Radiation Biology

Presented By:
Aarya.H.Nair

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 CONTENTS
• Introduction
• Effects in atoms & molecules
• Chemical effects of radiation
• Biologic effects of radiation
• Determinants of radiation injury
• Radiation effects on the Oral cavity
• Syndromes
• Conclusion

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 INTRODUCTION
• Radiation is the emission or transmission of
energy in the form of waves / particles through
space or through a material medium
– Electromagnetic radiation
– Particulate radiation
– Acoustic radiation

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 PIONEERS IN THE FIELD OF RADIOLOGY

SIR EMIL GRUBBE-first

documented response to radiation SIR ANTOINE HENRI
SIR WILHELM CONRAD BECQUEREL-
RONTGEN-discovered X-rays discovered radioactivity

MADAM MARIE
CURIE-discovered
radioactivity
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 HISTORY OF RADIATION DISASTERS

HIROSHIMA-
NAGASAKI-1945 MAYAK NUCLEAR
PLANT-1957

FUKUSHIMA
DISASTER,2011

CHERNOBYL SOVIET SUBMARINE

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DISASTER,1986 ACCIDENT-1985
Radiation biology is a portion of science that
studies the effects of ionizing radiations on
living tissues

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• The initial interaction between ionizing radiation &
matter occurs at the level of the electron within the
first 10 to the power of -13 sec.

• These changes result in modification of biological

molecules within seconds to hours

• Alterations in cells & organisms can persist for

hours,decades & even generations,which may result
in injury/death of the cell / organism
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EFFECTS IN ATOMS & MOLECULES
EXCITATION

RADIATION MOLECULAR
CHANGE

IONIZATION

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 EXCITATION
INTERACTION OF X-RAY
WITH ATOM’S ORBITAL MOMENTARY VIBRATION
ELECTRON

CHANGES IN THE FORCE

HOLDING THE ATOMS

RELEASE OF ENERGY OF
VIBRATION
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 IONIZATION

•Unstable
•Highly reactive
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 FREE RADICAL FORMATION
• Ionization of water

• A free radical is an uncharged atom / molecule that

exists with a single, unpaired electron in its outermost
shell
• Highly reactive & unstable
• To achieve stability:
– Recombine without causing changes in the molecule
– Combine with other free radicals & causes changes
– Combine with ordinary molecules to form a toxin[H2O2]

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BREAKING OF MOLECULAR BONDS
• The ionized atom may cause breakage of the
molecule into 2/more pieces
• Loss of cell function
• Disruption of intracellular organelles
• Death of the cell

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 CHEMICAL EFFECTS OF RADIATION
• DIRECT EFFECT:
– Direct alteration of biologic molecules forming
unstable free radicals
– Free radical production:
• RH + X-radiation R + H ion + e-
– Free radical fates:
• Dissociation: R X+Y
• Cross-linking: R+S RS
– Altered molecule is structurally & functionally
different
– Accounts for 1/3rd of the biologic effects 13
• INDIRECT EFFECT:
– Accounts for 2/3rd of biological damage
– X-ray interaction with water
• RH + OH R + H2O
• RH + H R+H2

• OH free radical more important in causing damage

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 Biologic effects
• NUCLEIC ACIDS
– Damage to DNA : carries the genetic information
necessary for cell replication & regulation of all
cellular activity
– Different types of alterations in DNA:
• Change / loss of a base
• Disruption of hydrogen bonds between DNA strands
• Breakage of 1/more strands
• Cross linking of DNA strands within the helix

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• PROTEINS:
– Changes in their secondary & tertiary structures

DENATURATION
– Primary structure unaltered
– Induce intermolecular & intramolecular cross-
linking
– Dose required to induce denaturation is much
higher than that required to induce gross cellular
changes/cell death
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 At cellular level

– EFFECTS ON INTRACELLULAR
STRUCTURES:
• Nucleus: Radiosensitive DNA

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• Chromosome aberrations:
– Useful markers for radiation injury
– Type of damage: depends on the stage of the cell in the cell
cycle at the time of irradiation

Cell cycle

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• Chromatid aberrations • Chromosome aberrations

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• CYTOPLASM:
– Large doses of radiation (30-50Gy)
• Mitochondria demonstrates increased permeability, swelling &
disorganization of the internal cristae

– Minor role in the cellular changes seen in rapidly dividing

cells after exposure to moderate doses of radiation(2-4 Gy)

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EFFECTS ON CELL KINETICS

• LOW DOSE: Mild mitotic delay

in G2 cells
• MODERATE DOSES: Longer
MITOTIC mitotic delay (G2 block) & some
DELAY cell death
• LARGE DOSES: Profound
mitotic delay with incomplete
recovery

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 CELL DEATH:

Caused by
Chromosome
damage to Cell death
aberrations
the nucleus

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• BYSTANDER EFFECT:
– Damaged by radiation release into their immediate
environment molecules that kill nearby cells
– Alpha & x –rays
– Chromosome aberrations,cell killing,gene mutations &
carcinogenesis
• APOPTOSIS:
– Programmed cell death
– During normal embryogenesis
– Cells round up, draw away from their neighbours &
condense nuclear chromatin
– Common in hemopoietic & lymphoid tissues

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 • Involves enzymatic repair of
RECOVERY: single-strand breaks of DNA
• Higher total dose is required

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 TYPES OF BIOLOGIC EFFECT

• STOCHASTIC EFFECT:
– That effect for which the probability of the
occurrence of a change,rather than its severity is
dose-dependent
– No threshold
– Eg: Radiation induced Ca

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• DETERMINISTIC EFFECT
– Severity of the response is proportional to the dose
– Dose threshold below which the response is not
seen
– Eg: Oral changes after RT

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 RADIOSENSITIVITY & CELL TYPE
• The most radiosensitive cells are:
– High mitotic rate
– Undergo many future mitoses
– Most primitive in differentiation

• Exception: lymphocytes & oocytes

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• 5 categories of radiosensitive cells:
1. VEGETATIVE INTERMITOTIC CELLS: Early
precursor cells, Basal cells of OMM
2. DIFFERENTIATING INTERMITOTIC CELLS:
Dividing & replicating cells of IEE, Oocytes, Spermatocytes
3. CONNECTIVE CELLS: Vascular endothelial cells,
Fibroblasts, Mesenchymal cells
4. REVERTING POST-MITOTIC CELLS: Acinar cells,
ductal cells of salivary gland,Pancreas
5. FIXED POST-MITOTIC CELLS: Neurons, Striated
muscle cells, Squamous epithelial cells

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 RADIATION EFFECTS AT THE
TISSUE & ORGAN LEVEL
• Measured by its response to irradiation
• Severity depends on the dose & thus the amount
of cell loss
• SHORT TERM EFFECTS:
– Determined by its sensitivity of its parenchymal cells
– Continuously proliferating: mitosis linked death
– Extent of cell loss depends on damage to the stem cell
pools & the proliferative rate of the cell population

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• LONG TERM EFFECTS:
– Depend primarily on the extent of damage to the
fine vasculature.
– Relative radiosensitivity of capillaries and
connective tissue is intermediate between that of
differentiating intermitotic cells and reverting
postmitotic cells

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Irradiation Swelling,degeneration Increase capillary
of capillaries & necrosis permeability

Initiation of slow
progressive fibrosis
around the vessels

Impairs transport of
nutrients,O2,waste Obliteration of
products Premature narrowing
vascular lumens

Progressive Loss of cell function &

Death of cells
fibroatrophy of the reduced resistance to
irradiated tissue infection & trauma
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• Death of the parenchymal cells after moderate
exposure occurs due to:
– Mitotic linked death of rapidly dividing cells
– Consequences of progressive fibro-atrophy on all
cell types over time

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• RELATIVE RADIOSENSITIVITY OF VARIOUS ORGANS:

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 FACTORS AFFECTING BIOLOGIC
TISSUES
• RADIATION FACTORS • HOST FACTORS
– Rate of dose
– Type of irradiation
– Linear energy transfer
– Fractionization
• Age of the patient
• Type of cell
• Oxygenation
• Nature of irradiated tissue
• Area irradiated
• Latent period
• Recovery power of the tissue
• Stage of development of the
tissue
• Tissue threshold
• Part of the body exposed
• Species & individuals
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 LINEAR ENERGY TRANSFER
• The dose required to produce a certain
biological effect is reduced as LET is increased
• Higher LET radiations more efficient
in damaging biological systems
• When the biologic response to different types
of radiation is compared,it is referred to as
relative biologic effectiveness(RBE)

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RADIATION EFFECT ON ORAL TISSUES

• Oral mucous membrane

• Taste buds
• Salivary glands
• Teeth
• Musculature
• Bone

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 ORAL MUCOUS MEMBRANE
• Basal layer : rapidly dividing,radiosensitive stem cells
• End of second week:appearance of areas of redness &
inflammation
• Formation of white to yellow
pseudomembrane(desquamated epithelial layer)
• End of therapy: mucositis maximum-difficulty in
food intake
• Secondary candidal infection common

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• After irradiation:
– Mucosal healing occurs
– Complete by about 2 months
– Progressive obliteration of the fine vasculature &
fibrosis of the underlying connective tissue
– Atrophic, thin, & relatively avascular
– Complicate denture wearing due to oral ulcerations
of the compromised tissue

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 COMMON SITES

COMMON SITES

Mucosa of the cheek Soft palate

Lips

Ventral surface of
the tongue
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GRADING OF MUCOSITIS

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 MANAGEMENT
• Mainly supportive
• Brush the teeth with a gentle toothbrush two or
three times daily, use a nondetergent
toothpaste, floss between the teeth, and use an
alcohol-free mouthwash
• Artificial saliva spray(Xerotin,moistir) and
water-soluble jellies
• saline or baking soda mouthwash
• Drinking plenty of liquids
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• Avoiding citrus fruits, tomatoes, acidic foods,
alcohol, and hot foods that can aggravate
mucositis lesions.
• Refraining from smoking
• Sucking ice cubes
MAGIC MOUTHWASH
• composed of diphenhydramine,viscous
lidocaine,bismuth,corticosteroids,etc
Palifermin
• recombinant human keratinocyte growth factor

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 LUBRICANTS
• clean and moisten lips and keep them intact.
• KY jelly, vaseline or mineral oil.
Analgesics and anaesthetics
• Diphenhydramine hydrochloride (Benadryl);
Kaopec- tate and milk of magnesia; Benadryl
and Kaopectate; and Xylocaine viscous

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 TASTE BUDS
• Extensive degeneration of the normal histologic
architecture of taste buds
• Loss of taste acquity-2nd to 3rd week
• Bitter & acid flavors : posterior two-third
• Salt & sweet: anterior third
• Acquity: decreases by factor of 1000-10000
• Alteration in saliva contributory
• Reversible: recovery within 60-120 days

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 Salivary glands
• Major salivary glands affected
• Parenchymal component: radiosensitive
• Parotid gland: affected more
• Marked & progressive loss of salivary secretion(
hyposalivation): first few weeks after initiation
• Dose dependent: reaches essentially zero at 60 Gy
• Dry, tender,swallowing difficult & painful

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• Serous cells: more radiosensitive
• The residual saliva is more viscous
• pH value is 1 unit below normal : low enough to initiate
decalcification of normal enamel
• If some portion of major salivary glands spared: dryness
subsides by compensatory hypertrophy
• Histologically:
– Acute inflammatory response involving the serous acini
– After radiation: more chronic
– Progressive fibrosis,adiposis,loss of fine
vasculature,parenchymal degeneration
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• IMRT : spares the contralateral salivary glands- minimizes the
loss of function
• Saliva substitutes
• Systemic sialagogues:
– Pilocarpine (Salagen): only effective for salivary glands
with residual function.
– Cevimeline (Evoxac)
• Sugarless gum or lozenges may stimulate salivary secretion in
patients with residual salivary gland function.
• Sugar-free popsicles, plain ice cubes or ice water may be used
to keep the mouth cool and moist.
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 teeth
• Children:
– Defects in permanent dentition:
• Retarded root development
• Dwarfed teeth
• Failure to form one/ more teeth
– Irradiation precedes calcification:
• Destruction of tooth bud
– After calcification:
• Inhibition of cellular differentiation: malformation & arresting
general growth
• Retard / abort root formation
• Eruption radioresistant

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• Adult:
– Resistant to the direct effects
– Pulpal tissue: long-term fibroatrophy
– No discernable effect on the crystalline structure of
enamel,dentin, or cementum

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 RADIATION CARIES
• Rampant form of caries
• Result from changes in the salivary glands & saliva
– Reduced flow
– Decreased pH
– Reduced buffering capacity
– Increased viscosity

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• 3 types:

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 Management
• Use of fluoride products reduced caries activity
• Avoid dietary sucrose
• Dental restorative materials: conventional GIC restorations
performed poorly than did RM-GIC, composite resin, and
amalgam restorations

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 musculature
• Inflammation & fibrosis
• Contracture & trismus in the muscles of mastication
• Masster / pterygoid muscles involved
• Restricted mouth opening starts about 2 months after
RT
• MANAGEMENT:
• Early Intervention- Heat therapy ,Analgesics , Soft diet
, Muscle relaxants.
• Tongue depressors
• '7-7-7'

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 bone
• Primary damage to mature bone results from
radiation induced vasculature & cortical bone
• Destruction of osteoblasts & osteoclasts
• Normal marrow replaced by fatty marrow &
fibrous CT
• Hypovascular,hypoxic & hypocellular
• Endosteum-atrophic
• Decreased degree of mineralization
• Severe changes-bone death-ORN

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 OSTEORADIONECROSIS
• Most serious complication Resulting
from radiation
Decreased Renders bone induced
vascularity more readily breakdown by
infected mechanical
damage

Non-healing
wound

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• Mandible affected more
• Dose dependent
• Defined as “Exposed irradiated bone that fails
to heal over a period of 3 months without a
residual or recurrent tumor”
• Also known as Post Radiation Osteo
Necrosis(PRON)

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 Signs & symptoms
• Pain
• Swelling
• Exposed bone
• Drainage
• Fistulization to mucosa / skin
• Trismus
• Malocclusion
• Food impaction

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 CLASSIFICATION BY NOTANI et al
GRADE DESCRIPTION

I ORN confined to alveolar bone

II ORN limited to the alveolar bone and/or mandible above the level of the
inferior alveolar canal

III ORN involving the mandible below the level of the inferior alveolar canal
and/or skin fistula and/or pathological fracture

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 MANAGEMENT
• CONSERVATIVE MANAGEMENT
• HBOT
• ULTRASOUND THERAPY
• SURGERY
• TREATMENT ACCORDING TO THE
RADIATION-INDUCED FIBROSIS
THEORY
• OTHER TREATMENT MODALITIES
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 BEFORE AFTER
RADIOTHERAPY RADIOTHERAPY

NON-INVASIVE 20 DAYS 3 MONTHS

PROCEDURES

INVASIVE 30 DAYS 6 MONTHS

PROCEDURES

PROPHYLACTIC ANTIBIOTICOTHERAPY RECOMMENDED

JOURNAL OF APPLIED ORAL SCIENCE:J.APPL.ORAL SCI.VOL.19 NO.5 BAURU
SEPT/OCT 2011

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 Whole body irradiation
• ACUTE RADIATION SYNDROME:
– Prodromal period
– Latent period
– Hematopoietic syndrome
– Gastrointestinal syndrome
– Cardiovascular & central nervous system
syndrome

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• PRODROMAL PERIOD:
– 1-2 Gy
– Cause: unclear, but involves ANS
– Symptoms of gastrointestinal tract disturbances :
anorexia, nausea, vomiting, diarrhea, weakness &
fatigue
– Severity & onset: dose related

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• LATENT PERIOD:
– Apparent well-being
– Dose-related
– Extends from hours / days at supralethal exposures
to a few weeks at sublethal exposures
– Symptoms follow the latent period : lethal range(
approx. 2-5 Gy) or supralethal range

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• HEMATOPOIETIC PERIOD:
– 2-7 Gy: Injury to the hematopoietic stem cells of
the bone marrow & spleen
– Radiosensitive tissue
– Rapid & profound fall in the numbers of
circulating granulocytes,platelets & finally
erythrocytes
– Mature circulating granulocytes, platelets &
erythrocytes: radiosensitive

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• The rate of fall depends on the life span of that
cell in the peripheral blood
• RBCs : fall off slowly ; granulocytes: fall off
rapidly
• Consequence: infection, followed by anemia
• Clinical signs:
– Infection
– Hemorrhage
– Anemia
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• GASTOINTESTINAL SYNDROME:
– 7-15 Gy
– Extensive damage
– In addition to hematopoietic damage:
Gastrointestinal syndrome
– Experience prodromal stage within few hours of
exposure
– Injury to the rapidly proliferating basal epithelial
cells of the intestinal villi
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• CARDIOVASCULAR & CENTRAL
NERVOUS SYSTEM SYNDROME:
– Excess of 50 Gy
– Death in 1-2 days
– Collapse of the circulatory system with a
precipitous fall in blood pressure
– Intermittent stupor,incoordination,disorientation &
convulsions
– Rapid,irreversible course
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• MANAGEMENT OF ARS:
– ANTIBIOTICS : when the granulocyte count falls
– Fluid & electrolyte replacement
– Whole body transfusions: treat anemia
– Platelets: arrest thrombocytopenia
– Bone marrow grafts: between identical twins-no
graft versus host disease

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 RADIATION EFFECTS ON EMBRYOS &
FETUSES
• More radiosensitive
• Most embryonic cells are relatively
undifferentiated & rapidly mitotic

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• LATE EFFECTS:
– Growth & development:
• Impairment of growth & development
• Reduced height,weight & skeletal development
• Younger the individual at the time of exposure: more
pronounced the effects
– Cataracts:
• Threshold: 0.6Gy-5Gy
– Life span shortening:
• Decrease in median life expectancy
• 2 months-2.6 years
• Increased frequency of heart disease, stroke & diseases of the
digestive,respiratory & hematopoietic systems

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 STOCHASTIC EFFECTS
• Result from sublethal changes in the DNA of
individual cells

CARCINOGENESIS

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 CARCINOGENESIS
• Modifies the DNA
• Most likely mechanism : radiation induced gene
mutation
• Acts as initiator,promoter,converts premalignant cells
into malignant ones,loss of function
• Estimation of number of cancers induced by radiation
is difficult

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• LEUKEMIA:
– Rises after exposure of the bone marrow to
radiation
– Atomic bomb survivors & patients irradiated for
ankylosing spondylitis
– Exposure under 30 years :risk of development
ceases after 30 years
– As adults: risk persists throughout life
– Appear sooner than solid tumors
– Younger age group are more at risk
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• THYROID CANCER:
– From follicular epithelium
– Susceptibility to radiation-induced cancer is greater
early in childhood than at any time later in life
– Children: more susceptible
– Females: 2-3times more susceptible
• ESOPHAGEAL CANCER:
– Relatively sparse
– Atomic bomb survivors & ankylosing spondylitis

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• BRAIN & NERVOUS SYSTEM CANCERS:
– X-ray examinations in utero & therapeutic doses in
childhood / adults
– Strongest association: history of exposure of full
mouth dental radiographs when younger than 20 years
• SALIVARY GLAND CANCER:
– Irradiation for diseases in Head & neck,atomic bomb
survivors & diagnostic X-radiation
– Highest in persons receiving full-mouth examinations
before 20 years of age
– Significant correlation: estimated cumulative dose of
0.5 Gy / more
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• CANCER OF OTHER ORGANS:
– Skin,paranasal sinuses & bone marrow

SUSCEPTIBILITY OF DIFFERENT ORGANS TO

RADIATION-INDUCED CANCER
HIGH INTERMEDIATE LOW

Colon Bladder Bone surface

Stomach Liver Brain
Lung Thyroid Salivary glands
Bone marrow Skin
Female breast

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 HERITABLE EFFECTS
• Seen in the offspring of irradiated individuals
• Consequence of damage to the genetic material
of reproductive cells
BASIC PRINCIPLES OF RADIATION GENETICS
•Increased frequency of spontaneous mutations rather than inducing new
mutations
•Frequency of mutations increases in direct proportion to the dose, even at
very low doses, with no evidence of a threshold
•Majority of mutations are deleterious to the organism
•Dose rate is important
•Males are much more radiosensitive
•The rate of mutations is reduced at the time between exposure &
conception increases
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• EFFECTS ON HUMANS:
– Atomic bomb survivors
• Doubling dose:
– Amount of radiation a population requires to
produce in the next generation as many additional
mutations as arise spontaneously
– Humans: 1Sv

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 CONCLUSION
• Advise appropriate radiographs only when
indicated
• Thorough Dental management of patients
irradiated for Cancer

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 References
• ORAL RADIOLOGY:WHITE & PHAROAH
• TEXTBOOK OF ORAL RADIOLOGY:LANGLAND &
LANGLAIS
• ERIC WHAITES: TEXTBOOK OF RADIOLOGY
• JOEN IANNUCCI HARING & LAURA JANSEN
HOWERTON: TEXTBOOK OF RADIOLOGY

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