregnancy).
The threshold doses are relatively low:
100-200 mGy for most malformations
and 200 mGy for brain damage.

Whole body effects of

radiation

Acute Radiation
Syndrome

Radiation Sickness.
Symptom complex that occurs after
the exposure of the entire body, or a
major portion of the body to a large
dose of radiation (above 1.0 Sv)
within a short period of time. The
effect may vary from a transient
illness to death..

Acute Radiation
Syndrome

Acute Radiation
Syndrome

Prodromal Syndrome. 1.0 - 2.0 Gy

exposure.
Individual usually develops G.I.
symptoms such as nausea,
vomiting, weakness, fatigue, and
anorexia. These symptoms usually
disappear soon.

Acute Radiation
Syndrome

Hematopoietic Syndrome. 2.0 - 7.0 Gy.

Severe injury to hematopoietic system
of the bone marrow, irreversible
damage to the proliferative capacity of
the of the spleen and bone marrow.
Rapid fall in the number of circulating
granulocytes, platelets and erythrocytes
Rampant infection, due in part from
lymphopenia, granulopenia, and
anemia. The death occurs in 10 to 30
days.

Acute Radiation
Syndrome

Gastrointestinal syndrome. 7.0 to 15.0

Gy.
Extensive damage to GI system:
anorexia, nausea, vomiting, severe
diarrhea and malaise in a few hours after
exposure. Basal epithelial cells of the
intestinal villi are destroyed.
Loss of plasma and electrolytes into the
intestines, hemorrhages and ulcerations.
Results in dehydration and loss of
weight.

Acute Radiation
Syndrome

Cardiovascular and CNS syndrome.

Excess of 50 Gy.
Death occurs within 1 or 2 days.
Common symptoms are:
uncoordination, disorientation and
convulsions. This is due to damage
to the neurons and brain
vasculature.

Stochastic Effects

The most important effect of ionizing

radiation on human mortality is judged
to be neoplasia and leukemia .
Radiation in this regard is considered a
two-edged sword. It cures cancer and it
also causes cancer.
The probability of carcinogenic effect
increases with dose.
It is currently judged that there is NO
THRESHOLD below which the effect will
not occur. Severity of the effect is
independent of the radiation dose.

Stochastic EffectsGeneralizations

Cancers other than leukemia typically

start to appear 10 years following
exposure (5 years for leukemia) and
the increased risk remains for the
lifetime of the exposed individuals.
The risk from exposure during fetal
life, childhood and adolescence is
estimated to be about 2-3 times as
large as the risk during adulthood.

Stochastic Effects

Leukemia: The incidence of leukemia

(other than chronic lymphocytic) rises
following exposure of red marrow.
Wave of leukemia appear within 5
years of exposure, and return to base
line rates within 40 years.
Children under 20 are more at risk
than adults.

Stochastic Effects

Thyroid cancer: The incidence of

thyroid carcinoma increases
following radiation exposure.
The susceptibility is greater early in
childhood that later in life.
Females are 3 times more
susceptible than males to both
radiation induced and spontaneous
thyroid cancer.

Stochastic Effects

Bone cancer: Patients treated for

childhood cancer demonstrate an
increasing risk of bone sarcomas.
Brain and nervous system cancer:
Ionizing radiation exposure can induce
tumors of the CNS. Most tumors are
benign such as neurilemommas and
meningiomas (average mid-brain dose
of 1 Gy). Malignant brain tumors have
also been demonstrated, but only at
radiation therapy doses.

Stochastic Effects

Esophageal cancer: The data

regarding esophageal cancer is
sparse. Excess cancers are found in
the Japanese A-bomb survivors as
well as in patients treated with Xrays for ankylosing spondylitis.

Stochastic Effects

Salivary-gland cancer: An increased

incidence of salivary gland tumors
has been demonstrated in patients
therapeutically irradiated for the
diseases of head and neck, in the
Japanese A-bomb survivors and in
persons exposed to diagnostic
levels of x-radiation (cumulative
parotid dose of 0.5 Gy or more).

Stochastic Effects

Skin: Association between ionizing

radiation exposure and development of
basal cell carcinoma is well documented
in the literature. There is minimal
indication of association with malignant
melanoma.
Other organs: Excess cases of multiple
myeloma as well as malignancy of
paranasal sinuses have also been
demonstrated in patients receiving
radiation doses.