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Dr. Hassan M. Abouelkheir
BDS, Msc, PhD.
Linear: the response is directly related
to the dose.
Non-linear: the response is not
proportionate to the dose.
Threshold: the dose at which effects
are produced; below this dose, there
are no obvious effects.
Non-threshold: any dose produces a
Stochastic effect: occurs by chance, usually without a
threshold level of dose. The probability of a stochastic
effect is increased with increasing doses, but the
severity of the response is not proportional to the dose.
Genetic mutations and cancer are the two main
Deterministic effect: health effects that increase in
severity with increasing dose above a threshold level.
Usually associated with a relatively high dose delivered
over a short period of time. Skin erythema (reddening)
and cataract formation from radiation are two examples
of deterministic effects.
Radiation effects at the cellular level result from
changes in a critical or “target” molecule. This
target molecule is DNA (deoxyribonucleic acid),
which regulates cellular activity and contains
genetic information needed for cell replication.
The DNA molecule is called a chromosome.
Permanent changes in this molecule will alter
cell function and may result in cell death.
Direct vs. Indirect Effect
If an x-ray or some type of particulate radiation interacts
with the DNA molecule, this is considered a direct effect.
Particulate radiation, because of its mass, is more apt to
cause damage to the DNA by this direct effect. Other
molecules that contribute to cell function, such as RNA,
proteins, and enzymes, may also be affected by the direct
x-ray or particulate
Direct vs. Indirect Effect
Most of the damage to DNA molecules from x-rays is
accomplished through the indirect effect. When x-rays enter a
cell, they are much more likely to hit a water molecule because
there are a large number of water molecules in each cell. When
the x-ray ionizes the water molecule, ions and free radicals are
produced which in turn bond with a DNA molecule, changing its
structure. Since the x-ray interacted with the water molecule
before the DNA was involved, this is considered an indirect
x-ray or particulate
A free radical is an atom or molecule that has an
unpaired electron in the valence shell, making it highly
reactive. These free radicals aggressively join with the
DNA molecule to produce damage. In the presence of
oxygen, the hydroperoxyl free radical is formed; this is
one of the most damaging free radicals that can be
produced. Free radicals are the primary mediator of the
indirect effects on DNA.
Radiolysis of water:
As a result of the living body consists of
70- 90% water . So ionization of pure
water leads to fast moving free electron
and +ve charged molecule.
Both peroxyl radicals and hydrogen
peroxide are oxidizing agents that alter
biological molecules and cause cell
DNA is more radiosensitive than RNA.
1. Change or loss of base.
2. Disruption of hydrogen bonds
between DNA strands.
3. Breakage of one or both DNA strands.
4. Cross-linkage of DNA strands within
the helix to other DNA or proteins.
Cells undamaged: ionization alters the structure of
the cells but has no overall negative effect.
Sublethal injury: cells are damaged by ionization
but the damage is repaired.
Mutation: cell injury may be incorrectly repaired,
and cell function is altered or the cell may
reproduce at an uncontrolled rate (cancer).
Cell death: the cell damage is so extensive that the
cell is no longer able to reproduce.
Sublethal Injury: Cellular Repair
1. Ionization causes damage to DNA
(single-strand break of DNA).
2. Cellular enzymes recognize the damage and
coordinate the removal of the damaged section.
3. Additional cell enzymes organize replacement of the
damaged section with new material.
More damage results when the cell is irradiated during the G1/early
S portion of the cell cycle (before DNA synthesis); the damaged
DNA (chromosome) will be duplicated during DNA synthesis and
will result in a break in both arms of the chromosome at the next
G1 = gap phase 1 in which nuclear
components are replicated
S = synthesis phase; DNA is synthesized
during the last 2/3 of this phase
G2 = gap phase 2, a preparatory stage to
M = mitosis, during which cells divide
Cell most sensitive to
Cells that are more easily damaged by radiation are
radiosensitive. The characteristics of radiosensitive cells are:
1. High reproductive rate (many mitoses)
2. Undifferentiated (immature)
3. High metabolic rate
Lymphocytes, germ cells, basal cells of skin and mucosa,
and erythroblasts are examples of radiosensitive cells.
Cells that are not as susceptible to damage from radiation are
radioresistant. The characteristics of radioresistant cells are:
1. Low reproductive rate (few mitoses)
2. Well differentiated (mature)
3. Low metabolic rate
Nerve and muscle cells are examples of radioresistant cells.
It causes inhibition of cell division.
cytoplasm: It causes increased permeability to
potassium and Na- ions and changes in active
transport mechanisms. Nucleus is more
sensitive than cytoplasm. The sensitive site
in the nucleus is DNA within chromosomes.
Chromosome Aberrations: are observed when
DNA condenses to form chromosomes at the
time of mitosis.
Irradiation to rapidly dividing cells such as
hematopoietic tissues causes reduction in the
size of the irradiated tissue as a result of mitotic
delay and cell death.(usually during mitosis).
3 mechanisms are responsible for reproductive
1- DNA Damage: causes chromosomal
cell death after few mitosis
2- Bystander Effect:
Irradiated cells damaged by release molecules that
kill nearby cells . This bystander effect occur upon
irradiation by α particles & x-rays .
This causes cell killing, gene mutations and
3- Apoptosis: a programmed cell death without
necrosis . Cells round up, draw away from their
neighbors and condense nuclear chromatin.
Recovery: cell recovery from DNA damage and by
stander effect involves enzymatic repair of single –
strand breaks of DNA. Specially multiple
infractionated dose .
Radiosensitivity of a tissue or organ is
measured by its response to irradiation.
Small number of lost cells--> no clinical effect.
Large no. of lost cells-->clinical effect.
The dose + amount of cell loss ->deterministic effect.
Effects seen in first days or weeks are
determined by sensitivity of tissue
parenchymal cells. High radiosentive cells
as bone marrow or mucous membrane
effects can be seen quickly. Rather than
relativily radiosensitive cells as muscles.
Effects that seen after months or years from
exposure are loss of parenchymal cells and
replaced by fibrous connective tissue.
It is caused by death of replicating cells and bt
damage to the fine vasculature.
Both radiosensitive and radioresistant
parenchymal cells will be replaced by fibrous
The biological response to radiation is
dependent on several different factors.
1- Total Dose: the higher the radiation dose, the
greater the potential cellular damage.
2- Dose Rate: A high dose given over a short
period of time (or all at once) will produce more
damage than the same dose received over a
longer period of time.
3- Oxygen Effect: Radiation effects are more
pronounced in the presence of oxygen.
Oxygen is required for the formation of
the hydroperoxyl free radical, which is the
most damaging free radical formed
4-Linear Energy Transfer: This measures the
rate of the loss of energy as radiation moves
through tissue. Particulate radiation (alpha
particles, electrons, etc.) has a higher LET
because it has mass and interacts with
tissues much more readily than do x-rays.
Treating radiosensitive oral malignant tumors
depends on many factors such as radiosensitivity
, histology, size, location, invasion into adjacent
structures and duration of symptomatology.
Fractionation of total x-ray dose into multiple
small doses is better to increase cellular repair
and O2 tension in irradiated tumor make it more
A- Oral mucous membrane:
1. Redness and inflammation of
2. White to yellow
3. At the end of therapy sever
discomfort and difficulty to
4. Dry infection with candida
5-Healing within 2 months.
They are sensitive to radiotherapy.
Patient feels loss of taste during 2nd or 3rd
week of radiotherapy.
Irradiation to posterior 21/3 of tongue affect
bitter and acid flavors while anterior 1/3 affect
sweet and salt flavors.
Recovery takes about 60 to 120 days after
The parotid salivary glands are
more radiosensitve rather than
Acute inflammatory response soon
Chronic inflammatory progression
leads to progressive fibrosis,
adiposis, loss of fine vasculature
After few weeks of radiotherapy ,salivary
flow decrease to zero at 60 Gray.
Dryness of mouth usually subsides in 6 to
12 months because of cmpensatory
hypertrophy of residual salivary gland
Xerostomia beyond a year is less likely to
show significant return of function.
Irradiation of teeth during their development
retards their growth.
If it precedes calcification it may destroy tooth
bud . After calcification it may inhibit cellular
differentiation causing malformation and
arresting general growth.
Children receiving radiation therapy shows
defects in permanent dentition such as retarded
root development or missing 1 or 2.
It is a rampant form of dental
decay result from radiotherapy
of salivary glands leading to
xerostomia which causes caries
a. Reduced salivary flow.
B. Decreased pH.
C. Reduced buffering capacity.
D. Increased viscosity.
3 types of radiation caries;
1. Wide spread superficial
lesions attacking buccal,
occlusal , incisal and palatal
2. Cirumferentially cervically
involving dentine and
3. Dark pigmentation of
entire crown and incisor
edges may be worn.
A. Daily application of 1% Na F gel
B) Reduce streptococcus mutans &
C. Oral hygiene instructions.
D. Restorative dental procedures.
The primary damage of mature bone due
to damage of fine vasculature specially in
mandible rather than maxilla.
The marrow tissue becomes hypovascular,
hypo toxic and hypo cellular with
replacement of normal marrow with fatty
marrow of fibrous C.T.
In non-healing wound as result of
extraction wound or denture sore
breaking of mm leading to
infection and necrosis of bone so
It is recommended to do
extraction & alveolectomies 2
to 3 weeks before irradiation .
This allow time for healing.
must be accompanied with
alveolectomy to protect
mucosa from trauma of
prosthetic appliance and
preferred with hyperbaric
Acute Radiation syndrome:
! it is a collection of the
signs and symptoms as a
result of radiotherapy,
atom bomb blasts and
! It ranges from prodromal
symptoms to hematopoietic,
cardiovascular & CNS
Embryonic cell are highly
radiosensitive as they
and rapidly mitotic.
During periods of
implantation [10-14] days
after conception in humans
embryo may show
Organogenesis period [18-45 of gestation] is
the most sensitive period .
It causes growth retardation , microcephaly
and mental retardation.
1. Most cancer appear 10 years after exposure.
2. Childhood risk exposure is twice as large as
3. The mortality rate show no linearity below
4.Cancer due to radiation is multiple of
Incidence of leukemia
rises following exposure
to radiation from 5-30
Children under 20 are
more at risk than adults.
Dental radiographic examination carries
certainly small risk. This could be reduced by
using E-speed film and rectangular
The highest estimated risk from leukemia &
for thyroid & bone surface cancers.
The panoramic radiography carries one tenth
the risk of full mouth radiogaphy.
Growth and development:
Children exposed to bombing
showing reduced height, weight &
There is 4% chance of mental
retardation per 100 MSV at 8-15
weeks of gestational age.
The threshold for induction of
cataracts ranges from 2-5Gray in
single or multiple dose.
Radiation genetic damage
may induce new genetic
mutation rather than
spontaneous mutations in
There is no threshold dose
below which there is no
damage to offspring in
In humans the genetic
doubling dose for mutations
resulting in death is
Radiation genetics (cont.):
In humans the genetic doubling dose for
mutations resulting in death is
The gonadal dose to patients from full
mouth radiographic examination is in the
range of 2-30µSV.
The estimated genetic effects resulting
from 10MSV per generation.