RADIATION BIOLOGY

Prof.Dr.Sumanth KN
Learning Objectives
Illustrate the effects of radiation at molecular,
genetic, cellular and tissue level. (C3)
Explain the effects of radiation therapy on
oro-facial region. (C2)
Differentiate the deterministic and stochastic
effects of radiation. (C4)
Introduction
Study of effects of ionizing radiation on
living systems

Biologic effects of radiation

1. Deterministic effects
2. Stochastic effects
DETERMINISTIC EFFECTS
Severity of the response is proportional to the dose
There is a dose threshold below which response is not
seen

Examples:

a. Changes in the oral cavity following radiation therapy

(mucositis, radiation caries)

b. Acute radiation syndrome

STOCHASTIC EFFECTS
All or none concept

Probability of changes occurring is dose dependent and not

the severity

They do not have dose thresholds

Example:

Greater the exposure of an individual to radiation increases

the probability of the individual developing cancer and not
the severity of cancer
Effects of radiation on living systems
DIRECT EFFECT photon ionizes biological macromolecules. The
altered molecules differ structurally and functionally, resulting in a
biologic change in the irradiated organism. Approximately one third of the
biologic effects of x-ray exposure result from direct effects. Direct effect
is the most common outcome for particulate radiation

INDIRECT EFFECT photon ionizes water molecules in the organism

Radiolysis of water

Free radicals interact with tissues (biological molecules) and causes changes
 Direct effect (on biologic molecules)
Time taken: 10-10 second after interaction with photon
Free radical production: RH + x-ray = R* + H+ + e-

Free radical fates:

A. Dissociation: R* = X + Y*
B. Cross-linking: R* + S* = RS

RH= R is the molecule and H is a hydrogen atom

Radiolysis of water
Radiation

H2O H2O+ e

The positive ion immediately

H2O+ H+ OH*
breaks up

The electron e attaches to a

H2O e H2O
neutral water molecule

The resulting negatively charged

H2O H* OH
molecule dissociates

H* H* H2 The electrically neutral H and OH

are unstable and highly reactive
and are called as free radicals. They
OH* OH* H2O2 can combine with other free radicals.
Indirect effect (interaction of free radicals with
organic molecules)
About two thirds of radiation induced biologic
damage results from indirect effects.

RH + OH* = R* + H2O
RH + H* = R* + H2
Effects of Radiation
On Biological molecules Nucleic acids
Proteins

Effects at cellular level Nucleus

Chromosomal Aberration
Cytoplasmic changes

Effects on Cell Kinetics Mitotic delay

Cell death
Effects on biological molecules - nucleic acid

Change or loss of base

Disruption of hydrogen bonds between DNA
strands
Breakage of one or both DNA strands
Cross linking of DNA strands (within helix, to
other DNA strands or to proteins)
 Effects on Proteins
Disruption of side chains or breakage of
hydrogen or disulfide bonds
Intermolecular and intra-molecular cross
linking
Chromosomal Aberration

DNA synthesis
+
X-ray

DNA synthesis +
X-ray
 Effects on Cytoplasm

At about 30-50Gy mitochondria exhibit

increased permeability, swelling and
disorganization of the internal cristae
Mitotic Delay, Cell Death & Recovery
Low dose of radiation
G1 induces mild mitotic delay
Gap 1 in G2 cells
S
Mitosis
DNA
Delayed cells pass through
G2
Gap 2 Synthetic mitosis along with non
Period delayed cells (elevated
mitotic index)
Moderate dose- longer
M
Low dose Moderate dose
I
T mitotic delay (G2 block)
and some cell death
O
T
I
C

I Larger doses Profound

Large dose
mitotic delay with
N
D
E
X

12 24
incomplete recovery
Time (hours)
Effects of Radiation in the Oral Tissues
Oral Mucous Membrane
Salivary Glands
Taste buds
Teeth
Bone
 Oral Mucous Membrane
Basal layer - vegetative and differentiating
intermitotic cells (radiosensitive)

3nd week after therapy- redness and

Inflammation (Mucositis)

White /yellow pseudo membrane, Candidal

super infection

Management
Maintenance of good oral hygiene
Topical viscous xylocaine prior to food intake
Condition usually resolves in 2 months post RT
 Salivary Glands
Radiation induces fatty degeneration, fibrosis, acinar atrophy
and cellular necrosis within the glands
Serous acini are more radiosensitive
Reduced saliva, thick and ropy
Xerostomia- may reverse in 6 -12 months
Irreversible effects occur at a total dose of 6,000 Gy for 5
weeks

Management
Frequent sips of water, sugarless chewing gum, pilocarpine
hydrochloride (5mg 4 times a day), bethanechol 25-
200mg/day
 Effects on Taste Buds
Cells in the taste buds are damaged/ innervating nerve fibers
are damaged
Partial or complete loss of taste if taste buds are irradiated
Alteration in taste for sweet, sour, bitter and salt
Generally cells regenerate in 4 months

Management
Dietary consultation-improve quality of food
Zinc sulphate capsules- 220mg twice daily with food,
elemental zinc- 100mg
 Radiation Caries
Reduced salivation/change in chemical composition.
Cervical areas are most affected followed by cuspal/ incisal
tips

Three types
Dark pigmentation of crown
Circumferential caries generally involves cervical third
(amputation caries)
Wide spread superficial caries

Management
Hydrogen peroxide rinses 3% (maintenance of oral hygiene)
Topical fluoride applications
 Osteoradionecrosis
Radiation therapy causes endarteritis obliterans -
hypovascular, hypocellular, and hypoxic tissue
mandible most commonly involved (can occur in the maxilla
Predisposing factors
trauma (from surgical procedures)

active periodontal disease or denture trauma, idiopathic or

spontaneous necrosis

Presence of teeth in a high-dose radiation field associated

with dental or periodontal disease or irritation
 Osteoradionecrosis

Symptoms & signs

discomfort or tenderness
bad taste, paraesthesia and anesthesia
extra oral and oroantral fistulae, secondary infection
pathologic fracture

Considerations
If extractions are planned, it is desirable to allow as much healing
time as possible; 7 to 14 days and up to 21 days have been
suggested as healing times prior to radiotherapy
Post radiation therapy, extractions should be delayed at least for 6
months to one year
 Effects on Teeth
Retardation of growth of teeth
Radiation before calcification- destroys tooth
bud
Radiation after calcification- malformation
Dwarfed teeth, retarded root formation, absence
of teeth
Pulp may exhibit long term fibro-atrophy post
irradiation
Eruption process and erupted teeth are
generally radio resistant
Radiation Caries
Whole body radiation
Acute Radiation Syndrome

Dose in Manifestations
Gy
1-2 Prodromal symptoms
2-4 Mild hematopoietic symptoms
4-7 Severe hematopoietic symptoms
7-15 Gastrointestinal symptoms
>50 Cardiovascular and CNS symptoms
 Acute Radiation Syndrome
Prodromal symptoms
minutes to hours after exposure
anorexia, nausea, vomiting, diarrhea,
fatigue and weakness

Latent period
extends from hours to days
patient is apparently normal
 Hematopoietic Syndrome
Radiation causes damage to hematopoietic cells of bone
marrow & spleen
Remarkable fall in the no. of granulocytes, platelets and
erythrocytes

Clinical signs: Infection, hemorrhage & anemia

Death may occur 10 to 30 days after radiation

Management: removal of sources of infection, antibiotics

and bone marrow transplantation
 GI Syndrome
Rapidly proliferating basal epithelial cells of
the intestinal villi are damaged
Loss of epithelial layer of the intestinal
mucosa loss of plasma & electrolytes
Reduced efficiency of intestinal absorption
Ulceration and hemorrhage in the intestines
Bacteria invade denuded areas septicemia
Diarrhoea, dehydration, loss of weight
 CVS and CNS syndrome
Irreversible condition
> 50 Gy causes death in 1- 2 days
Circulatory system collapses, drastic fall in
BP
Incoordination, disorientation, and
convulsions
 Radiosensitivity of various organs
High Intermediate Low
Bone marrow Salivary glands Muscle cells
Lymphoid organs Lungs Neurons
Testes Kidney Mature
(spermatocytes) erythrocytes
Intestines Liver Optic lens
Mucous Growing Bone Squamous
membrane epithelial cells
Growing cartilage
 Susceptibility of Tissues to Radiation Induced
Cancer
High risk Moderate risk Low risk
Bone marrow Breast Skin
Lung Esophagus Bone surface
Stomach Brain
Colon Salivary Glands
Bladder, Liver
Thyroid
THANK YOU