Unit 1.

Biological Effects
of Ionizing Radiations
 Dominion Dental Journal, 1897
Excerpts: Danger in X-rays
So as to better diagnose the dental
troubles of which Miss Josie McDonald of
New York complained, Drs. Nelson T.
Shields and George F. Jernignan a month
ago decided to have an X-ray photograph
taken of the young womans face.
The picture was taken by Mr. J. OConnor,
and as a result of the exposure to the
strong mysterious light, Ms. McDonald is
now suffering from burns.
 A few days after being
photographed. The skin on the young
womans face, neck, shoulder, left
arm and breast became blistered and
finally peeled off.
One ear swelled to three times its
natural size and it is said there has
been no hearing in it since.
The first picture taken of the young
woman, OConnor admits, was
unsatisfactory, and a second and
successful attempt was made. The first
exposure lasted eight minutes and the
last one thirteen minutes. Besides the
burns, large patches of Miss McDonalds
hair have fallen out
 Biological Effects
First case of radiation-induced
human injury was reported in the
literature in 1896.
Who discovered X rays and when?
First case of X-ray induced cancer
was reported in 1902
 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, mostly on
DNA:
Direct action: Damage or mutation occurs at the
site where the radiation energy is deposited.
Indirect action: 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.
 Indirect Action
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.
 Arrested Mitosis
Ionizing radiations also affect cell
division, resulting in arrested mitosis and,
consequently, in retardation of growth.
This phenomenon is the basis of
radiotherapy of neoplasms.
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
Cytoplasmic changes probably play
a minor role in arrested mitosis and
cell death.
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 are deleterious to
the person irradiated.
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.
Genetic effects are of no
consequence in persons who do not
procreate or who are in the post-
reproductive period of life.
 Somatic Effects
Somatic tissues do not always react
to doses of ionizing radiation so as to
give immediate clinically observable
effects. There may be a time-lapse
before any effects are seen.
Basically, somatic effects are
classified in two categories:
Acute or immediate effects
Delayed or chronic (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
 Variables in Somatic
Effects
Individual Variability. Certain
individuals are more sensitive or
resistant than others in their response
to radiation.
The expression, LD50 (30 days), is
frequently used in radiobiology which
means that a certain dose kills 50% of
the exposed animals within 30 days.
The 50% who survive are due to the
individual variability.
 Variables in Somatic
Effects
Species variability. The
phenomenon of species variability
is well known. The reason is not
well-understood.
 Variables in Somatic
Effects
Cellular and tissue variability. In 1907
Bergonie and Tribondeu advanced the first
generalization in radiobiology by stating
that "cells are sensitive to radiation in
proportion to their proliferative activity
and in inverse proportion to their degree
of differentiation.
Simply stated, it means that the rapidly
dividing cells are more sensitive to
radiation than more differentiated, slowly
dividing cells.
 Bergonie and Tribondeus
Axiom
One of the most notable exceptions
to this generalization is the
lymphocyte, not capable of
proliferative activity, is a
differentiated cell, and is one of the
most radiosensitive cells in the
body.
 Variables in Somatic
Effects
Total-body vs localized-area
exposure. A single radiation dose of
4.5-5.0 Gy may produce only erythema
of the skin if given to a localized part of
the body.
However, if the same dose is given to
the entire body, it will cause the death
of 50 percent of the people exposed.
This quantity of radiation is identified as
LD50, the lethal dose for 50 percent of
the people thus exposed
Variables in Somatic
Effects
Specific area protection
 Variables in Somatic
Effects
Total dose: The higher the dose of
radiation, the greater is the
probability and severity of occurrence
of biological effects.
 Variables in Somatic
Effects
Dose rate dependence: radiation dose
that would be lethal if given in a short time,
such as a few hours, may result in no
detectable effects if given in small
increments during a period of several years.
This is due to the ability of somatic cells to
repair damage caused by exposure to
radiation. However, tissues do not return to
their original state following radiation
damage, as there are some irreparable
alterations produced.
 Variables-Dose Rate
In general, it may be stated that
four-fifths of somatic damage is
repaired. But the irreparable damage
is cumulative. When this cumulative
damage reaches a high level, clinical
manifestations may appear.
 Variables-Dose Rate
Local somatic effect (Alexander,
p.149 Revised Edition)
 Dose-effect
Relationships
Threshold response: An increase in
radiation dose may not produce an
observable effect until the tissue has
received a minimal level of exposure called
the threshold dose.
Once the threshold dose has been
exceeded, increasing dose will demonstrate
exceeding observable tissue damage.
Cataract and erythema of skin are well-
known threshold responses
 Dose-effect
Relationships
Linear response: A linear dose-response
suggests that all exposure carries a certain
probability of harm and that the effects of
multiple small doses are additive.
The dose response curve for most radiation-
induced tumors is linear which implies that
there is no "safe" dose, i.e., no dose below
which there is absolutely zero risk.
Every exposure carries some risk.
 Dose-effect
Relationships
Linear-quadratic response
(curve)
A linear-quadratic response implies
lesser risk at lower dose rate than
linear response or when the
exposure is fractionated. However,
there is no safe dose.
 Variables in Somatic
Effects
Age.
"The radiosensitivity is very high in new-born
mammals; it decreases until full adulthood
is reached and then remains constant; old
mice (about 600 days) are again more
radiosensitive." (Bacq and Alexander, P.299)

"The embryo is . . . most sensitive during the

period of most active organ development,
which lasts from the second to the sixth
week after conception." (Alexander, p. 156
Revised Edition)
 Variables in Somatic
Effects
Sex
The female is more radioresistant in
some species possibly due to high
levels of estrogens, some of which
have radioprotective properties.
(Arena, p. 463)
 Variables in Somatic
Effects
Metabolism. The lower the
metabolic rate and the lower the
state of nutrition, the higher the
resistance of the organism to the
effects of radiation. Higher
metabolic rate seems to magnify
the radiation effect.
 Variables in Somatic
Effects
Linear Energy Transfer (LET)
The dose required to produce a
certain biological effect is reduced
as the LET of the radiation
increases. Thus alpha particles are
more efficient in causing biological
damage than low LET radiations.
 Variables in Somatic
Effects
Oxygen effect
The radioresistance of many
biological tissues increases 2 to 3
times when irradiation is conducted
with reduced oxygen (hypoxia).
 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.
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 X-
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 :
Teeth
Adult teeth:
very resistant to the direct effect of
radiation exposure.
no effect on the crystalline structure
of enamel, dentin and cementum.
Radiation caries: in individuals whose
salivary glands have been damaged
resulting in xerostomia. Secondary to
changes in saliva; i.e., reduced flow,
pH and buffering capacity and
increased viscosity.
 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).
The salivary changes influence oral
microflora, and, secondarily contribute to
the formation of radiation caries.
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.
Secondary infection by Candida albicans is a
common complication. 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
Life span shortening. Life span of
small laboratory animals can be
shortened by exposure to repeated
large doses of radiation.
If this phenomenon occurs among the
human beings is inconclusive.
 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
developmental
The first 2 weeks of pregnancy: most
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.
Embryological and
developmental
After organogenesis, effect is at the
tissue and cellular level rather, than
at the organ level; so that gross,
congenital anomalies are not to be
expected.
In general, a dose as small as 100
mGy may cause gross defects. In
Denmark, a therapeutic abortion is
recommended once it is determined
that the fetus has received 100 mGy
(or 100 mSv) 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.
A radiation dose of this magnitude is
not expected in any diagnostic
procedure, especially in dentistry.
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.
The denuded surface gets rapidly infected;
septicemia and death is an invariable
consequence.
 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 Effects
There is no controversy relative to
relationship of ionizing radiation
exposure and neoplasia production.
It is universally accepted that such
exposure increases incidence of tumors
in a great variety of tissues and organs.
It is important to appreciate that in the
U.S., almost 20 percent of deaths are
attributable to cancer (400,000 annually)
and a very small fraction of this total
number is due to radiation exposure.
 Stochastic Effects
A statistically significant increase in
cancer has not been detected in
populations exposed to doses less
than 50 mSv.
 Stochastic Effects-
Evidence
The largest group of individuals studied
are the Japanese atomic bomb survivors.
In the cohort of 86,572, there were 9,335
deaths from solid cancer between 1950
and 1997. Only 440 deaths were
estimated to be excess over spontaneous
incidence and were considered radiation-
induced cancer deaths (NCRP Report #
145).
During the same period, 87 leukemia
deaths can be attributed to radiation
exposure.
 Stochastic Effects-
Evidence
Other studies have followed over
14,000 British patients who
received spinal irradiations for
ankylosing spondylitis between
1935-1954.
36 cases of leukemia and 563
cases of cancer of other types have
been reported in these patients.
 Stochastic Effects-
Evidence
Patients receiving repeated
fluoroscopic examinations during
treatment of tuberculosis and
women treated with radiation for
postpartum mastitis between 1930-
1956 demonstrated a higher risk of
breast cancer.
 Stochastic Effects-
Evidence
Increased incidence of thyroid
cancer has been observed in
children who received radiation
therapy for enlarged thymus.
Breast cancer was also elevated in
these individuals.
 Stochastic Effects-
Evidence
Until the 1950s, X rays were used
to epilate children with tinia
capitis (ringworm infection of the
scalp) in Israel. Over 10, 000
children were exposed.
These children showed a higher
incidence of thyroid cancer as well
as brain tumors, salivary gland
tumors, skin cancer and leukemia.
 Stochastic Effects-
Evidence
Increased incidence of leukemia in
radiologists (as compared to non-
radiologic physicians) who practiced
before the radiation protection
methods were established.
Bone tumors in radium dial painters.
 Stochastic Effects-
Evidence
Higher incidence of lung cancer in
miners in Saxony who dug out the
ore from which the radium was
extracted.
Higher incidence of lung cancer
was also reported in uranium
miners in central Colorado
 Stochastic Effects-
Evidence
All patients in above studies
received exposures well above
diagnostic range.
The probability of diagnostic-dose
radiation-induced cancer
occurrence can only be estimated
by extrapolating from cancer rates
observed following exposures to
larger doses.
 Stochastic Effects-
Generalizations
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.
The mortality data for leukemia are
compatible with a linear quadratic dose
response relationship.
 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 X-
rays 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.
 Risk Estimation
Four agencies or bodies
comprehensively review, assess, or
estimate the radiation risk to
humans from exposure to ionizing
radiation and periodically publish
their findings in the form of reports.
These agencies are:
 Risk Estimation
1. The Biological Effects of Ionizing
Radiations (BEIR) Committee of the
U.S. National Research Council
2. International Commission on
Radiological Protection (ICRP)
3. National Council on Radiation
Protection and Measurements (NCRP)
4. United Nations Scientific Committee
on the Effects of Atomic Radiation
(UNSCEAR).
 Risk Estimation
Radiation induced tumors are clinically,
morphologically and biochemically indistinguishable
from those which occur spontaneously.
This implies that carcinogenic effects of radiation
may be demonstrated on statistical basis only; that
is, one may infer such action by the demonstration
of an excess in the number of cancers in the
irradiated population over the natural incidence.
Alternately, the probability of the cancer incidence
from a small dose is estimated by extrapolating from
cancer rates observed following exposure to large
doses.
Risk vs benefit