RADIATION BIOLOGY

OR
RADIOBIOLOGY
 INTRODUCTION

• The branch of science which studies the effects of

radiation on the human body or living tissues –
“RADIOBIOLOGY”
• Radiobiology is the study of the effects of ionizing
radiation on living systems
• DIRECT AND INDIRECT EFFECTS
 DIRECT EFFECTS

1/3rd of biological effects of x-ray exposure result

from direct effects
 INDIRECT EFFECTS
• Radiolysis of water
• Water – hydrogen & hydroxyl free radicals
• 2/3rd of radiation induced biologic damage
 DNA CHANGES
• Breakage of 1 or both DNA strands
• Cross-linking of DNA strands within the helix to other
DNA strands or to proteins
• Change or loss of a base
• Disruption of hydrogen bonds between DNA strands
• Clusters of double-strand damage in DNA
• Cluster – 2 or more double strand breaks within 2
turns of DNA
 DETREMINISTIC & STOCHASTIC EFFECTS

• Results from either the killing of large numbers of cells

• Sublethal damage to the genome of individual cells

 COMPARISION OF DETREMINISTIC & STOCHASTIC
EFFECTS
Deteministic Effect
Caused by Killing of many cells
Threshold dose Yes. Sufficient cell killing
required to cause a clinical
response
Severity of clinical effects & Severity of clinical effects is
dose proportional to dose, the
greater the dose, the greater
the effect
Probability of having effect & Probability of effect
dose independent of dose, all
individuals show effect when
dose is above threshold
Stochastic Effect
Sublethal damage to DNA
No. Even one photon could
cause a change in DNA that
leads to a cancer or heritable
effect
Severity of clinical effects is
independent of dose, all-or-
none response – an
individual either has effect or
does not
Frequency of effect
proportional to dose, the
greater the dose, the greater
the chance of having the
effect
 DETERMINISTIC EFFECTS ON CELLS

INTRACELLULAR STRUCTURES

Structural
Radiation CELL
and Cellular
induced Macromolecules DEATH
Functional organells
changes
changes
NUCLEUS & CHROMOSOME ABERRATIONS
 CELL REPLICATION
• MECHANISM OF CELL REPLICATION
– DNA damage
– Bystander effect
– Apoptosis
• DNA DAMAGE
– Slowly dividing cells is irradiated –
larger doses & longer time
• BYSTANDER EFFECT
– Kill nearby cells
• APOPTOSIS
– Programmed cell death
 DETERMINISTIC EFFECTS ON TISSUES &
ORGANS
• SHORT TERM EFFECTS
– 1st day or weeks after exposure
• LONG TERM EFFECTS
– Months & years after exposure
• MODIFYING FACTORS
– DOSE
• Amount of damage is proportional to dose
– DOSE RATE
• Rate of exposure
• Dose at high dose rate causes more damage
– OXYGEN
• Radioresistance increases with reduced oxygen
RADIOSENSITIVITY OF VARIOUS TISSUES
INTENSITY EFFECT
Bone Marrow
High Radiosensitivity Basal cell of oral mucous membrane
Inner enamel epithelium of developing tooth
Lymphoid organs
Fine vasculature
Growing cartilage

Intermediate Radiosensitivity Growing bone

Salivary glands parenchymal cells
Fibroblasts
Cranial nerves
Low Radiosensitivity Muscles
Surface cells of oral mucous membrane
RADIOTHERAPY IN THE ORAL CAVITY
 EFFECT ON ORAL TISSUES
• 2 Gy daily for weekly exposure of 10 Gy
• Radiotherapy – 6-7 weeks – total of 60 – 70 Gy
• IMRT – intensity modulated radiotherapy
 ORAL MUCOUS MEMBRANE
• Basal layer – radiosensitive cells
• 2nd week – redness & inflammation – MUCOSITIS
• Irradiated mucosa – separate – white to yellow
pseudomembrane – DESQUAMATED EPITHELIAL
LAYER
• End of therapy – Mucositis severe, discomfort is
maximum
• After irradiation – mucosa begins to heal
• Healing – 2 months
• Atrophic, thin & relatively avascular
• Fibrosis of underlying connective tissue
• Atrophic changes – denture wearing – oral ulcerations
 TASTE BUDS

• Sensitive to radiation
• Extensive degeneration of normal architecture
• Loss of taste – 2nd & 3rd week
• Bitter & acid flavours – posterior 2/3rds
• Salt & sweet – anterior 1/3rd
• Reversible – recovery – 60-120 days
 SALIVARY GLANDS
• 20 – 30 Gy - radiotherapy
• Parenchymal component – radiosensitive
• 1st few weeks – progressive loss of saliva
• 60 Gy – zero
• Xerostomia, tender & difficulty in swallowing
• Marked loss of serous acini & progressive fibrosis –
xerostomia
• Irradiation of both parotid glands
• Saliva – more viscous
• pH below normal (6.5 – 5.5 )
• Low pH – decalcification of
normal enamel
• Compensatory hypertrophy of residual salivary gland
tissue
• 6-12 months
• More than 1yr – unlikely to
recovery
 TEETH
• Damage - dose dependent
• Children
– Retarded root development
– Dwarfed teeth
– Failure to form 1 or more teeth
• Precedes calcification – destroys tooth buds
• After calcification – inhibit cellular differentiation
– Malformations
– Arresting growth
– Retard or abort root formation
• Eruptive mechanism - radioresistant
 RADIATION CARIES

• Changes in salivary glands & saliva

– Reduced flow
– Decresed pH
– Reduced buffering capacity
– Incresed viscosity
– Altered flora (S.mutans, lactobacillus & candida)
– Low calcium ions – greater solubility & reduced
remineralization
• Rampant form
• 30 Gy – worsens – 60 Gy
• 3 types
– Widespread superficial lesions - all surfaces
– Cementum & dentin – cervical region – loss of crown
– Dark pigmentation of the entire crown, incisal edges
worn out
• RC – periapical inflammation – high dose
 BONE
• Radiation - vasculature of periosteum & cortical bone
• Radiation greated than 60 Gy

• Destroys osteoblats & osteoclasts

• Endosteum – atrophic

• Lack of osteoblastic & osteoclastic activity

• Degree of mineralization reduced

• Leading to brittleness

• OSTEORADIONECROSIS
• Other complications
– Trismus
– Loss of taste
– Difficulty in swallowing
– Xerostomia
 MUSCULATURE

• Inflammation & fibrosis – contracture & trismus

• Masseter & pterygoid
• Restriction of mouth opening – 2months
DETERMINISTIC EFFECTS OF WHOLE
BODY IRRADIATION

ACUTE RADIATION EFFECTS

RADIATION ON
SYNDROME EMBRYOS & FETUSES

LATE EFFECTS
ACUTE RADIATION SYNDROME
• PRODROMAL PERIOD
– 1st min –hrs
– 1.5 Gy
– Anorexia
– Nausea
– Vomiting
– Diarrhea
– Weakness
– Fatigue
• LATENT PERIOD `
• Signs & symptoms free
• Dose related – supralethal exposures (>5Gy-2Gy)
• HEMATOPOIETIC SYNDROME

2 -7 Gy
Injury – hematopoietic
stem cells
Granulocytes
Platelets
Erythrocytes

• CLINICAL SIGNS
– Infection – lymphopenia & granulocytopenia
– Hemorrhage
– Anemia
• Death – 10-30 days
• GASTROINTESTINAL SYNDROME
7 – 15 Gy – damage to GI

Basal epithelial cells – intestinal villi

Loss of epithelial layer of intestinal mucosa

Loss of plasma & electrolytes

Loss of absorption, ulceration – hemorrhaging -

intestines

Diarrhea, dehydration , weight loss

Endogenous bacteria

SEPTICEMIA
• CVS & CNS SYNDROME
– 50 Gy – death – 1 to 2 days
– Fall in BP
– Necrosis of cardiac muscles
– Symptoms
• Intermittent stupor
• Incoordination disorentation
• Convulsions
 RADIATION EFFECTS ON EMBRYOS &
FETUSES
• Radiosensitive
• 1 -3 Gy 1st few days of conception – death
• Abnormalities
– Microcephaly
– Mental retardation
– Small birth size
– Cataracts
– Genital & skeletal malformations
– Leukemia
 LATE EFFECTS

• GROWTH & DEVELOPMENT

– Reduced height, weight & skeletal development
• CATARACTS
– 0.5 Gy
• SHORTENED LIFE SPAN
– Shortened life expectency
– Heart disease, stroke & noncancer diseases
STOCHASTIC EFFECTS
 CARCINOGENESIS
• Radiation – Cancer – modifying DNA

Accumulation of radiation
induced gene mutations

Involve growth regulating

genes

Deregulate cell growth or

differentiation

Neoplastic development