BIOLOGICAL EFFECTS OF

IONIZING RADIATION

Kadambini Devi
Radiological Safety Division
Atomic Energy Regulatory Board
Email: kadambinidevi@aerb.gov.in

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 Contents
 Introduction

 Radiation Interaction with cells

 Biological effects of radiation

 Summary

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 Early Observations of the Effects of
Ionizing Radiation
• 1895 X-rays discovered by Roentgen
• 1896 First skin burns reported
• 1896 First use of x-rays in the treatment of cancer
• 1896 Becquerel: Discovery of radioactivity
• 1897 First cases of skin damage reported
• 1902 First report of x-ray induced cancer
• 1911 First report of leukaemia in humans and lung
cancer from occupational exposure
• 1911 94 cases of tumour reported in Germany (50
being radiologists)
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 Radiobiological Data
 Studies on
 Micro-organism
 Cultured Mammalian Cells
 Whole Animal Systems
 Human Data
 Survivors of Atomic Bomb Explosions
 Inhabitants of Marshall Islands (fall out of thermo nuclear
devices)
 Uranium Miners
 Radium Dial Painters
 Pioneer of X-ray technicians and radiologists
 Patients exposed to radiation for medical reasons
 Victims of nuclear accidents

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 Cells in our body
 Cell : Basic unit of life
 The human body contains about 1014 cells.
 Cells are of different size and shape in
different parts of the body
 Cells of similar nature are organized to
form a tissue
 Different tissues join to form an organ

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 Cell Structure
Cytoplasm

Cell
Membrane

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 Nucleus of Cell
It is the ‘control room’ of the ‘cell factory’

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 Nucleus  Chromosomes DNA

 Somatic Cells : 46 chromosomes (23 pairs)

 Genetic/germ/reproductive cells

 Male sperm, Female ova :

(only 23 chromosomes)

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 Classification of cells
 Somatic Cells
 Constitute various tissues such as brain,
lungs, skin, kidney, eye etc.
 Consists of 46 chromosomes (23 pairs)

 Germ Cells (Reproductive Cells)

 Cells, which participate in reproductive
process i.e. sperms in males and ova in
females
 Consist of 23 chromosomes (not in pair)

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 Radiation interaction  At cellular level

 Direct interaction : Direct damage to cell

structure; single or double strand break in DNA
structure  Chromosome aberration
 Indirect interaction  Radiolysis of water in
cells production of hydrogen peroxide ,
hydrogen and hydroxyl ions and radicals
interaction of radicals with DNA

The critical target: DNA

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 Direct action

α and β (Bond breaks) Indirect action

H OH-
X ray O H+
H Ho
 ray
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OHo 11
 Damage to DNA
Base alteration

Single Strand Double Strand

Break Break

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 If few cells are killed, they can easily be replaced.

 If too many cells are killed, the organ or body will

die.

 If cells are damaged but not killed, the body will try
to repair them, using the DNA as template.

 Repairs may be correct or wrong

 If repair is incorrect, the cell may survive but the

biological program of the cell may change
(Mutation)
 This may eventually be the origin of cancer
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 Biological Effects depend on

 TYPE OF Radiation –Low LET/ High LET

 Type of Exposure :Acute or Chronic
 Type of cell involved :Somatic or Germ
 Type of tissue involved
 Type of irradiation : Whole body or
localized
 Sensitivity of Individual

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Survival curve for mammalian cells exposed

to high- (A) and low-LET (B) radiation

B
A

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 RADIATION EFFECTS AT CELLULAR LEVEL
Inhibition of cell division
 Radiation induce damage may delay or inhibit the
process of cell division, which may impair the functions
of tissues or organs
 Chromosome aberrations
 Lead to rearrangement of genetic information, which may lead to
cell death or altered cellular functions. The frequency of CA can be
correlated to dose and hence serve as biological dosimeter
{detectable above 100 mSv ( 0.1 Gy)}
 Gene mutation
 Alteration in the information content of genes. Damage
to chromosomes may lead to gene mutations.
 Cell death
 Irradiation can lead to cell death. It is usually expressed as
fraction of cells surviving after a given exposure
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 Relationship between cellular level damage and
biological effects

Cellular Level Dam age

Cell Killing Cell M odification

Radiation Sickness Som atic Cells M utations in

M anifest illness Cell transform ations G erm cells
m utations

Death due to Com plete recovery Carcinogenesis G enetic effects

bone m arrow depletion w ithin m onths am ong a few of the w hich m ay appear in future
or G I dam age Dam age to individual organs exposed several years later generation

M anifestation of late effects

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 BIOLOGICAL EFFECTS
Direct Indirect
effects effects

Primary Repair
damage

Cell death Modified Cell

Damage to organ Somatic cells Germ cells

Death of organism Cancer / Leukemia Hereditary effects

Deterministic effects Stochastic effects

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 Biological effects of ionizing
 Deterministic
radiation
 occurs beyond a threshold dose severity
of the effect increases with increase in dose.
- e. g. Cataract
 Stochastic
 Statistical/probabilistic in natureNo
threshold dose Chance for occurrence
increases with increase in dose
 e.g Cancer, genetic effects.

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 RADIATION EFFECTS (Somatic)

Deterministic effects
• Due to cell killing
Severity of • Have a dose threshold -
effect typically several Gy
• Severity of harm is dose
dependent
threshold dose
Dose (Gy)

Example: Skin reddening (erythema), Skin breakdown

(desquamation), Cataract of the lens of the eye, Sterility
(Temporary/Permanent), Death due to acute radiation syndrome
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 Examples for deterministic effects

 Skin reddening (erythema)

 Skin breakdown (desquamation)
 Cataract of the lens of the eye
 Sterility (Temporary/Permanent)
 Death due to acute radiation syndrome
(whole body)

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 Note on threshold values
 Depend on dose delivery mode:
 single high dose most effective
 fractionation increases threshold dose in most
cases significantly
 decreasing the dose rate increases threshold
in most cases
 Threshold may differ in different persons

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DETERMINISTIC EFFECT

 Mechanism is cell killing Radiation Sickness -NVD

 Has a threshold dose Radiation syndromes
 Deterministic in nature  Haematopoietic
syndrome
 Severity increases with dose  GI syndrome
 Occurs only at high doses  CNS syndrome
 Can be completely avoided Damage to individual
 Proportional relationship organs
between radiation exposure Death
and the effect Late damage
 Sure to occur at an adequate
dose

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 Threshold Doses for Deterministic
Effects
 Cataracts of the lens of the eye
2-10 Gy
 Permanent sterility
 Males 3.5 -6 Gy
Severity
of effect
 Females 2.5-6 Gy
 Temporary sterility
 Males 0.15 Gy
dose
 Females 0.6 Gy
threshold
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 Deterministic effects
 Deterministic (Threshold/non-stochastic)
 Existence of a dose threshold value (below this
dose, the effect is not observable)
 Severity of the effect increases with dose
 A large number of cells are involved

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 EFFECTS OF CELL DEATH
Probability of death
100%

Dose
(mSv)

D
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 Stochastic (Probabilistic)
effects of radiation
 Occurs by chance
 Probability increases with dose

Carcinogenesis

Mutagenesis

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 Stochastic (Probabilistic) Effects
 Due to cell modification
 Have a no threshold dose
 Probability of the effect increases with dose
 Generally occurs with a single cell
 e.g. Cancer, genetic effects

Probability
of Effect

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Dose (Gy)
 Stochastic effects
 Due to cell changes (DNA) and proliferation
towards a malignant disease
 Severity (example cancer) independent of the
dose
 No dose threshold - applicable also to very small
doses
 Probability of effect increases with dose

Probability
of effect

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 Stochastic effects
 Stochastic effects observed in animal
experiments
 Dose-effect relationship for humans can be
studied only in human population groups

 Dose-effect relationship in low dose range

(below 100 mSv) not yet verified
 Extrapolation down to zero excess dose
accepted only for radiation protection and
safety

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 CANCER ( Late somatic effects)
The somatic cell, which suffered gene
mutations and chromosome aberrations, be
transformed to cancer cells.

Latent period 2-30 years or more for lung,

bone cancer.

. Hereditary Effects (germ cell effects)

Occur in the descendants of exposed persons.

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 Comparison of Radiation Effects

DETERMINISTIC EFFECT STOCHASTIC EFFECT

Mechanism is cell killing
Has a threshold dose
Deterministic in nature
Severity increases with dose
Occurs only at high doses
Can be completely avoided
Causal relationship between
radiation exposure and the effect established at low doses
Sure to occur at an adequate
dose
Mechanism is cell modification
Has no threshold
Probabilistic in nature
Probability increases with dose
Occurs even at low doses
Cannot be completely avoided
Causal relationship cannot be
Occurs only among a small
percentage of those exposed

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 Comparison of Radiation Effects
DETERMINISTIC EFFECT
Radiation Sickness
Radiation syndromes
Haematopoietic syndrome
GI syndrome
CNS syndrome
Damage to individual organs
Death
Late damage
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STOCHASTIC EFFECT
Chromosomal damage
Cancer Induction (Several
years after exposure to
radiation)
Genetic Effects (Hereditary
in future generations
only)
Somatic Mutations
33
Biological Effect of Radiation in Man

 The detrimental effects of radiation in human

body are produced as result of damage to
individual cells
 Categorized as per the cell affected
 Somatic Effect
 Early Effect
 Late Effect

 Hereditary (Genetic) Effect

 Late Effect

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 BIOLOGICAL EFFECTS

Damage to cells Somatic Hereditary (Genetic) effects

in tissue effects

Affect health of
Damage to
irradiated Early
germ cells
person Late
effects Effects
Affect the health
Eg. Cataract of offspring
and cancer
Whole Body
Local (Partial Body)
irradiation Irradiation

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 Delayed effects of radiation
SOMATIC Effect:
 arise from damage to cells in
particular tissue
 they affect the health of the irradiated
person.
 They are mainly different kinds of cancer
(leukemia is the most common, with a
delay period of 2-5 years, but also colon,
lung, stomach cancer…)

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 Delayed effects of radiation

Hereditary (Genetic) Effect :

 This effect is due to damage to germ cells

 They affect the health of the offspring of

the irradiated person, if same germ cells

participate in the process of fertilization.

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 Somatic Effect
 Early Somatic Effect
1. Whole Body irradiation
2. Local ( Partial Body) Irradiation

 Late Somatic Effect

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 Early Somatic Effect
-Whole Body Exposure ( Acute)
 Early Somatic Effect may appear
immediately (within a few hours to weeks)
 It is due to acute exposure
: Large dose received over a short period of time
 Depletion of cell population due to cell-
killing

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 Whole body Exposure (Acute)
Dose Range Immediate Effect
Less than 0.1Gy No detectable effect
Above 0.1 Gy Chromosome aberrations detectable
Above 0.5 Gy Reduction in WBC count
(Lymphocyte)
About 1 Gy Transient reduction in WBC count

Radiation sickness in the form of

Nausea, vomiting, diarrhea (NVD)

Above 3 Gy  Irrecoverable damage to blood

forming organs (eg. Bone marrow,

spleen)
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Possibility of death in few weeks
40
 Blood count depression
100 5 Sv dose

50
%
of
norm al
count

50 100
D ays after exposure

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 Whole body Exposure (Acute)
Dose Immediate Effect
Range
3 – 5 Gy Lethal Dose (LD50/60), eg. Anemia,
infection, high fever are main symptoms
7 – 10 GI (gastrointestinal) system get severely
Gy damaged leading to diarrhea, loss of
appetite, weight loss and high fever
Death occurs in 2 to 5 days time
About Damage to Central Nervous System
50 Gy (CNS) leading to depression, fatigue,
coma. Death occur within few hours to
days
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 Lethal Dose, LD50/60
 “Dose which would
cause death to 50% of
the population in 60
days”.
 Its value is about 3-5 Gy
for humans for whole
body irradiation.

Exhibit symptoms such as Nausea, Vomiting, Diarrhea (NVD) with in

one or two hours depending upon the severity

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 Whole body response
(Acute irradiation syndrome)

(death in a few weeks)

3-7 Gy
(death in 7-14 days)
7-10 Gy

(death in 2 days)
Survival time

> 25 Gy

BONE
MARROW GASTRO
INTESTINAL
CNS
(central nervous
system)

Dose
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 Blood picture changes

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 Early Somatic Effects- Local
Irradiation
Effects on Reproductive organs

Dose Region Effect

Range
0.15 Gy Testes in Temporary Sterility
3.5 - 6.0 Gy male Permanent Sterility

1.5 - 2 Gy Ovaries Temporary Sterility

2.5 - 6 Gy in Permanent Sterility
Female
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 Early Somatic Effects-Local irradiation

Dose Region Effect

Range
3 Gy Hair Temporary Epilation
follicles
5 Gy Eye Cataract (after 5-10 yrs)
6 Gy Skin Skin Erythema
(change in Skin colour)
10 -20 Gy Skin Burns, Blisters, Wounds,
Necrosis, Permanent hair loss

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 Radiation Accidents

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Occupational radiation burn following approximately three weeks of
exposure to radiation emitted from nested voltage electron beam
accelerator being tested to kill bacteria.
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04/24/22 50
 Late Somatic Effect
 Person who recover from early effects may still
develop other type of effects in later in life
 The chronic exposure ( low levels of radiation over long
periods of time ) may lead to late effect
 Late effects are characterized by latent period,
as long as 30 years.
E.g. Cataract and cancer

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 Late Somatic Effects
 Cataract :
Cataract is loss of vision, since no blood
flow through lens, dead cells are not
removed, accumulate at same place and
become opaque and lead to impairment of
vision.
Dose : 2-5 Gy
Latent Period: 5-10 years

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 ICRP Recommendation
April 21, 2011
 Lens of the eye, threshold dose is now
considered to be 0.5 Gy (against 0.5 to 2
for detectable opacities and 5 for visual
impairment) .
 Occupational Exposure Lens of Eye Limit
 20 mSv in a y (against 150),
averaged over defined periods of 5 y,
with no single y exceeding 50 mSv
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 Late somatic effects
CANCER ( Late somatic effects)

• The somatic cell, which suffered gene mutations and

chromosome aberrations, be transformed to cancer cells

• Cancer cells multiply and grow in uncontrolled manner

• Latent period : 2-5 years for Leukemia ( blood Cancer)

to 30 years or more for lung, bone cancer.

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 FACTORS MODIFYING THE DAMAGE
A number of physical and biological parameters may
modify the dose effect relationship of early somatic
effect
PHYSICAL
RADIATION QUALITY
DOSE RATE AND DOSE FRACTIONATION
PARTIAL -BODY VS WHOLE-BODY
 CHEMICAL
OXYGEN,
CHEMICAL SENSITIZERS and PROTECTORS
REPAIR INHIBITORS
 BIOLOGICAL
ABILITY TO RECOVER FROM DAMAGE
TYPE OF CELLS, CELL STAGE,
GENETIC MAKE UP
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 FACTORS MODIFYING THE DAMAGE

PHYSICAL
 Age :
- Very young and Old persons are more
sensitive than healthy young adults
- Children are more sensitive to radiation
as their cells are fast multiplying.
 Type of radiation : High LET ( n, alpha) are more
effective than Low LET radiation (gamma rays, beta)
 Fractionation : Dose is less effective if it is fractionated,
since repair of radiation damage can occur between two
exposures

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 FACTORS MODIFYING THE DAMAGE
CHEMICAL
1. Low pH and low temperature decreases cell
death
2. Oxygen present during irradiation sensitizes
the cells
3. Hypoxic condition (absence of oxygen)
during irradiation decreases cell death
4. Presence of radio protective agent
decreases the extent of cell death

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FACTORS MODIFYING THE DAMAGE
BIOLOGICAL :
Radio-sensitivity of different tissues
 Tissues with fast multiplying cells are more
radiosensitive
e.g . Bone marrow, inner skin layer of
intestine etc.
 Tissues with highly differentiated cells are
least sensitive
e.g. nerve cells, brain, muscle etc.
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Treatment of Radiation Sickness
 Dose > 1Gy, Radiation sickness
Effect: NVD and depression in blood counts
Treatment : The effect is transit in nature
and
disappear after a few days
 Dose > 10 Gy,
Effect: Damage to blood forming organs,
Treatment: Since patient is susceptible to
infection, maintenance of sterile condition,
treatment with antibiotics, transfusion of
blood elements like platelets, bone marrow
transfusion etc.
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 Life-time risk (Stochastic Effects)
Effect Risk per million Spontaneous
per mSv risk per million
(Other
practice)
Cancer 50 1x10-5 – 2x10-5

Hereditary 10 10% of all live

born children

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 Life-time risk (Stochastic
Effects)
 Risk per million per mSv:
i.e. If each of 1 million persons ( both men and
women) receive a dose of 1 mSv, the number of
fatal cancer attributable to radiation would be 50
and appear over a period of few decades.
 10 per million live births per mSv due to
irradiation of either parent
 10% of all new born children suffer from
spontaneous genetic disorder

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 RISK Perspective
Relative risk of 1 in a million chances of dying
 Driving 64 km in a car (accident)
 Flying 4023 km in a jet (accident)
 Receiving ~ 0.1 mSv of radiation exposure
 A dose of 1 mSv/a corresponds to a risk to die on
radiation induced cancer of ~ 50 deaths per million
people (5 % per Sv)
 The average risk to die on cancer without
irradiation is about 20 %.

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 Hereditary Effects
Hereditary Effects (Late germ cell effects)
 Occur in the descendants of exposed
persons if germ cells carrying radiation
induced damages (mutation, CA etc.)
participates in the process of
fertilization
 No human data available, based on

animal experiments

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 Occupational Radiation Dose
 Annual Occupational dose mSv/year
for various jobs
- Air Crew (Cosmic) 4.0
- NPP workers 2.5
- Medical Personnel 0.5
- Mining 6.0
- Industrial Radiography 1.5
- Research 0.8

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 Summary
 Biological effects of radiation is the result of damage
initiated by free radicals.
 The effects produced depend upon physical,
chemical and biological factors.
 The effects may be somatic or hereditary in nature.
 The effects can be deterministic or stochastic.
 Acute exposure may cause both immediate and
delayed effects. Chronic exposure results only
delayed effects.

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 Questions
 What is difference between Stochastic and Deterministic
Effect ?
 Give the examples of Stochastic and deterministic effect
 Large amount of cell killing leads to ------effect
 Cell modification leads to -----effect
 What is threshold dose for CA ?
 What is mean by LD50/60
 What are the effects at various doses
 What is mean by Chronic and Acute Exposure
 What is dose range for Cataract

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 Thanks for your kind
attention

Any Question?
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