Biological Effects of Radiation

Objectives
1. Basic mechanism of radiation damage in human body

2. Factors affecting extent of the damage

3. Various health effects of radiation damage

 Whole body exposure effects: Acute radiation syndrome

 Localized exposure effects

 Long term effects Cancer and Genetic risk

Basic organization of human body

• All the organs/tissues are made

up of cells
• Cells are structural and functional
unit of our body
• All the matter in cells is made up
of atoms
 The relative scale of biological molecules and
structures

• Size of alpha 1.67 X 10-15 m

• Size of a cell 1 X10-5 m (~10 m)
• Size of an atom: 1X 10-12 m
• Size of radiation: too small w.r.t. whole cell
• Radiation hits on atoms of molecules of cells

Radiation hitting on human body = radiation passing through atoms of biomolecules inside
our cells
Radiation acts at atomic level to cause effects at higher level
Organization Biological effects of
of human body Radiation
Body Visible Health effects

Systems

Organs

Tissues Tissue reactions

Cells Cellular effects

Bio-molecules Molecular damage

Radiation damage could be direct or indirect
Atoms Ionization  Direct Effect: Radiation hits directly or primary
electrons from ionizations in the vicinity of
biomolecules cause the damage.

 Indirect Effect: Radiation interacts with water

Ionizing Radiation present in cells generates reactive oxygen species
(ROS). ROS are capable of damaging biomolecules
 IR Radiolysis of Water

• Ions: always have charge negative or positive may or may not have unpaired electrons

• Free radicals: always have unpaired electrons could be charged or neutral e.g., O 2-o

(superoxide radical), OHo (Hydroxyl radical)

• ROS could be radical or non-radical, could be charged or neutral
 DNA as the most important target for Radiation

 Stores information for all the functions of cell and lives lifelong inside a cell.
 Genetic material: Passes on information from cell to daughter cell and parents to
progeny
 Damage to DNA is highly detrimental to cell which may lead to
 Cell death
 Modification of cell: transformation into cancer being the most dangerous
modification
 Delay or arrest of cell division
 Extensive DNA repair mechanisms to take care of minor DNA damages efficiently
 Heavy DNA damage leads to mis-repair which may translate into cellular level of effects
 Dividing cells have higher amount of DNA and more chances of DNA damages hence
they are most sensitive to radiation
Chromosomal aberrations are formed
from DNA mis-repair
Red arrow:
Dicentric/Ring
Chr.

Blue Arrow:
Acentric frag.
Note: Dicentric
chromosomal aberration
assay (CA-test) is performed
for suspected overexposure
cases above 100mSv (cases
referred to BARC through
AERB).
With advancements in
biodosimetry dose
No translocation Reciprocal translocation
between Chromosome, 1 estimations can be done
among chromosome
1 red, 2 green & 4
red, & 4 yellow same day after blood
yellow collection.
 Major consequences of DNA damage

Complete Repair Mis-Repair

No effect Cell Death Cell Modification

 Timing of Events leading to Radiation Effects
1 0 -15 Energy deposition
Excitation/ionization PHYSICAL INTERACTIONS
1 0 -12 Initial particle tracks

Radical formation
1 0 -9
Diffusion, chemical reactions PHYSICO-CHEMICAL INTERACTIONS
Initial DNA damage
1 0 -6
T IM E (se c )

1 0 -3 1 ms DNA breaks / base damage

100 1 secon d
Repair processes
Damage fixation
103 Cell killing
BIOLOGICAL RESPONSE
1 h ou r
1 d ay Mutations/transformations/aberrations
106 Proliferation of "damaged" cells
1 y ear Promotion/completion

109 Teratogenesis MEDICAL EFFECTS

Cancer
1 00 y ears Hereditary defects
 Factors determining extent of radiation damage
1. Dose & Dose rate: Higher the dose and dose rate higher the damage
1.0

1.2

0.8 Acute
1.0

Fission neutrons

Dicentric yield
Dicentric + Ring yield

0.6 0.8
-1
2 Gy h
0.6
HTO  rays -1
0.4 1 Gy h
X - rays 0.4 -1
0.5 Gy h
0.2  - rays 0.25 Gy h
-1
0.2
-1
0.1 Gy h

0.0 0.0
0 1 2 3 4 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

Dose (Gy) Dose (Gy)

2. Types of radiation: High LET or Low LET

Linear energy transfer (LET): Energy Relative biological effectiveness (RBE): Ratio
deposited per unit length of doses of Co-60 Gamma vs. test radiation
L=dE/dl required to produce same biological effect (for
Unit: KeV/m e.g., 50% cell killing)

Low LET: Gamma, X-rays, electrons, high

energy protons

High LET: Alpha, neutrons, low Energy

protons, heavy ions
 2. Types of radiation: High LET or Low LET cont…

At 100 keV/m LET is optimum for DNA

Damage as the distance between two
ionizations matches with the diameter of DNA

1. RBE increases initially with LET reached 1. High LET radiations are more
maximum at ~100 keV/m damaging than Low LET
2. Further increase in LET results in reduction of
RBE 2. Fortunately they are no external
3. LET higher than 100 KeV/ m : Excess dose hazards except for neutrons
deposited in cells (Overkill)

April 6, 2024 Bhabha Atomic Research Centre 12

3. Cell/tissue type and cell division stage
Bergonie and Tribondeau High RS Medium Low RS
Law of radio-sensitivity RS
(RS Law)
• Dividing cells more Dividing cells in Skin Highly
sensitive than non- • Bone marrow Mesoderm differentiated non-
dividing cells organs dividing cells
• GI tract
• Lung • Liver, • Muscle
• Stem cells more • Spleen • Heart • Bones
sensitive than • Thymus • Kidney • Nervous system
differentiated cells • Lymphatic nodes
• Gonads
Cell Cycle stage • Eye lens
• Cells in M phase are Lymphocytes
most sensitive and S- (exception to the RS laws)
phase cells are least
sensitive

• Radio-sensitivity
M>G2>G1>S
 3. Cell/tissue type and cell division stage
Purpose Of cell division

2. Maintenance:
• Replenishment of continuously dying cells
1. Growth: embryo and children • Wound healing
Skin GI tract Blood cells

3. Reproduction Lung epithelium Wound healing

4. Exposure condition
1. Whole body exposures more harmful than localized ones
e.g.,
• LD50/60 for WBD: ~4Gy
• Cancer therapy doses: ~60GY (Localized)

2. Internal contamination are more hazardous than external exposures as

exposure continues till the nuclide is present in the body

5. Presence of absence of chemical modifiers

Radioprotectors: can reduce effect of radiation by quenching the free radicals or

enhanced DNA repair e.g., Amifositne

Radiosensitizers: can enhance the effects of radiation by increasing the reactive

oxygen species or inhibiting repair machinery e.g., Oxygen
Oxygen can enhances low LET radiation effect by 3 times (oxygen enhancement
ratio)
DETERMINISTIC AND STOCHASTIC EFFECTS
DETERMINISTIC 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
 Sure to occur at an adequate dose
exposed
STOCHASTIC EFFECT
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 established at low
Occurs only among a small percentage of those
Deterministic vs. Stochastic Effect
 Acute whole body exposure (low LET radiation)
Dose Range Effect
Less than 0.1 Gy No detectable effects (DNA breaks inside
cells can be observed transiently before
repair)- No symptoms

Above 0.1 Gy Chromosome aberrations detectable

(for biodosimetry)- No symptoms

Above 0.5 Gy Above effect plus transient reduction in

White Blood Cell (lymphocytes &
granulocyte) count – No symptoms
ACUTE radiation Syndromes above >1Gy
Dose Range Effect
1 Gy Radiation Sickness
3-5 Gy Bone-marrow Syndrome
5-15 Gy Gastrointestinal tract Syndrome

>15 Gy Central Nervous System Syndrome

 Acute radiation syndrome(ARS)
• Combination of clinical syndromes occuring in stages hours to weeks
after exposure as injury to various tissues and organs is expressed
Phases of ARS Threats of ARS
1. Accidents at Irradiation facilities
1. Initial or prodromal phase
2. Reactor Incidents
or radiation sickness
3. Transportation Incidents
2. Latent phase
4. Disposal accidents
3. Manifest illness phase
5. Radiological Dispersal Devices/Dirty Bombs
4. Recovery phase 6. Radiological Exposure Devices
7. Nuclear Detonation: Weapons, Improvised
Nuclear Devices
 ACUTE RADIATION SYNDROMES
(whole body exposure)
Time of death
Dose (Gy) Syndrome Organs Affected after exposure
(days)
3-5 Hematopoietic Bone Marrow 30-60
5-15 Gastrointestinal Gastrointestinal 7-20
>15 Tract system <5, dose-
Central Nervous Brain and dependent
muscles System
 Radiation Sickness or Prodromal Syndrome
or NVD Syndrome
• Occurs when whole body exposure is more than 1Gy
• Symptoms:
– Nausea
– Vomiting
– Diarrhea (at doses >5Gy)
– Fatigue
– Headache
– Lack of appetite
• Symptoms start to disappear within 24-48 hours after
exposure
The above symptoms do not confirm radiation exposure, symptoms are general not specific
to radiation
Lymphocyte Kinetics post radiation
exposure
 1. Hematopoietic syndrome
Bone marrow syndrome
• Occurs when whole body is exposed to 3-5 gray.
• Involves loss of bone marrow stem cells which are
progenitors for different cells of blood.
• Symptoms:
– Anemia (Low RBC synthesis)
– Frequent Infections (Low WBC synthesis)
– Fever
– Hemorrhage (Low platelets synthesis)
• Sever symptoms start appearing after 30-60 Days.
• Fatality occurs in 30-60 days of exposure.
 3-5 Gy is also known as LD50/60 which means 50 % mortality
within 60 days after 3-5 Gy of whole body radiation exposure.
Intestinal Lumen
2.GASTROINTESTINAL TRACT SYNDROME
• Occurs when whole body is exposed to ~5-15 Gray.
• It involves damage to actively dividing cells of the
gastrointestinal tract (crypt of epithelial cells present in small
intestine)
• Symptoms:
– Poor absorption of nutrients.
– Bloody Diarrhea leading to fluid loss and electrolyte imbalance in
cells
– Ulceration
– Low blood pressure
– Circulatory collapse
• Symptoms manifest 3-6 days after exposure
• Fatality occurs within 1-2 weeks.
3. CENTRAL NERVOUS SYSTEM SYNDROME

• Occurs when whole body exposure is higher than 15 Gray

• Involves damage to central nervous system.
• Symptoms:
– Coma
– Tremors
– Ataxia (In-voluntary movement)
– Convulsions
– Delirium (talking without senses)
• Symptom onset within few hours of exposure.
• Fatality occurs within 5 days.
 PARTIAL BODY EXPOSURE
1.Skin
– Threshold 3 Gray:
• Transient erythema within 1-2 days.
• Temporary epilation

– Threshold 6 Gray:
• Permanent epilation
• Fixed erythema within 3-4 days

– Threshold 10-20 Gray:

• Burns, skin peeling off, blisters, wounds necrosis.
Occupational radiation burn following approximately
three weeks of exposure to radiation emitted from nested
voltage electron beam accelerator being tested to kill
bacteria.

Radiation injury evolves slowly

 ACUTE PARTIAL BODY EXPOSURES
3. Effects in EYE
Anatomy of eye lens:
THRESHOLD DOSE CONSEQUENCE

0.5 Gy Cataract

Time of appearance several years

(LATE EFFECT)

• Eye lens consists of water and lens fibres (elongated

lens epithelium cells) which are made up of soluble
transparent crystallin proteins
• The crystallin proteins are long lived >50Y
• Clumping of this proteins leads to opacity of the lens
i.e., cataract
• This could be due to trauma, IR, UV and MW, aging,
disease, injury during surgery
• Efficient Treatments are available require minor surgery
 ACUTE PARTIAL BODY EXPOSURES

3.REPRODUCTIVE SYSTEM

MALES THRESHOLD SYMPTOMS

(TESTES) DOSE
0.15Gy Temporary sterility
(after 2 months)
3.5-6 Gy Permanent sterility

FEMALES
(OVARIES) Sterility age dependent
1.5-2 Gy Temporary sterility
2.5-6 Gy Permanent sterility
 Radiation Carcinogenesis
1. Dose response relationship based on epidemiology
2. Assessment of excess cancers
3. Life time risk – Projection model
– Additive, Multiplicative / Relative risk
4. Projection across the populations based on
background incidence of cancer
5. Correction for low-dose, low-dose rate situations
(DDREF = 2)
6. Calculation of age truncated risk (ICRP60)
– 0 – 90 years: 5% Sv-1
– 18 – 65 years: 4% Sv-1
 Tissue weighting factors ICRP2007
Tissue WT  WT
Bone marrow (red), Colon, Lung, 0.12 0.60
Stomach, Breast
Gonads 0.08 0.08

Bladder, Oesophagus, Liver, Thyroid 0.04 0.16

Bone surface, Brain, Salivary glands, 0.01 0.04

Skin.
Remainder Tissues* 0.12 0.12
(Nominal WT applied to the average
dose to 13 tissues)
Total 1 1

* Adrenals, extrathoracic region, gall bladder, heart, kidneys, lymphatic

nodes, muscle, oral mucosa, pancreas, prostate (males), small intestine,
 Components of detriment
•Prevalence
•Curability
•Lost life span
•Lethality &Quality of life with particular cancer
type
 Fetal Radiation Risk
• There are radiation-related risks throughout
pregnancy which are related to the stage of
pregnancy and absorbed dose
• Radiation risks are most significant during
organogenesis and in the early fetal period
somewhat less in the 2nd trimester and least in the
third trimester

Most
risk Less Least
Incidence of Prenatal & Neonatal Death
and Abnormalities
 Effects on Embryo and Fetus
Age Threshold for Threshold for
lethal effects malformations
(mGy) (mGy)
1 day 100 No effect

14 days 250 -

18 days 500 250

20 days >500 250

50 days >1000 500

50 days to >1000 >500

birth
Approximate fetal doses from conventional X
Ray examinations

Mean ( mGy ) Maxi mum ( mGy )

Abdo men 1.4 4.2

Chest <0.01 <0.01

Intravenous 1.7 10
urogram or
lumbar spine
Pelvis 1.1 4

Skull or <0.01 <0.01

thoracic spine
 Genetic Effects and Genetic Risks
• Ionizing radiation is known to cause heritable mutations in plants and
animals
However,
• intensive studies of 70,000 offspring of the atomic bomb survivors have
failed to identify an increase in congenital anomalies, cancer,
chromosome aberrations in circulating lymphocytes or mutational blood
protein changes.
• ICRP 60 1990:
– Genetic risk = 0.6% per Sv for working population.
– 1% per Sv. for general public

• ICRP 2007:
– 0.1% per Sv for working population
– 0.2% per Sv for public
 Examples
Autosomal dominant
Achondroplasia, Huntington’s corea, Dupuytren’s contracture, polydactyly, Retinoblastoma.

Sex-linked (X-linked)
Haemophilia A, Muscular dystrophy-Duchenne, Ichthyosis, Hypogammaglobinaemia,
Agammaglobinaemia and colour blindness, Lesch-Nyhan Syndrome.

Recessive diseases
Phenylketonuria, Sickle cell anaemia, Albinism, Cystic fibrosis, Deafness and several metabolic
disorders, Tay Sach’s disease.

Chromosomal disorders
Numerical: Down’s syndrome(21T), Edward syndrome(18T), Pateau syndrome(13T), Kline-Felter’s
syndrome(XXY), Turner’s syndrome(X0), Triple X and supermale (XYY), Cri du chat (structural DEL in
5).

Congenital malformations
Spinabifida, Hydrocephalus, Cataracts, Strabismus, Septal defects of the heart, cleft lip and palate,
Club feet and hand, Congenital dislocation of hips.

Multifactorial
Diabetes, Mental retardation, Epilepsy, Schizophrenia and Myopia.
 Key Points
 Stochastic effects: probabilistic in nature may or may not occur. Cancer & genetic effects
 Deterministic effects: Certain to happen after a dose threshold is crossed. e.g., all acute Radiation syndromes,
Burns etc.

 Acute effects: Symptoms appear within days to months. Acute Radiation Syndromes and partial body effects.
e.g., all the deterministic effects except cataract
 Late effects: Appear years to decade after exposure. Cancer and hereditary effects, Cataract

 Somatic Effects: Occur in the persons’ body who is exposed.

 Genetic effects: Occur in the children of exposed person.
 In-utero Effect: Effect in the child exposed in womb (Also a kind of somatic effect).

 Cancer risk:~4.7 % & 5% per Sv for occupational workers and public respectively
 Genetic risk: 0.1 & 0.2% per Sv for occupational workers and public respectively

 Dicentrics assay for exposures above 0.1Gy

 Threshold for temporary sterility in males ~150mGy
 Threshold for reduction in blood cell count: ~0.5Gy
 Threshold for NVD:~1Gy
 Threshold for radiation burns ~10Gy
 Most
specific

Ref: IAEA Guidelines on medical management of radiation injuries, safety series 101, 2020
Ref: IAEA Guidelines on medical management of radiation injuries, safety series 101, 2020
 Sources of Data
Population Approximate Size
Atomic bomb survivors Japan: 86 000
Atomic tests:Semipalatinsk/Altai 30 000
Marshallese islanders 2 800
Nuclear accidents: intervention teams Chernobyl (total) > 200 000
population Chernobyl (>185 kBq /m2 137Cs) 1 500 000
population Chelyabinsk (total) 70 000
Medical procedures:
low LET iodine treatment and therapy ~ 70 000
chest fluoroscopy 64 000
children hemangioma treatment 14 000
high LET thorotrast angiography 4 200
Ra-224 treatment 2 800
Prenatal exposure (fetal radiography, atomic bombs) 6 000
Occupational exposure: workers nuclear industry (Japan, UK) 115 000
uranium miners 21 000
radium dial painters 2 500
radiologists 10 000
Natural exposure (Chinese, EC and US studies) several 100 000
IAEA Documentation
Thank You !
 Difference between damage by non-ionizing and
ionizing radiation

Non-ionizing radiations:
1. Low energy partials: Energy <10eV
2. Cause damage at high intensity
3. Mechanism:
• Heat generation due to molecular
vibration (IR)
• Molecular torsion (MW)
• Photochemical reaction (UV)
4. Damaging effects
• Fire burn
• Blindness Ref: http://hyperphysics.phy-astr.gsu.edu/hbase/mod3.html#c3
• Photochemical burns due to lasers
• Sunburns
 Ionizing radiation

Body
Systems
Organs
Tissues Biological Effects

Cells
Bio-molecules
• X-rays and gamma rays: no physical difference
Atoms • Origin is different
• High energy X-rays are also generated these days
Radiation Damage
• for different purpose
(Ionization)
• Although a radiation can be ionizing if photon energy Ionization energies:
>10eV • Oxygen and hydrogen: ~14eV
• Most abundant atoms in our body H,O, C and N most of • Carbon: ~11MeV
the atoms are incorporated in biomolecules and most
• Nitrogen: ~ 14MeV
abundant molecule is H2O
• Ionization of water requires ≥34KeV
• H2O: 33 eV
 Radiation induces chain reaction of lipid peroxidation

Lipids have high turnover rates for e.g., 50% of total

phospholipids are replaced within one or two cell
divisions. The rate may vary from tissue to tissue
however it ranges few days to months overall.
 Protein damage is also detected after radiation
exposure

• Radiation can create break in the backbone of peptide.

• It can modify amino acids of the proteins and hence affect conformation and function of the
same. e.g., carbonylation, desulphurization of amino acids.

• Expression levels of a number of proteins are altered post radiation exposure.

• Most of the proteins have high turnover rates hence, get replenished with new ones within
hours to days.

• However proteins such as collagen, eye lens crystallin have life more than 50years. Damage
Genetic codes and gene expression

• All the cells carry same 46 DNA molecules

• Overall there are ~30000 genes on our DNA
• Not all the genes are active in all the cells
• Cells get specialized as an embryo develops into grown individual
• Some genes express in all the cells while specific genes express in specific cell type
1. The genetic code is written in linear form, using as “letters” the ribonucleotide bases that compose mRNA molecules.
The ribonucleotide sequence is derived from the complementary nucleotide bases in DNA.
2. Each “word” within the mRNA consists of three ribonucleotide letters, thus referred to as a triplet code. With several
exceptions, each group of three ribonucleotides, called a codon, specifies one amino acid.
3. The code is unambiguous—each triplet specifies only a single amino acid.
4. The code is degenerate, meaning that a given amino acid can be specified by more than one triplet codon. This is the
case for 18 of the 20 amino acids.
5. The code contains one“start”and three“stop”signals,trip- lets that initiate and terminate translation, respectively.
6. No internal punctuation (analogous, for example, to a comma) is used in the code. Thus, the code is said to be
commaless. Once translation of mRNA begins, the codons are read one after the other with no breaks be- tween them (until
a stop signal is reached).
7. The code is nonoverlapping. After translation com- mences, any single ribonucleotide within the mRNA is part of only
one triplet.
8. The sequence of codons in a gene is colinear, with the sequence of amino acids making up the encoded protein.
9. The code is nearly universal. With only minor exceptions, a single coding dictionary is used by almost all viruses,
prokaryotes, archaea, and eukaryotes.

One code one aa,

4 3=64
Codes 20 AAs one aa many codes