Radiation biology

RADIATION BIOLOGY
A.KUMAR
PG STUDENT
ORAL MEDICINE AND RADIOLOGY

CONTENTS
 INTRODUCTION
 RADIATION MEASUREMENTS
 RADIATION INJURY
 Terminologies
 TYPES OF RADIATION EFFECTS
Stochastic effects
Deterministic (non-stochastic) effects
Short term effects (acute)
Long term effects (chronic)
Somatic effects (late)
Genetic effects
In-Utero Effects
 Factors determine biological effects of radiation

 BIOLOGICAL EFFECTS
EFFECT ON CELLS
1.DNA
2.CYTOPLASM
3.NUCLEUS
4.CHROMOSOMES
5.PROTEINS
6.CELL DIVISION
7.CELL DEATH
RADIATION EFFECT ON CRITICAL ORGANS
1.SKIN
2.BONE MARROW
3.THYROID
4.GONADAL
5.EYE
EFFECT ON ORAL TISSUES
1.ORAL MUCOSA-MUCOSITIS
2.TASTE BUDS
3.SALVARY GLANDS-XEROSTOMIA
4.TEETH- RADIATION CARIES
5.BONES-OSTEORADIO NECROSIS
EFFECT ON WHOLE BODY
1.ACUTE RADIATION SYNDROME
2.HEMATOPOITIC SYNDROME
3.GASTROINTESTINAL SYNDROME
4.CARDIOVASCULAR SYNDROME
5.CENTRAL NERVOUS SYNDROME

RADIATION BIOLOGY
Radiation biology is the study of the effects of
ionizing radiation on living systems.

RADIATION
• Radiation, as defined as the emission and
propagation of energy through space or a
substance in the form of waves or particles.
• IONIZING RADIATION
• NON-IONIZING RADIATION

Ionizing Radiation
• Ionizing radiation can be defined as radiation that is
capable of producing ions by removing or adding an
electron to an atom.
• Ionizing radiation can be classified into two groups:
• (1) particulate radiation
• (2) electromagnetic radiation.

ELECTROMAGNETIC RADIATION
• Electromagnetic radiation can be defined as the
propagation of wave like energy (without mass)
through space or matter.

RADIATION MEASUREMENTS
• Radiation can be measured in the same manner as other physical
concepts such as time, distance, and weight.
• International Commission on Radiation Units and Measurement
(ICRU) has established special units for the measurement of radiation.
• Such units are used to define four quantities of radiation:
 (1) exposure.
 (2) dose.
 (3) dose equivalent.
 (4)Radioactivity
• At present, two systems are used to define radiation measurements:
(1) The older system is referred to as the traditional system, or
standard system.
(2) the newer system is the metric equivalent known as the SI system.

EXPOSURE
 EXPOSURE;The term exposure refers to the measurement of ionization in air
produced by x-rays.
Standard unit-Roentgen (R)
SI unit -Coulombs per kilogram (C/kg)
One roentgen is equal to the amount of radiation that produces approximately two
billion, or 2.08 × 10 9 , ion pairs in one cubic centimeter (cc) of air.

DOSE
 DOSE;Dose can be defined as the amount of energy absorbed by a tissue.
Standard unit-Radiation absorbed dose (rad)
SI unit -Gray (Gy)
Rad: A special unit of absorbed dose that is equal to the
Deposition of 100 ergs of energy per gram of tissue (100erg/g).

DOSE EQUIVALENT
 DOSE EQUIVALENT;Different types of radiation have different effects
on tissues.The dose equivalent measurement is used to compare the
biologic effects of different types of radiation.
Standard unit-Roentgen equivalent (in) man (rem)
SI unit -Sievert (Sv)

RADIOACTIVITY
• It is the process by which a nucleus of an unstable atom
loses energy by emitting ionizing radiation.
Standard unit-Curie(Ci)
SI unit -Becquerel(Bq)
• One Curie is equal to 3.7x1010 (37 Billion Bq)disintegrations
per second.
• One Becquerel is equal to one disintegration per second.
• DPS-The number of subatomic particles (e.g. alpha
particles) or photons (gamma rays) released from the
nucleus of a given atom over one second

RADIATION INJURY
• Radiation injury- tissue damage or changes caused by
exposure to ionizing radiation-namely, gamma and x-rays
such high-energy particles as neutrons, electrons, and
positrons.
• In diagnostic radiography, not all x-rays pass through the
patient and reach the dental x-ray film; some are absorbed
by the patient’s tissues.
• Absorption
refers to the total transfer of energy from the x-ray photon
to patient tissues.

Mechanisms of radiation
injury
Two specific mechanisms of radiation injury are possible:
(1)ionization
(2)free radical formation

IONIZATION
• X-rays are a form of ionizing radiation; when x-rays strike patient
tissues, ionization results.
• ionization is produced through the photoelectric effect or Compton
scatter and results in the formation of a positive atom and a
dislodged negative electron.
• The ejected high-speed electron is set into motion and interacts with
other atoms within the absorbing tissues. The kinetic energy of such
electrons results in further ionization, excitation, or breaking of
molecular bonds, all of which cause chemical changes within the cell
that result in biologic damage

FREE RADICALS FORMATION
• X-ray causes cell damage primarily through the formation
of free radicals. Free radical formation occurs when an x-ray
photon ionizes water, the primary component of living
cells.
• Ionization of water results in the production of hydrogen
and hydroxyl free radicals
• A free radical is an uncharged (neutral) atom or molecule
that exists with a single, unpaired electron in its outermost
shell.

Theories of Radiation Injury
• Two theories are used to describe how radiation
damages biologic tissues:
• (1) Direct or Target Action Theory
• (2 Indirect Action or Poison Chemical Theory

Direct or Target Action Theory
• The direct theory of radiation injury suggests that cell
damage results when ionizing radiation directly hits critical
areas, or targets, within the cell.
• For example, if x-ray photons directly strike the DNA of a
cell, critical damage occurs, causing injury to the irradiated
organism.
• Direct injuries from exposure to ionizing radiation occur
infrequently; most x-ray photons pass through the cell and
cause little or no damage.

Indirect Action or Poison
Chemical Theory
 x-ray photons are absorbed by the water within a cell, free
radicals are formed. These free radicals combine to form
toxins.
(e.g., H 2 O 2 ), which cause cellular dysfunction and
biologic damage.
 The chances of free radical formation and indirect injury
are great because cells contain 70% to 80% water.

Sequence of Radiation Injury
• Chemical reactions (e.g., ionization, free radical formation) that
follow the absorption of radiation occur rapidly at the molecular
level.
• However, varying amounts of time are required for these changes to
alter cells and cellular functions.
• As a result, the observable effects of radiation are not visible
immediately after exposure. Instead, following exposure, a latent
period occurs.
• A latent period can be defined as the time that elapses between
exposure to ionizing radiation and the appearance of observable
clinical signs.

• After the latent period, a period of injury occurs. A variety of cellular
injuries may result, including cell death, changes in cell function,
breaking or clumping of chromosomes, formation of giant cells,
cessation of mitotic activity, and abnormal mitotic activity.
• The last event in the sequence of radiation injury is the recovery
period. Not all cellular radiation injuries are permanent. With each
radiation exposure, cellular damage is followed by repair. Depending
on a number of factors, cells can repair the damage caused by
radiation.
• If effects of radiation exposure are additive, the unrepaired damage
accumulates in the tissues. The cumulative effects of repeated
radiation exposure can lead to health problems (e.g., cancer, cataract
formation, birth defects).

Terminologies
• LINEAR ENERGY TRANSFER (LET)
• RELATIVE BIOLOGIC EFFECTIVENESS(RBE)
• LATENT PERIOD
• MAXIMUM PERMISSIBLE DOSE
• MAXIMUM ACCUMULATED DOSE
• TOTAL DOSE
• DOSE RATE
• MEDIAN LETHAL DOSE

LINEAR ENERGY TRANSFER (LET)
 Amount of energy is transferd from
ionizing radiation to soft tissue
36

RELATIVE BIOLOGIC
EFFECTIVENESS(RBE)
Biologic response compared with
two types of radiation
37

LATENT PERIOD
• THE TIME LAPSE BETWEEN EXPOSURE OF THE RADIATION
AND THE APPEARENCE OF THE EFFECTS
38

maximum permissible dose
• Greatest dose of radiation which is not expected to cause detectable
bodily injury to people at any time during their lifetime.
• The amount of ionizing radiation a person may be exposed to
supposedly without being harmed
• The limits of ionizing radiation set for radiation workers and the
general public by the International Commission on Radiological
Protection. For radiology workers this limit for the whole body is 50
mSv.

Maximum Accumulated Dose
• Occupationally exposed workers must not exceed an
accumulated lifetime radiation dose. This is referred to as
the maximum accumulated dose (MAD). MAD is
determined by a formula based on the worker’s age. To
determine the MAD for an occupationally exposed person,
the following formula is used:
• MAD=(N-18)x5 rems/ year
• MAD=(N-18)x0.05 Sv/ year
• where N refers to the person’s age in years. (Note that the
number 18 refers to the minimum required age of a person
who works with radiation.)

• Total dose: Quantity of radiation received, or the total amount of
radiation energy absorbed. More damage occurs when tissues absorb
large quantities of radiation.
• Dose rate: The amount administered radiation per unit of time.
(dose rate = dose/time).
More radiation damage takes place with high dose rates because a
rapid delivery of radiation does not allow time for the cellular damage
to be repaired.
• When organisms are exposed at lower dose rates, a greater
opportunity exists for repair of damage, thereby resulting in less net
damage.

median lethal dose
 The amount of ionizing radiation that will kill 50
percent of a population in a specified time
Abbreviation: LD50

Stochastic effects
• Stochastic effects are those that may develop.Their development is
random and depends on the laws of chance or probability. Examples
of somatic stochastic effects include leukaemia and certain tumours.
• These damaging effects may be induced when the body is exposed to
any dose of radiation.
• Experimentally it has not been possible to establish a safe dose — i.e.
a dose below which stochastic effects do not develop. It is therefore
assumed that there is no threshold dose, and that every exposure to
ionizing radiation carries with the possibility of inducing a stochastic
effect.
• However, the severity of the damage is not related to the size of the
inducing dose. This is the underlying philosophy behind present
radiation protection recommendations.

deterministic effects
• Nonstochastic effects (deterministic effects) are somatic
effects that have a threshold and that increase in severity
with increasing absorbed dose.
• Examples of nonstochastic effects include erythema, loss of
hair, cataract formation, and decreased fertility.
• Compared with stochastic effects,deterministic effects
require larger radiation doses to cause serious impairment
of health.

Short-Term Effects
• Following the latent period, effects that are seen within
minutes, days, or weeks are termed short-term effects.
Short-term effects are associated with large amounts of
radiation absorbed in a short time (e.g., exposure to a
nuclear accident or the atomic bomb).
• Acute radiation syndrome (ARS) is a short-term effect and
includes nausea,vomiting, diarrhea, hair loss, and
hemorrhage.
• Short-term effects are not applicable to dentistry.

Long-term effects
• Effects that appear after years, decades, or generations are
termed long-term effects.
• Long-term effects are associated with small amounts of
radiation absorbed repeatedly over a long period. Repeated
low levels of radiation exposure are linked to the induction
of cancer, birth abnormalities, and genetic defects.

Somatic and Genetic Effects
• All the cells in the body can be classified as either somatic
or genetic.
• Somatic cells are all the cells in the body except the
reproductive cells.
• The reproductive cells (e.g., ova, sperm) are termed
genetic cells.
• Depending on the type of cell injured by radiation, the
biologic effects of radiation can be classified as somatic or
genetic.

somatic effects
• Somatic effects are seen in the person who has been
irradiated. Radiation injuries that produce changes in
somatic cells produce poor health in the irradiated
individual.
• Major somatic effects of radiation exposure include the
induction of cancer, leukemia, and cataracts.
• These changes, however, are not transmitted to future
generations

Genetic effects
• Genetic effects are not seen in the irradiated person but are passed
on to future generations. Radiation injuries that produce changes in
genetic cells do not affect the health of the exposed individual.
• Instead, the radiation-induced mutations affect the health of the
offspring .
• Genetic damage cannot be repaired.
• Doubling dose: dose of radiation expected to double the number of
genetic mutations in a generation.(or) Amount of radiation that
doubles the incidence of stochastic effects.
• Human data from Hiroshima/Nagasaki suggest somewhat average
doubling dose is 1.6 Sv

Effects on the unborn child
• The developing fetus is particularly sensitive to the effects of
radiation, especially during the period of organogenesis (2–9
weeks after conception).
• Exposures in the range of 2 to 3 Gy during the first few days
after conception are thought to cause undetectable death of
the embryo.
• The period of maximal sensitivity of the brain is 8 to 15 weeks
after conception.
• The major problems are:
1.Congenital abnormalities or death associated with large
doses of radiation
2.Mental retardation associated with low doses of radiation.
 As a result, the maximum permissible dose to the abdomen of a
woman who is pregnant is regulated by law.

Factors determine biological
effects of radiation
 1. Nature of tissue irradiated.
i. Radioresponsive.
ii. Radioresistant.
 2. Area irradiated:
For the same dose, if a smaller area is irradiated, the effect of radiation is less.
 3. Rate of dose:
Smaller the dose, distributed over a large period of time results in a smaller or
lesser effect of the radiation.
 4. Fractionization:
Division of the dose, with sufficient gaps, helps in tissue recovery resulting in
lesser effect of the radiation.
 5. Latent period:
This is the period between the time of irradiation and the appearance of the
effect.
 6. Age of the patient:
Younger the patient greater the chances of recovery.

CONT….
 7. Recovery power of the tissue:
Undifferentiated cells have a greater power of recovery.
 8. Type of cell:
The effect of radiation is seen in the same generation if a somatic cell is effected,
and in case of the genetic cell the effect of radiation will be seen in the next
generation.
 9. Type of irradiation:
There are different types of irradiations—low energy, high energy or linear
energy transfer.
 10. Stage of development of the tissue:
The effect of irradiation depends on the stage of development of the tissue,
e.g. primitive and undifferentiated and still undergoing mitosis when irradiated the
damage caused is greater.

CONT…
 11. Tissue threshold:
Greater the tissue threshold,lesser the damage seen. This depends on the amount of
radiation absorbed. Somatic changes do not occur until a minimum of tissue threshold is
exceeded. Genetic changes occur with any given dose.
 12. Species and individuals:
Different species respond differently. The median lethal dose varies in different
species. Similarly in individuals of the same species the response may be variable. This
variation of the Maximum Permissible Dose is approximately 50 percent.
 13. Oxygenation:
Greater oxygenation of the tissue,chances of recovery are greater, e.g. hyperbaric
oxygen is used to treat osteoradio necrosis.
• The presence of oxygen in a cell acts as a radiosensitizer, making the effects of the
radiation more damaging. Tumor cells typically have a lower oxygen content than
normal tissue.
• This medical condition is known as tumor hypoxia and therefore the oxygen effect acts
to decrease the sensitivity of tumor tissue. Generally it is believed that neutron
irradiation overcomes the effect of tumor hypoxia, although there are
counterarguments.

 BIOLOGICAL EFFECTS
EFFECT ON CELLS
1.DNA
2.CYTOPLASM
3.NUCLEUS
4.CHROMOSOMES
5.PROTEINS
6.CELL DIVISION
7.CELL DEATH
RADIATION EFFECT ON CRITICAL ORGANS
1.SKIN
2.BONE MARROW
3.THYROID
4.GONADAL
5.EYE
EFFECT ON ORAL TISSUES
1.ORAL MUCOSA-MUCOSITIS
2.TASTE BUDS
3.SALVARY GLANDS-XEROSTOMIA
4.TEETH- RADIATION CARIES
5.BONES-OSTEORADIO NECROSIS
EFFECT ON WHOLE BODY
1.ACUTE RADIATION SYNDROME
2.HEMATOPOITIC SYNDROME3.
3.GASTROINTESTINAL SYNDROME
4.CARDIOVASCULAR SYNDROME
5.CENTRAL NERVOUS

 Single strand break can repair
 Double strand break is responsible for
.mutation
.cell death
.carcinogenisis
Point mutations: Effect of radiation on
individual genes is referred to as point
mutation.

CYTOPLASM
 Increased permeability of plasma membrane to sodium
and potassium ions.
 Swelling and disorganization of mitochondria.
 Focal cytoplasmic necrosis.

NUCLEUS
Nucleus is more radiosesitive than the cytoplasm

PROTEINS
 Denaturation.
 primary structure of the protein is usually not significantly altered
 secondary and tertiary stuctures are effected by breakage of
hydrogen or disulfide bonds
 Inactivation of enzymes sometimes occures.

MITOCHONDRIA
• Mitochondria demonstrate –
• .Increased permeability
• .swelling
• .Disorganization of the internel cristae

Chromosome Aberrations
 If radiation exposure occurs after DNA synthesis (I,e G2 or
late s)only one arm of the effected chromosome is broken
 If radiation occurs before DNA synthesis (G1 or early S)
both arms are effected

 The survivors of the atomic bombings of Hiroshima and
Nagasaki have demonstrated chromosome aberrations in
circulating lymphocytes more than two decades after the
radiation exposure.

EFFECTS ON CELL REPLICATION
Mild dose-mild mitotic delay
Moderate dose-longer mitotic delay
Severe dose-profound delay with incomplete recovery

CELL DEATH
 Reproductive death in a cell population is loss of the capacity for
mitotic division. The three mechanisms of reproductive death are
 DNA damage,
 Bystander effect
 Apoptosis.

DNA DAMAGE
 Single strand break can repair
 Double strand break is responsible for
• .mutation
• .cell death
• .carcinogenisis

Bystander effect
 It is the phenomenon in which unirradiated(normal) cells exhibit
irradiated effects as a result of signals received from nearby
irradiated cells.
 This bystander effect has been demonstrated for both α particles and
x rays and causes chromosome aberrations, cell killing, gene
mutations, and carcinogenesis.
 The abscopal effect is a phenomenon where the response to
radiation is seen in an area distant to the irradiated area, that is, the
responding cells are not juxtaposed(close) with the irradiated cells. T-
cells and dendritic cells have been implicated to be part of the
mechanism.
 In suicide gene therapy, the "bystander effect" is the ability of the
transfected cells to transfer death signals to neighboring tumor cells.

APOPTOSIS
 Leaves falling from tree
 Also known as’ programmed cell death’
 Apoptosis is particularly common in hemopoietic and
lymphoid tissues.

RADIATION EFFECT ON CRITICAL
ORGANS
 In dental radiography the critical organs receiving scattered
radiation include:
 SKIN
 BONE MARROW
 THYROID
 GONADAL
 EYE

 1. Skin: The reaction of the skin to radiation may be categorized as:
i. Early or acute signs:
• Increased susceptibility to chapping.
• Intolerance to surgical scrub.
• Blunting and leveling of finger ridges.
• Brittleness and ridging of finger nails.
ii. Late or chronic signs:
• Loosening of hair and epilation.
• Dryness and atrophy of skin, due to destruction of the sweat glands.
• Progressive pigmentation, telangiectasis and keratosis.
• Indolent type of ulcerations.
• Possibility of malignant changes in tissue.

 All these changes in the skin are due to radiation
trauma to:
1-The blood vessels.
2- Connective tissue.
3- Epithelium.
• Early erythema may appear from a single dose of
about 450 rads.
• With lower doses no erythema occurs.

BONE MARROW
• 13 mR for full mouth intraoral periapical radiographs.
• A maximum dose of 200 R is required for any damage to
the marrow or blood forming organs.
• Hence, the risk of bone marrow damage from dental X-rays
is small.
• The primary somatic risk from dental radiography is
leukemia induction,especially in young individuals.
• This is because at birth all bones contain only red bone
marrow. younger individuals are at a greater risk of
developing leukemia.

 THYROID
40 mR for full mouth intraoral periapical radiographs.
A dose of 10 R will produce thyroid cancer.
 Gonadal – a single intraoral radiograph gives 100 to 900 mR to the
face.
From this;
Male gonads receive 0.3 mR.
Female gonads receive 0.03 to 0.001 mR,
 Eye – a series of full mouth intraoral periapical radiographs, will give
only a few mR.
Cataract of the lens is produced after 500 R of exposure.

RADIATION EFFECT ON ORAL
TISSUES
• ORAL MUCOUS MEBRANE
• TASTE BUDS
• SALIVARY GLANDS
• RADIATION CARIES
• OSTEORADIO NECROSIS
94

ORAL MUCOUS MEMBRANE
• Pre-radiation Therapy Management Considerations
• A. A complete dental examination to identify
preexisting problems.
• B. Prior to treatment, potentially complicating
diseases should be corrected
• C. Patient adherence to hygiene protocols are critical

Mucositis
• Describes inflammation of oral mucosa resulting from
chemotherapeutic agents or ionizing radiation,Typically manifests as
erythema or ulcerations.
• May be exacerbated by local factors.
• Dysgeusia, or an alteration in taste perception
• Red,shiny, or awollen mouth and gums
• Blood in the mouth
• Sores in mouth,gums and tongue
• Difficulty swallowing or talking
• Soft, whitish patches in the mouth and tongue
• Increased mucous or thicker saliva

Pathophysiology
• The pathophysiology of mucositis can be divided into
its 5 stages
1-initiation phase
2-message generation phase
3-signaling and amplification phase
4-ulceration phase
5-healing phase

Management of mucositis
• Good oral hygiene.
• Avoidance of spicy, acidic, hard, and hot foods and
beverages.
• Use of mild-flavored toothpastes.
• Use of saline-peroxide mouthwashes 3 or 4 times per day.
• Bland rinses:
– 0.9% saline solution.
– Sodium bicarbonate solution.

• Topical anesthetics:
– Lidocaine: viscous, ointments, Sprays.
– Benzocaine: sprays, gels.
– 0.5% or 1.0% dyclonine hydrochloride (HCl).
– Diphenhydramine solution.
• Mucosal coating agents:
– Amphojel.
– Kaopectate.
– Hydroxypropyl methylcellulose film-forming agents (e.g., Zilactin).
– Gelclair-Bioadherent (approved by the U.S. Food and Drug
Administration [FDA]
• Analgesics:
– Benzydamine HCl topical rinse
– Opioid drugs: oral, intravenous (e.g., bolus, continuous infusion,
patient-controlled analgesia [PCA]), patches, transmucosal.

TISSUES
• TASTE BUDS
• SALIVARY GLANDS
102

TASTE BUDS
• These are sensitive to radiation and patient realizes a loss
of taste in the second or third week of radiation therapy.
• Radiation directed to the mouth will affect taste buds
located on the tongue. Foods may taste differently to you
or you may have a temporary aversion to some foods. It
may take 2 or 3 months or more before your taste
sensations return.
• The tongue's lining and taste buds are susceptible to
radiation. A decrease in saliva also causes changes in taste.
• It is common to have an increased sensitivity to sour and
bitter taste,or to have a “metallic” taste in your mouth
• Changes in taste may cause you to lose your appetite.

MANAGEMENT
• At this time, there is no treatment for
taste changes.
• Research has shown that taking zinc
sulfate during treatment may be helpful
in expediting the return of taste after
head and neck irradiation.

• Try these tips to help reduce the impact of taste changes on
your ability to get good nutrition and avoid weight loss.
• Do not eat 1-2 hours before chemotherapy and up to 3 hours
after therapy. It is common to develop a taste aversion to
foods eaten during this time, so it is particularly important to
avoid your favorite foods.
• Rinse mouth with water before eating.
• Eat small, frequent meals and healthy snacks.
• Eat meals when hungry rather than at set mealtimes.
• Have others prepare the meal.

• Substitute poultry, fish, eggs and cheese for red meat.
• Eat meat with a marinade or sauce; try something sweet.
• Use plastic utensils if food tastes like metal.
• Use mints, lemon drops or chewing gum to mask the bitter
or metallic taste.
• Chilled or frozen food may be more acceptable than warm
or hot food.
• Try tart foods, such as citrus fruits or lemonade, unless you
have mouth sores.
• Avoid bad odors, as these may affect your appetite.

TISSUES
• TASTE BUDS
• SALIVARY GLANDS
108

SALIVARY GLANDS
• Parotid gland is more radio sensitive than the other glands
• Increase the growth of st.mutans,lactobacillous,candida
• Decrease the ph leads to decalcification of enamel
• Difficult to swallow(DISPHAGIA)
• Decrease salivary secretion(XEROSTOMIA)
• The parenchymal component of the gland is sensitive to
radiation. The gland demonstrates progressive fibrosis
adiposis, loss of fine vasculature and simultaneous
parenchymal degeneration.

• There is marked decrease in the salivary flow.
• The composition of saliva is affected.
• There is increased concentration of sodium,chloride,
calcium, magnesium ions and proteins.
• The saliva loses its lubricating properties.
• The mouth becomes dry and tender due to xerostomia.
• The pH of saliva is decreased which may initiate
decalcification of enamel.
• A compensatory hypertrophy of the salivary gland may take
place and the xerostomia may subside after six to twelve
months after therapy.

• In recent years, doctors have found that newer forms of
radiation therapy may work better than the standard treatment.
• Accelerated hyperfractionated radiation therapy: In this
approach, radiation is given twice a day over a shorter total
length of time.
• Three-dimensional conformal radiation therapy (3D-CRT): 3D-
CRT uses the results of imaging tests such as MRI and special
computers to precisely map the location of the tumor.
• Several radiation beams are then shaped and aimed at the
tumor from different directions. Each beam alone is fairly weak,
which makes it less likely to damage normal tissues, but the
beams converge at the tumor to give a higher dose of radiation
there.

• Intensity modulated radiation therapy (IMRT): IMRT is an advanced
form of 3D therapy. It uses a computer-driven machine that actually
moves around the patient as it delivers radiation.
• In addition to shaping the beams and aiming them at the tumor from
several angles, the intensity (strength) of the beams can be adjusted
to limit the dose reaching the most sensitive nearby normal tissues.
• Many major hospitals and cancer centers now use IMRT as the
standard way to deliver external beam radiation.
• Fast neutron beam radiation: Instead of using x-rays, neutron
radiation therapy uses a beam of high-energy neutrons. Neutrons are
neutral particles in atoms. Some studies have suggested that this type
of radiation may be more effective, but it may also lead to more side
effects. Neutron therapy machines are available in only a handful of
cancer centers in the United States at this time.

• A neutron radiotherapy facility would probably cost $20 to
$25 million dollars today.
• Neutron therapy is especially good at controlling salivary
gland cancer at the tumor site and in the same region.
Neutron therapy also works best on tumors below 4
centimeters in diameter, controlling about 80 percent of
tumors this size. But it is used with success on many larger
tumors as well.

TISSUES
• TASTE BUDS
• SALIVARY GLANDS
• TEETH(RADIATION CARIES)
115

Teeth
• Evidence in changes of crystalline structure of enamel, dentin, or
cementum following RT is unclear.
• Pulp shows decrease in vascular elements, with accompanying
fibrosis and atrophy.
• Pulpal response to infection, trauma, and various dental procedures
appears compromised.
Level as low as 2500 cGy can have marked effect on tooth
development.
Exposure
• before calcification completion - tooth bud may be damaged .
• At later stage of development - may arrest growth.

• Children receiving radiation therapy to the jaws may show
defects in the permanent dentition such as retarded root
development, dwarfed teeth, or failure to form one or more
teeth
• If exposure precedes calcification, irradiation may destroy the
tooth bud. Irradiation after calcification has begun may inhibit
cellular differentiation,causing malformations and arresting
general growth.
• Eruptive mechanism of teeth is relatively radiation resistant
• Adult teeth are resistant to the direct effects of radiation
exposure.
• Radiation has no direct effect on the crystalline structure of
enamel, dentin, or cementum, and radiation does not increase
their solubility.

• Radiation caries is a rampant form of dental decay that may
occur in individuals who receive a course of radiotherapy
that includes exposure of the salivary glands.
• Patients receiving radiation therapy to oral structures have
increases in Streptococcus mutans,Lactobacillus, and
Candida .
• Caries results from changes in the salivary glands and
saliva, including reduced flow, decreased pH, reduced
buffering capacity, increased viscosity, and altered flora.

TYPES
• Clinically, three types of radiation caries exist.
1-The most common is widespread superficial lesions
attacking buccal, occlusal, incisal, and palatal surfaces.
2-Another type involves primarily the cementum and dentin
in the cervical region. These lesions may progress around the
teeth circumferentially and result in loss of the crown.
3-A final type appears as a dark pigmentation of the entire
crown. The incisal edges may be markedly worn.
Combinations of all these lesions develop in some patients

• Radiation has a rapid effect on the salivary glands.
• In the first two weeks, with a cumulative RT dose of 20 Gy,
around 80% of salivary function is lost.
• Above 58 Gy there was a complete loss of salivary gland
function.

PREVENTION AND
MANAGEMENT
• Although radiation caries is a multifactorial condition, its
main risk factor in HNC patients is radiation treatment-
induced reduction of salivary flow.
• Exclusion of the major and minor salivary glands from the
irradiation field.
• Intensity-modulated radiotherapy (IMRT) and Three-
dimensional conformal radiation therapy (3D-CRT): techniques will
be of great benefit to patients.

• There are also artificial salivas (saliva substitutes)
capable of increasing tissue lubrication, hydration,
salivary clearance, and pH neutralization.
• Pilocarpine(pilomax)-5mg,3 times a day for 12
weeks.
• Cevimeline(Evoxac)-30mg,3 times a day for 12
weeks.

Qualitative improvement
• 1% neutral sodium fluoride gel applied daily in
custom trays could significantly reduce caries in
irradiated patients.
• combination of fluoride and chlorhexidine used
daily has been shown to offer better results for
patients with a high risk of developing radiation
caries.
• Composite and glass-ionomer fillings.

TISSUES
• TASTE BUDS
• SALIVARY GLANDS
126

OSTEORADIO NECROSIS
DEFINITION;
 An exposure of irradiated bone which fails to heal with out
intervention (Marx 1983)
 It is a chronic nonhealing wound caused by hypoxia,
hypocellularity, and hypovascularity (3H)of irradiated
tissue. Marx and Johnson (1987)
Clinical definition by Van Merkesteyn (1995)
 Bone and soft tissue necrosis of 6 months duration
excluding radiation induced periodontal breakdown

INCIDENCE
• Mandible is affected more commonly; because most oral
tumors are peri mandibular. More extensive blood supply
in maxilla
• Incidence 8.2%
• 3 fold higher in Men
• Body of mandible
• Extraction -50%
• Presurgical earlier ORN
• Combined radio and chemo

Etiology
 Radiation in excess of 50Gy- kills bone cells – osteoblasts &
fibroblasts leading to hypocellularity
 Vessels -tunica intima endarteritis, periarteritis
hyalinization and fibrosis
 Progressive obliterative arteritis.—hypovascularity
Periosteal vessels and inferior alveolar artery involved
 Hypoxia

Precipitating factors
• Triad RADIATION
TRAUMA INFECTION

Pathophysiology
Osteoradionecrosis - cumulative tissue damage
induced by radiation rather than trauma or bacterial
invasion of bone.
Complex metabolic and tissue homeostatic
deficiency seen in hypocellular, hypovascular, and
hypoxic tissue.

Effects of radiation on bone
• Depletion of osteoblasts - Increased osteoclastic
resorption of bone
Reduced bone rebuilding potential
+
• Progressive endarteritis - reduction of blood flow
through the Haversian and Volkmann’s canals
=
OSTEOPOROSIS
OSTEONECROSIS

• SPONTANEOUS ORN (39%) – degradative function exceeds new
bone production.
• TRAUMA INDUCED ORN (61%) – reparative capacity of bone
is insufficient to overcome an insult.
• Bone injury can occur through direct trauma -
1. tooth extraction [84%],
2. related cancer surgery or biopsy [12%],
3. denture irritation [1%]) or
4. by exposure of the oral cavity to the environment
secondary to overlying soft tissue necrosis.
Types of osteoradionecrosis

• By Marx(1983)
Type I – Develops shortly after radiation,
Due to synergistic effects of surgical
trauma and radiation injury.
Type II – Develops years after radiation and follows a trauma
Rarely occurs before 2 year after treatment &
commonly occurs after 6 years.
Due to progressive endarteritis and vascular effusion.
Type III
Occurs spontaneously without a preceding a traumatic event.
Usually occurs between 6 months and 3 years after radiation.
Due to immediate cellular damage and death due to radiation
treatment.
CLASSIFICATION OF
OSTEORADIONECROSIS

• Stage I – Resolved healed osteonecrosis
(A) – No pathologic fracture
(B) – Pathologic fracture
• Stage II – Chronic persistent and non-progressive osteonecrosis
• Stage III – Active progressive osteonecrosis

• Grade I, ORN confined to alveolar bone;
• Grade II, ORN limited to the alveolar bone and/or
mandible above the level of inferior alveolar canal;
• Grade III, ORN involving the mandible below the
level of inferior alveolar canal and ORN with a skin
fistula and/or pathologic fracture.

• Radiation factors
• Tumor factors
• Dental factors
• Others

CLINICAL FEATURES
• Within two years
• Asymptomatic dehiscence of mucosa
• Glabrous skin
• As necrosis progresses site more erythematous and severe, deep
burning pain
• Evidence of exposed bone
• Tissue surrounding may be ulcerated from infection or recurrent
tumor.
• Trismus
• Fetid breath
• Elevated temperature
• Exposed bone with a grey to yellow color
• Intraoral and extra oral fistula
• Pathological fracture

Signs and symptoms
• Pain
• Swelling
• Trismus
• Halitosis
• Food impaction in the area of the lesion
• Exposed bone
• Pathologic fracture
• Oro-cutaneous fistula

Radiographic changes
• Little-evident
• sequestra or involucra occur late
• radiolucent modeling -nonsclerotic

Histologically
• look like MICROANATOMIC DESERT
• Reduced vascularity, fibrosis

Management of
osteoradionecrosis
• Aim - To control infection
• Antibiotics
• Penicllin plus metronidazole or clindamycin
• Supportive therapy with fluids
• Pulsating irrigation device can be used. High pressure
should not be used debris might be forced deeply into
tissues
• Exposed bone can be mechanically debrided and
smoothed with round burs and covered with a pack
saturated with zinc peroxide and neomycin

• local irrigation (saline solution, or chlorhexidine),
systemic antibiotics in acute infectious episodes,
avoidance or irritants and oral hygiene instruction.
• Simple management refers to the gentle removal of
sequestra in sequestrating lesions
• Had 48% success rates

Treatment of
osteonecrotic wounds
• Rule out neoplastic disease
• Stabilize the patient medically especially nutritional
status
• Preoperative hyperbaric oxygen
• Debridement of necrotic mass
• Postoperative hyperbaric oxygen
• Soft tissue vascular flap support
• Bony reconstruction

Ultra sound therapy
• Is non invasive and reportedly promotes
neovascularity and neocellularity of ischemic tissues

What is HBO
• 100% oxygen in an enclosed chamber at higher-
than-atmospheric pressure where oxygen dissolves
in arterial plasma in increased amounts---up to 10
to 15 fold increase.
• Typical course consists of 30 or more treatments
done daily for six weeks.

Some Basics
• HBOT has been used in chronic wounds for about 40 years.
• 100% oxygen is delivered to a chamber under high pressure (2 to 2.4
ATA) for 90 minutes
• Typical HBOT treatment course consists of 30 or more treatments
daily.
• Administering oxygen to hypoxic tissue shown to activate fibroblast
proliferation, down-regulate inflammatory responses, cytokines, up-
regulate growth factors – all proxies for wound healing.

Clinical Hyperbaric Oxygen Therapy
Clinical
Hyperbaric
Oxygen
Therapy
Emergency Indications
•Acute Traumatic Ischemia
Crush Injuries and
Compartment Syndrome
•Carbon Monoxide Poisoning
•Gas Gangrene
•Surgical Infections
•Failed Flaps and Grafts
•Diving Injuries
Scheduled Indications
•Non-Healing Diabetic and problem
Wounds
•Radiation soft tissue necrosis, cystitis,
and proctitis.
•Osteoradionecrosis
•Osteomyelitis

Primary Mechanisms
• Hyper---oxygenation
• Vasoconstriction—reduce inflammation
• Microbiological effects
• Activate fibroblast and collagen synthesis

Secondary Mechanisms
• Angiogenesis
• Osteogenesis
• WBC Oxidative Killing
• Cell wall permeation

Side Effects of HBO
• Claustrophobia/ Confinement anxiety
• Barotrauma
• Reversible myopia

Contraindications
Absolute:
• Untreated pneumothorax
• Cis-Platin; Doxorubicin; Disulfiram
• Emphysema w/air trapping
Relative:
• Emphysema with CO2 retension
• Pulmonary lesion in CXR
• Uncontrolled high fever
• Claustrophobia
• Seizure disorder
• Malignant disease

EFFECTS IN WHOLE BODY
158
.ACUTE RADIATION SYNDROME
.HEMATOPOITIC SYNDROME
.GASTROINTESTINAL SYNDROME
.CARDIOVASCULAR SYNDROME
.CENTRAL NERVOUS SYSTEM SYNDROME

ACUTE RADIATION SYNDROME
 Acute Radiation Syndrome (ARS) is an acute illness caused
by irradiation of the entire body (or most of the body) by a
high dose of penetrating radiation in a very short period of
time (usually a matter of minutes)

stages of ARS
• Prodromal stage (N-V-D stage): The classic symptoms for this stage
are nausea, vomiting, as well as anorexia and possibly diarrhea
(depending on dose), which occur from minutes to days following
exposure. The symptoms may last (episodically) for minutes up to
several days.
• Latent stage: In this stage, the patient looks and feels generally
healthy for a few hours or even up to a few weeks.
• Manifest illness stage: In this stage the symptoms depend on the
specific syndrome and last from hours up to several months.
• Recovery or death: Most patients who do not recover will die within
several months of exposure. The recovery process lasts from several
weeks up to two years

Bone marrow (hemopoietic)
syndrome:
• (2 to7 Gy) Here severe damage may be caused to the
circulatory system.
• The bone marrow being radiosensitive, results in fall in the
number of granulocytes, platelets and erythrocytes.
• Clinically this is manifested as lymphopenia,
granulocytopenia and hemorrhage due to
thrombocytopenia and anemia due to depletion of the
erythrocytes.

Gastrointestinal syndrome
• (7 to 15 Gy): This causes extensive damage to the
gastrointestinal tract, leading to anorexia, nausea,
vomiting,severe diarrhea and malaise.

Cardiovascular and central nervous system
syndrome
• (more than 50 Gy): This produces death within one or two
days. Individuals show incordination,disorientation and
convulsions suggestive of extensive damage to the nervous
system.

REFERENCES
 1.White and pharoh-Oral Radiology-Principles and
Interpretation 6th
 2.Karjodkar Textbook of dental and maxillofacial radiology.
 3.Eric Whaites.Essentials of Dental Radiography and
Radiology.4th edition.
 4.Iannucci-Dental Radiography - Principles and Techniques,
4E.

OSTEORADIO NECROSIS
Osteoradionecrosis of jaws-Marciani RD, Ownby H E .J Oral
Maxillofac Surg 44; 218223; 1986
 Conservative management of osteoradionecrosis
J K Wong, R E Wood, Mc Lean Triple O 1997; 84:16-21
 Hyper baric oxygen in therapeutic management of
osteoradionecrosis of facial bones-S. Vudiniabola, P J
Williamson, A N Goss Int J Oral Maxillofac Surg 2000; 29:435-
438
 SALIVARY GLANDS
 Sensitivity of Salivary Glands to Radiation from Animal Models
to Therapies-J Dent Res. Oct 2009; 88(10): 894–903
 http://www.cancer.org/cancer/salivaryglandcancer/detailedgui
de/salivary-gland-cancer-treating-radiation-therapy

 MUCOSITIS
 Effect of radiotherapy on oral mucosa assessed by
quantitative exfoliative cytology.J Clin Pathol. Sep 1989;
42(9): 940–943.
 Mucositis as a biological process: a new hypothesis for the
development of chemotherapy-induced stomatotoxicity.
Oral Oncol 34 (1): 39-43, 1998. [PUBMED]
 RADIATION CARIES:
 A Review of the Biological and Clinical Aspects of Radiation
Caries-The Journal of Contemporary Dental Practice,
Volume 10, No. 4, July 1, 2009

• REFERENCES
• [1] Epstein JB, Phillips N, Parry J, Epstein MS, et al. Quality of life,
taste, olfactory and oral function following high-dose chemotherapy
and allogeneic hematopoietic cell transplantation. Bone Marrow
Transplant. 2002 Dec;30(11):785-92.
• [2] Plata-Salaman CR. Cytokines and anorexia: a brief overview.
Semin Oncol. 1998 Feb;25(1 Suppl 1):64-72.
• [3] Ripamonti C, Zecca E, Brunelli C, et al.: A randomized, controlled
clinical trial to evaluate the effects of zinc sulfate on cancer patients
with taste alterations caused by head and neck irradiation. Cancer 82
(10): 1938-45, 1998.
• [4] Overview of nutrition in cancer care: Nutrition suggestions for
symptoms relief.
http://www.cancer.gov/cancerinfo/pdq/supportivecare/nutrition/pat
ient/#Section_42 accessed 1/14/04.

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