1. RADIATION
BIOLOGY
PRESENTED BY: DR. URVASHI U. NIKTE
(PG STUDENT)
GUIDED BY: PROF. DR. MAHENDRA PATAIT
DR. KEDAR SARAF

2. INTRODUCTION:
 Radiobiology is the study of the effects of ionizing radiation on
living systems.
 The initial interaction between ionizing radiation and matter occurs
at the level of the electron within the first 10− 13 second after
exposure.
 These changes result in modification of biologic molecules within
the ensuing seconds to hours.
 In turn, the molecular changes may lead to alterations in cells and
organisms that persist for hours, decades, and possibly even
generations. These changes may result in injury or death.

3. COMPOSITION OF MATTER:
 Matter is anything that has mass and occupies space.
 It occurs in three states: Solid, Liquid and Gas
 ATOM is the fundamental unit of matter

5. The number of protons only in a nucleus is called the atomic
number ( the Z number).
The atomic mass (A) is the total number of protons and
neutrons in the nucleus of an atom.
When the number of protons equals the number of electrons
that atom is known to be in a stable or neutral state
The electrons in the orbit are maintained by the electrostatic
force between the positively charged nucleus and the
negatively charged electrons on the one hand, balanced by the
centrifugal force of the revolving electrons.

6. ELECTROSTATIC FORCE:
It is the force of attraction between protons and electrons.

7. CENTRIFUGAL FORCE:
It is the force that pulls electrons away from the nucleus.

8. EF
CF
Balance between ELECTROSTATIC and CENTRIFUGAL forces
keeps the electrons in orbit around the nucleus.

9. IONIZATION:
 When the number of orbiting electrons in an atom is equal to
the number of protons in its nucleus, the atom is electrically
neutral.
If an electrically neutral atom loses an electron, it becomes a
positive ion and the free electron is a negative ion. This process of
forming an ion pair is termed ionization.

11.  Radiation is the transmission of energy through space and
matter.
 Based on the interaction with the matter there are two
types of radiation
1. Ionizing radiation
2. Non- ionizing radiation

13. 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
PARTICULATE
ELECTROMAGNETIC

14. PARTICULATE/CORPUSCULAR RADIATION
Particulate radiation consists of atomic nuclei or subatomic
particles moving at high velocity.
e.g. alpha particles, beta particles, and cathode rays are
examples of particulate radiation.

15. The capacity of particulate radiation to ionize atoms
depends on its mass, velocity, and charge. The rate of
loss of energy from a particle as it moves along its track
through matter (tissue) is its linear energy transfer (LET) .
A particle loses kinetic energy each time it ionizes adjacent matter; the
greater its physical size and charge and the lower its velocity, the greater is
its LET.
For example, alpha particles, with their high charge and low velocity,
lose kinetic energy rapidly and have short path lengths (are densely
ionizing); thus they have a high LET. Beta particles are much less densely
ionizing because of their lighter mass and lower charge and thus have a
lower LET. They penetrate through tissue more readily than
do alpha particles.

18. According to wavelengths radiation can differ in
properties:
Short wavelength
OR
Long wavelength

19. The short wavelength Increased frequency
increased energy accompanied with it increase the
power of penetration. They are termed as Hard Radiation which
is characterised by low absorption and low ionisation potential.
The long wavelength decreased frequency
decreased energy accompanied with it
less power of penetration. They are termed as Soft Radiation
which is characterised by high absorption and high ionisation
potential.

20. ELECTROMAGNETIC RADIATION:
Electromagnetic radiation is the movement of energy
through space as a combination of electric and magnetic fields.
It is generated when the velocity of an electrically charged
particle is altered.
E.g. Gamma rays, x rays, ultraviolet rays, visible light, infrared
radiation(heat), microwaves, and radio waves.

22. INTERACTIONS OF XRAYS WITH MATTER:
 The intensity of an x-ray beam is reduced by interaction with the
matter it encounters. This attenuation results from interactions of
individual photons in the beam with atoms in the absorber.
 The x-ray photons are either absorbed or scattered out of the beam.
 In a dental x-ray beam there are three means of beam attenuation:
(1) COHERENT SCATTERING
(2) PHOTOELECTRIC ABSORPTION
(3) COMPTON SCATTERING

24. 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.

25. 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.

26. 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).

27. 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)

28. 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.

32. Ionizing radiation absorbed by human tissue has enough
energy to remove electrons from the atoms that make up
molecules of the tissue.
When the electron that was shared by the two atoms to form a
molecular bond is dislodged by ionizing radiation, the bond is
broken and thus, the molecule falls apart. This is a basic model
for understanding radiation damage.

33. Radiation Causes Ionizations of:
Cells which may affect
MOLECULES
which may affect
TISSUES
which may affect
ORGANS
which may affect
THE WHOLE BODY

34. Why are we concerned about Radiation?
Ionizing Radiation
Human Cells
Atoms in Cells Form Ions
Change in Cell Cell DiesNo Change in Cell
Not Replaced
ReplacedReproduces
Malignant Growth Benign Growth

35. 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.

36. 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.

37. • 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).

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

39. LINEAR ENERGY TRANSFER (LET)
 Amount of energy is transferred from
ionizing radiation to soft tissue
39

40. RELATIVE BIOLOGIC
EFFECTIVENESS(RBE)
Biologic response compared with
two types of radiation
40

41. LATENT PERIOD
• The time lapse between exposure of the radiation and the
appearance of the effects.
41

42. 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.

43. 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.)

44. • 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.

45. MEDIAN LETHAL DOSE
 The amount of ionizing radiation that will kill 50
percent of a population in a specified time
Abbreviation: LD50

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

47. 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

49. RADIATION CHEMISTRY
• Radiation acts on living systems through direct and indirect
effects.
• When the energy of a photon or secondary electron ionizes
biologic macromolecules, the effect is termed direct.
• Alternatively, a photon may be absorbed by water in an
organism, ionizing some of its water molecules. The resulting
ions form free radicals (radiolysis of water) that in turn interact
with and produce changes in biologic molecules. Because
intermediate changes involving water molecules are required to
alter the biologic molecules, this series of events is termed
indirect.

50. DIRECT EFFECT:
• In direct effects, biologic molecules (RH, where R is the
molecule and H is a hydrogen atom) absorb energy from
ionizing radiation and form unstable free radicals (atoms
or molecules having an unpaired electron in the valence
shell).
• Generation of free radicals occurs in less than 10− 10
second after interaction with a photon. Free radicals are
extremely reactive and have very short lives, quickly
reforming into stable configurations by dissociation
(breaking apart) or cross-linking (joining of two
molecules). Free radicals play a dominant role in
producing molecular changes in biologic molecules.

51. Free radical production:
 RH + X-radiation R* + H+ + e-
Free radical fates:
• R* X + Y*DISSOCIATION
• R* + S* RSCROSS- LINKING

52. Because the altered biologic molecules differ structurally
and functionally from the original molecules, the
consequence is a biologic change in the irradiated
organism. Approximately one third of the biologic effects
of x-ray exposure result from direct effects. However,
direct effects are the most common outcome for
particulate radiation such as neutrons and α particles.

54. RADIOLYSIS OF WATER
• Because water is the predominant molecule in biologic
systems (about 70% by weight), it frequently participates in
the interactions between x-ray photons and biologic
molecules. A complex series of chemical changes occurs in
water after exposure to ionizing radiation. Collectively these
reactions result in the radiolysis of water.
• photon + H2O H* + OH*

55. H2O
HOH+
e-
water
electron
Positively charged
water molecule
Radiation reacts with water to produce an electron and a positively
charged water molecule.

56. H2O
HOH+
e- + H2O HOH-
water
negatively charged
water molecule
electron water
Positively charged
water molecule
The electron reacts with another water molecule to produce a
negatively charged water molecule

57. H2O
HOH+
H+
OH*
e- + H2O HOH-
water
negatively charged
water molecule
Hydrogen
ion
Hydroxyl
radical
electron
water
Positively charged
water molecule
The positively charged water molecule dissociates into a hydrogen ion and
a hydroxyl radical.

58. H2O
HOH+
H+
OH*
H* OH-
e- + H2O HOH-
water
negatively charged
water molecule
Hydrogen
ion
Hydroxyl
radical
electron water
Positively charged
water molecule
hydrogen
radical
Hydroxyl
ion
The negatively charged
water molecule dissociates
into a hydrogen radical and a
hydroxyl ion.

59. Reactions
 The previous reactions produce free electrons (e-),
the ions H- and OH-, the free radicals H* and OH*.
 The fate of these products are…….

60. H2O
HOH+
H+
OH*
H* OH-
e- + H2O HOH-
HOH+ + e- H2O
The positively charged water
molecule and the electron
recombine to form water.

61. H2O
HOH+
H+
OH*
H* OH-
e- + H2O HOH-
H+ + OH- H2O
The ions combine to form water.

62. H2O
HOH+
H+
OH*
H* OH-
e- + H2O HOH-
H* + OH* H2O
The radicals combine to form
water.

63. H2O
HOH+
H+
OH*
H* OH-
e- + H2O HOH-
OH*
OH* + OH* H2O2
The hydroxyl radical reacts with
another hydroxyl radical to form
hydrogen peroxide.

64. Free Radicals
 A free radical is an atom or
molecule that has an
unpaired electron in its
valence shell.
 These free radicals are non-
selective when pairing up
with electrons from other
atoms, including those that
make up the DNA molecule.

65. INDIRECT EFFECTS:
• Indirect effects are those in which hydrogen and hydroxyl free
radicals, produced by the action of radiation on water, interact
with organic molecules. The interaction of hydrogen and
hydroxyl free radicals with organic molecules results in the
formation of organic free radicals. About two thirds of
radiation-induced biologic damage results from indirect effects.
Such reactions may involve the removal of hydrogen:
RH + OH* R* + H2O
RH + H* R* + H2

66. The OH* free radical is more important in causing such damage.
Organic free radicals are unstable and transform into stable, altered
molecules.
These altered molecules have different chemical and biologic
properties from the original molecules.

69. CHANGES IN DEOXYRIBONUCLEIC
ACID (DNA)

72. DETERMINISTIC &
STOCHASTIC EFFECTS
• Radiation injury to organisms results from either the
killing of large numbers of cells (deterministic effects)
or sub lethal damage to individual cells that results in
cancer formation or heritable mutation (stochastic
effects).

73. DETERMINISTIC EFFECTS STOCHASTIC EFFECTS
EXAMPLES • Mucositis resulting from radiation
therapy to oral cavity.
• Radiation induced cataract
formation.
• Radiation induced cancer.
• Heritable effects.
CAUSED BY Killing of many cells Sublethal damage to DNA
THRESHOLD DOSE Yes: sufficient cell killing required to
cause a clinical response
No: even one photon could cause a
change in DNA that leads to a cancer
or a heritable effect.
SEVERITY OF CLINICAL EFFECTS AND
DOSE
Severity of clinical effects is
proportional to dose. The greater the
dose the greater the effect.
Severity of clinical effects is
independent of dose.
All-or-none response; an individual
either has effect or does not.
PROBABILITY OF HAVING EFFECT AND
DOSE
Probability of effect independent of
dose. All individuals show effect when
dose is above threshold.
Frequency of effect proportional to
dose. The greater the dose the greater
the chance of having the effect.
COMPARISON OF DETERMINISTIC AND
STOCHASTIC EFFECTS OF RADIATION

74. DETERMINISTIC
EFFECTS ON CELLS

75. EFFECTS ON INTRACELLULAR
STRUCTURES
• The effects of radiation on intracellular structures result
from radiation-induced changes in their macromolecules.
• Although the initial molecular changes are produced within
a fraction of a second after exposure, cellular changes
resulting from moderate exposure require a minimum of
hours to become apparent.
• These changes are manifest initially as structural and
functional changes in cellular organelles. The changes may
cause cell death.

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

77. NUCLEUS
• A wide variety of radiobiologic data indicate that the nucleus is more radiosensitive (in
terms of lethality) than the cytoplasm, especially in dividing cells.
• Nucleus is more radio sensitive than the cytoplasm since it contains the DNA.

78. PROTEINS
 Denaturation.
 Primary structure of the protein is usually not significantly altered
 Secondary and tertiary structures are effected by breakage of
hydrogen or disulfide bonds
 Inactivation of enzymes sometimes occurs.

79. MITOCHONDRIA
Mitochondria demonstrate –
• Increased permeability
• Swelling
• Disorganization of the internal cristae

80. 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

81. • Chromosome aberrations have been detected in peripheral
blood lymphocytes of patients exposed to medical diagnostic
procedures.
• Moreover, 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.
• The frequency of aberrations is generally proportional to the
radiation dose received.

82. EXAMPLES OF MUTATIONS

84. EFFECTS ON CELL REPLICATION
• Radiation is especially damaging to rapidly dividing cell systems, such
as skin and intestinal mucosa and hematopoietic tissues.
• Irradiation of such cell populations will cause a reduction in size of
the irradiated tissue as a result of mitotic delay (inhibition of
progression of the cells through the cell cycle) and cell death (usually
during mitosis).
• 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, and apoptosis.

85. • DNA DAMAGE
• BYSTANDER EFFECT
Cells that are damaged by radiation release into their immediate
environment molecules that kill nearby cells. This bystander effect
has been demonstrated for both α particles and x rays and causes
chromosome aberrations, cell killing, gene mutations, and
carcinogenesis.

86. When a cell is damaged by radiation, it can send signals to bystander cells,
which are the cells near the “hit” cell.
The signals sent by the damaged cell may disrupt the normal function of it’s
neighboring cells, or it may stimulate them to respond with additional signals
back to the damaged cell or to other nearby cells.
The signals sent by the bystander cells may help repair the damaged cell, or it
may trigger the cell to commit cell suicide.

87. • DELAYED 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.

88. • APOPTOSIS
Apoptosis, also known as programmed cell death, occurs during normal
embryogenesis. Cells round up, draw away from their neighbours, and condense
nuclear chromatin. This characteristic pattern, different from necrosis, can be
induced by radiation in both normal tissue and in some tumours. Apoptosis is
particularly common in haemopoietin and lymphoid tissues.

89. DETERMINISTIC EFFECTS
ON TISSUES AND
ORGANS

90. 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.

91. 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.

92. 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 osteoradionecrosis.
• 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 counter
arguments.

94. Relative Radiosensitivity of Various Cells

95. Relative Radiosensitivity of Various
Organs

96. SHORT TERM EFFECTS
• The short-term effects of radiation on a tissue (effects seen in the first days or
weeks after exposure) are determined primarily by the sensitivity of its
parenchymal cells. When continuously proliferating tissues (e.g., bone
marrow, oral mucous membranes) are irradiated with a moderate dose, cells
are lost primarily by reproductive death, bystander effect, and apoptosis.
• The extent of cell loss depends on damage to the stem cell pools and the
proliferative rate of the cell population. The effects of irradiation on such
tissues become apparent quickly as a reduction in the number of mature cells
in the series.
• Tissues composed of cells that rarely or never divide (e.g., neurons or muscle)
demonstrate little or no radiation-induced hypoplasia over the short term.

97. LONG TERM EFFECTS
• The long-term deterministic effects of radiation on tissues and organs (seen
months and years after exposure) are a loss of parenchymal cells and
replacement with fibrous connective tissue. These changes are caused by
reproductive death of replicating cells and by damage to the fine
vasculature.
• Damage to capillaries leads to narrowing and eventual obliteration of
vascular lumens. This impairs the transport of oxygen, nutrients, and waste
products and results in death of all cell types dependent on this vascular
supply.
• Thus both dividing (radiosensitive) and non dividing (radioresistant)
parenchymal cells are replaced by fibrous connective tissue, a progressive
fibroatrophy of the irradiated tissue.

98. MODIFYING FACTORS
 DOSE
 DOSE RATE
 OXYGEN
 LINEAR ENERGY TRANSFER

99. RADIOTHERAPY IN THE
ORAL CAVITY

100. RATIONALE
• The oral cavity is irradiated during radiation therapy of
radiosensitive oral malignant tumors, usually squamous cell
carcinomas.
• Radiation therapy for malignant lesions in the oral cavity is usually
indicated when the lesion is radiosensitive, advanced, or deeply
invasive and cannot be approached surgically.
• Combined surgical and radiotherapeutic treatment often provides
optimal treatment. Increasingly, chemotherapy is being combined
with radiation therapy and surgery.

101. • Fractionation of the total x-ray dose into multiple small doses provides
greater tumor destruction than is possible with a large single dose.
• Fractionation characteristically also allows increased cellular repair of
normal tissues, which are believed to have an inherently greater capacity
for recovery than tumor cells.
• Fractionation also increases the mean oxygen tension in an irradiated
tumor, rendering the tumor cells more radiosensitive. This results from
killing rapidly dividing tumor cells and shrinking the tumor mass after the
first few fractions, reducing the distance that oxygen must diffuse from the
fine vasculature through the tumor to reach the remaining viable tumor
cells.
• The fractionation schedules currently in use have been established
empirically.

102. RADIATION EFFECT ON
ORAL TISSUES

103. • Typically 2 G y is delivered daily, bilaterally through 8- cm × 10-cm
fields over the oropharynx, for a weekly exposure of 10 Gy. This
continues typically for 6 to 7 weeks until a total of 64 to 70 Gy is
administered.
• Cobalt is often the source of γ radiation; however, on occasion
small implants containing radon or iodine 125 are placed directly in
a tumor mass. Such implants deliver a high dose of radiation to a
relatively small volume of tissue in a short time.
• Recently a three dimensional technique called intensity-modulated
radiotherapy (IMRT) has been used to control the dose distribution
with high accuracy.

104. 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

105. • The oral mucous membrane contains a basal layer composed of rapidly
dividing, radiosensitive stem cells.
• Near the end of the second week of therapy, as some of these cells die,
the mucous membranes begin to show areas of redness and inflammation
(mucositis).
• As the therapy continues, the irradiated mucous membrane begins to
separate from the underlying connective tissue, with the formation of a
white to yellow pseudomembrane (the desquamated epithelial layer).
• At the end of therapy the mucositis is usually most severe, discomfort is at
a maximum, and food intake is difficult. Good oral hygiene minimizes
infection.
• Topical anesthetics may be required at mealtimes.
• Secondary yeast infection by Candida albicans is a common complication
and may require treatment.
MUCOSITIS

106. • After irradiation is completed, the mucosa begins to heal rapidly.
Healing is usually complete by about 2 months. Later the mucous
membrane tends to become atrophic, thin, and relatively avascular.
• This long-term atrophy results from progressive obliteration of the fi
ne vasculature and fibrosis of the underlying connective tissue.
These atrophic changes complicate denture wearing because they
may cause oral ulcerations of the compromised tissue.
• Ulcers may also result from radiation necrosis or tumor recurrence.
A biopsy may be required to make the differentiation.

109. 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.

110. • Topical anesthetics:
– Lidocaine: viscous, ointments, Sprays.
– Benzocaine: sprays, gels.
– 0.5% or 1.0% dyclonine hydrochloride (HCl).
– Diphenhydramine solution.
• Mucosal coating agents:
– 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.

111. TASTE BUDS

112. • Taste buds are sensitive to radiation. Doses in the therapeutic range cause
extensive degeneration of the normal histologic architecture of taste buds.
• Patients often notice a loss of taste acuity during the second or third week
of radiotherapy. Bitter and acid flavors are more severely affected when
the posterior two thirds of the tongue is irradiated and salt and sweet
when the anterior third of the tongue is irradiated.
• Taste acuity usually decreases by a factor of 1000 to 10,000 during the
course of radiotherapy. Alterations in the saliva may partly account for this
reduction, which may proceed to a state of virtual insensitivity.
• Taste loss is reversible and recovery takes 60 to 120 days.

113. 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.

114. • 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 radiotherapy 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.

115. • 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.

116. • The major salivary glands are at times unavoidably exposed to 20 to 30 Gy
during radiotherapy for cancer in the oral cavity or oropharynx.
• The parenchymal component of the salivary glands is rather radiosensitive
(parotid glands more so than submandibular or sublingual glands).
• A marked and progressive loss of salivary secretion (hyposalivation) is
usually seen in the first few weeks after initiation of radiotherapy. The
extent of reduced flow is dose dependent and reaches essentially zero at
60 Gy.
• The mouth becomes dry (xerostomia) and tender, and swallowing is
difficult and painful. Patients with irradiation of both parotid glands are
more likely to complain of dry mouth and difficulty with chewing and
swallowing than are those with unilateral irradiation.
SALIVARY GLANDS

117. • The mouth becomes dry (xerostomia) and tender, and swallowing is
difficult and painful. Patients with irradiation of both parotid glands are
more likely to complain of dry mouth and difficulty with chewing and
swallowing than are those with unilateral irradiation.
• Various saliva substitutes are available to help restore function.
• Use of IMRT has helped to spare the contralateral salivary glands and thus
minimize the loss of salivary function.

118. TEETH
• 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.
Such exposure may retard or abort root formation, but the eruptive
mechanism of teeth is relatively radiation resistant.
• Irradiated teeth with altered root formation still erupt. In general, the
severity of the damage is dose dependent.

119. • Adult teeth are resistant to the direct effects of radiation
exposure.
• Pulpal tissue demonstrates long-term fibroatrophy after
irradiation.
• Radiation has no discernible effect on the crystalline structure
of enamel, dentin, or cementum, and radiation does not
increase their solubility.

120. RADIATION CARIES
• 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.
• After radiotherapy that includes the major salivary glands, the microflora
undergo a pronounced change, rendering them acidogenic in the saliva and
plaque.
• 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.
• The residual saliva in individuals with xerostomia also has a low concentration of
Ca+2 ions.

121. 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.

122. MANAGEMENT

123. • 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.
• 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.

124. BONE
• Treatment of cancers in the oral region often includes irradiation of the
mandible or maxilla.
• The primary damage to mature bone results from radiation-induced
damage to the vasculature of the periosteum and cortical bone, which are
normally already sparse.
• Radiation also acts by destroying osteoblasts and, to a lesser extent,
osteoclasts. Subsequent to irradiation, normal marrow may be replaced
with fatty marrow and fibrous connective tissue.
• The marrow tissue becomes hypovascular, hypoxic, and hypocellular.

125. • In addition, the endosteum becomes atrophic, showing
a lack of osteoblastic and osteoclastic activity, and
some lacunae of the compact bone are empty, an
indication of necrosis.
• The degree of mineralization may be reduced, leading
to brittleness, or little altered from normal bone. When
these changes are so severe that bone death results
and the bone is exposed, the condition is termed
osteoradionecrosis.

126. OSTEORADIONECROSIS
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

127. • Osteoradionecrosis (ORN), also known as post
radiation osteonecrosis (PRON).
• It was first described by Regaud 1920.
• A serious, debilitating and deforming potential
complication of radiation therapy

128. 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

129. 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

130. • Meyer in 1970 –
Triad of radiation, trauma, and infection
- development of osteoradionecrosis.
• Irradiated bone +
Traumatic event +
Ingress of microorganisms =
Osteoradionecrosis
PATHOPHYSIOLOGY OF
OSTEORADIONECROSIS

132. • Radiation damaged cells not replaced by cells of the
same type
• Results in less cellular, more extracellular elements –
collagen.
• Fibrotic and poorly vascularized tissue – absent
healing ability.
• Breakdown – absent cellular turnover
Spontaneous breakdown.
Three "H" principle

133. CLASSIFICATION 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.

134. SIGNS AND SYMPTOMS
 Pain
 Swelling
 Trismus
 Halitosis
 Food impaction in the area of the lesion
 Exposed bone
 Pathologic fracture
 Oro-cutaneous fistula

135. CLINICAL PRESENTATION

136. RADIOGRAPHIC
PRESENTATION

137. Management of
osteoradionecrosis
• Aim - To control infection
• Antibiotics
• Penicillin 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

138. • 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

139. 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

140. Hyperbaric oxygen therapy
• HBO is an adjuvant to surgery rather than an independent
therapy.
• It was first recommended by Valenzuela (1887) as a treatment
for bacterial infections.
• Reports of the benefits of HBO in osteoradionecrosis were
first reported in the 1970’s by Mainous, Hart and Boyne.

141. Hyperbaric oxygen therapy
• The basic mechanism of hyperbaric oxygen therapy is
endothelial cell proliferation resulting in neovascularisation and
collagen synthesis.
• It consists of exposing a patient to intermittent short term 100%
oxygen inhalation at a pressure greater than 1 atmosphere.

142. Hyperbaric oxygen therapy
• Marx (1983) presented a new concept in osteoradionecrosis
management - Marx HBO / surgical protocol.
• The compromised bone and soft tissues are improved and
revascularised with HBO and then if necessary, the necrotic
bone is surgically removed.
• The patient’s response or lack of response to HBO is the main
indicator for surgery.
• The primary thrust is to distinguish dead bone from merely
compromised bone and to surgically resect all dead bone.

143. Stage I
• Perform 30 HBO dives (1 dive per day, Monday-Friday) to 2.4
atmospheres for 90 minutes in a multiplace chamber or 2.0
ATA for 120 min in a monoplace chamber .
• Reassess the patient to evaluate decreased bone exposure,
granulation tissue covering exposed bone, resorption of
nonviable bone, and absence of inflammation.
• For patients who respond favorably, continue treatment to a
total of 40 dives.
• For patients who are not responsive, advance to stage II.

144. Stage 2
• Perform transoral sequestrectomy with primary wound
closure followed by continued HBO to a total of 40 dives.
• If wound dehiscence occurs, advance patients to stage III.

145. Stage 3
• Patients who present with orocutaneous fistula,
pathologic fracture, or resorption to the inferior
border of the mandible advance to stage III
immediately after the initial 30 dives.
• Perform transcutaneous mandibular resection, wound closure,
and mandibular fixation with an external fixator or
maxillomandibular fixation, followed by an additional 10
postoperative HBO dives.

146. Stage 3 R
• Perform mandibular reconstruction 10 weeks after
successful resolution of mandibular ORN.
• Reconstruction of the mandible in these patients consisted
of either autogenous particulate bone and marrow within a
custom-made stainless steel metal crib or autogenous
particulate bone and marrow within a freeze-dried
allogenic bone framework .
• Complete 10 additional postoperative HBO dives.

147. • With adherence to this protocol, Marx noted resolution of all
cases of osteoradionecrosis within one of the stages.
• More specifically, 15% resolved in stage I, 15% resolved
during stage II, and the remainder (70%) resolved in stage III.
Results

149. Contraindications for HBO therapy
1. Untreated pneumothorax - (Absolute
contraindication)
2. Pregnancy
3. Emphysema
4. Upper respiratory tract infection
5. Uncontrollable fever
6. Optic neuritis
7. Ear problems

150. Prevention of osteoradionecrosis
• Prior to radiation therapy- Dental consultation - To
achieve optimal oral health.
• Sleeper (1950) and Meyer (1958) - recommendations
before irradiation is started.
1. The mouth should be made as clean as possible by
scaling and irrigation.
2. All infections of soft tissues should be eliminated.
3. All infected and non-vital teeth should be extracted. All
teeth in the line of irradiation, good or bad, also
should be extracted.

151. Prevention of osteoradionecrosis
4. All teeth periodontally involved should be extracted.
5. If the parotid and submandibular glands are to receive
heavy irradiation, all teeth should be extracted.
6. If the mouth shows much neglect throughout, all teeth
should be extracted.
7. The use of antibiotic prophylaxis b4 extraction, though
common practise, has not been validated in any study.
However, prophylaxis could be incorporated into the
protocol if desired.

152. Prevention of osteoradionecrosis
8. The patient should be thoroughly instructed in the
maintenance of absolute hygienic care of the mouth.
9. Fluoride therapy should be used to prevent irradiation
caries of any remaining teeth.
10. No radiotherapy should be attempted for 7-10 days
following extractions in the mandible or for 3-6 days in the
maxilla. If possible the radiation should start only 21 days
after the tooth extractions.

153. 1. Strict oral hygiene.
2. If future work on the teeth or an operation - patients
must inform the physician or dentist that their jaws
have been previously irradiated.
3. Preferably no further extractions. If a tooth in the area
of irradiation becomes caries - extraction must be
done as atraumatically as possible under a course of
antibiotics both preoperatively and postoperatively.
4. Dentures should not be used in the irradiated arch for
one year after therapy.

154. MUSCULATURE
• Radiation may causes inflammation and fibrosis resulting
in contracture and trismus in the muscles of mastication.
• Usually the masseter or pterygoid muscles are involved.
Restriction in mouth opening usually starts about 2
months after radiotherapy is completed and progresses
thereafter.
• An exercise program may be helpful in increasing opening
distance.

156. DETERMINISTIC EFFECTS OF
WHOLE BODY RADIATION

157. ACUTE RADIATION
SYNDROME
• The acute radiation syndrome is a collection of signs and
symptoms experienced by persons after acute whole-body
exposure to radiation.
• Information about this syndrome comes from animal
experiments and human exposures in the course of medical
radiotherapy, atom bomb blasts, and radiation accidents.
• Individually, the clinical symptoms are not unique to
radiation exposure, but taken as a whole, the pattern
constitutes a distinct entity

158. 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

159. • HEAMATOPOIETIC SYNDROME- Whole body exposure- 2-7 Gy.
High mitotic activity.
Highly radiosensitive.
Clinical signs include infection,
hemorrhage and anemia.
• GASTROINTESTINAL SYNDROME- Whole body exposure- 7-15 Gy.
Injury to basal epithelial cells of
the intestinal villi.
Clinical signs include diarrhoea,
dehydration and loss of weight.
• CVS AND CNS SYNDROME- Whole body exposure- excess of 50 Gy.
Usually cause death in 1 to 2 days.
CVS shows collapse of circulatory system with a
precipitous fall in blood pressure.
Victims also may show intermittent stupor,
incoordination, disorientation, and convulsions
suggestive of extensive damage to the nervous
system.

160. MANAGEMENT OF ACUTE
RADIATION SYNDROME
• The presenting clinical problems govern the management of
different forms of acute radiation syndrome.
• Antibiotics are indicated when the granulocyte count falls.
• Fluid and electrolyte replacement is used as necessary.
• Whole blood transfusions are used to treat anemia, and
platelets may be administered to arrest thrombocytopenia.
• Bone marrow grafts are indicated between identical twins
because there is no risk for graft-versus-host disease.

161. 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.

162. • LATE EFFECTS:
A number of late deterministic effects have been found in the survivors of the atomic bombing
of Hiroshima and Nagasaki.
 Growth And Development
Children exposed in the bombings showed impairment of growth and development. They have
reduced height, weight, and skeletal development. The younger the individual was at the time
of exposure, the more pronounced the effects.
 Cataracts
The threshold for induction of cataracts (opacities in the lens of the eye) ranges from about 0.6
G y when the dose is received in a single exposure to 5 Gy when the dose is received in multiple
exposures over a period of weeks. These doses are much larger than those from dental
radiography. Most affected individuals are unaware of their presence.
 Life Span Shortening
The survivors of the atomic bombings show a clear decrease in median life expectancy with
increasing radiation dose. The reduction ranges from 2 months up to 2.6 years by dose group,
with an overall mean of 4 months. Survivors demonstrate increased frequency of heart disease,
stroke, and diseases of the digestive, respiratory, and hematopoietic systems.

163. STOCHASTIC
EFFECTS

164. • Stochastic effects result from sublethal changes in the
DNA of individual cells.
• The most important consequence of such damage is
carcinogenesis.
• Heritable effects, although much less likely, can also
occur.

165. CARCINOGENESIS
DNA RADIATION
RADIATION INDUCED GENE MUTATION
PROTO-ONCOGENES TO
ONCOGENES
LOSS OF FUNCTION OF TUMOR
SUPPRESSOR GENES

167. Basic Principles of
Radiation Genetics
• Radiation causes increased frequency of spontaneous
mutations rather than inducing new mutations.
• The frequency of mutations increases in direct proportion to
the dose, even at very low doses, with no evidence of a
threshold.
• The majority of mutations are deleterious to the organism.
• Dose rate is important. At low dose rates the frequency of
induced mutations is greatly reduced.
• Males are much more radiosensitive than females.
• The rate of mutations is reduced as the time between
exposure and conception increases.

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172. Thank You