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Radiation Biology
Danish Hamid
3rd prof
CONTENTS
• Introduction
• Interaction of radiation with biological
molecules
• Radiation effects at cellular level
• Types of biologic effects of Radiation
• Radiosensitivity
INTRODUCTION
• Radiation biology is the study of the effects of
ionising radiation on living systems.
• It is also defined as the study of the biological
effect of radiation caused mainly by ionisation
of water molecules within cells which produce
highly reactive free radicals which, in turn,
damage macromolecules ,such as DNA.
Interaction of radiation with biological
molecules
Biological effect of radiation occurs through;
a) Direct action, or
b) Indirect action
Direct action
• Also called Target action theory
• X-ray radiation directly interacts and ionizes a
biologic macromolecule (DNA) and forms
unstable free radicals.
• These free radicals quickly re-form into stable
configurations by dissociation or cross-linking.
.
• X-ray radiation + RH = R.
+ H+ + e-
• Dissociation: R.
= X + Y .
• Cross-linking: R.
+ S.
= RS
• The altered biologic molecules differ
structurally and functionally from original
molecules, this will lead to biologic change.
Indirect action
• Also called Poison chemical theory
• X-ray radiation interacts and ionizes the
cellular water releasing highly reactive
radiolytic products, which in turn, react with
cellular DNA causing biologic change.
Fig: Radiolysis of water
.
• X-ray radiation + H2O = H.
+ OH.
• R – H + OH.
= R .
+ H2O
• R – H + H.
= R.
+ H2
In the presence of oxygen, hydroperoxyl and
hydrogen peroxide are formed – these are
strong oxidizing agents that contribute
significantly to indirect actions.
• H.
+ O2 = HO2
.
• HO2
.
+ HO2
.
= H2O2 + O2
Radiation effects at cellular level
 Nucleic acids
– Breakage of one or both strands of DNA
– DNA-DNA or DNA-proteins cross-linking
– change or loss of base
– disruption of hydrogen bonds between the DNA
strands
 Proteins
– Denaturation
– Inter and intra-molecular cross-linking
– Disruption of secondary and tertiary structure
 Chromosomal Aberrancy
–Chromosome aberration is observed in
irradiated cells at the time of mitosis when
DNA condenses to form chromosomes
–Type of damage depends on cell cycle at the
time of irradiation
• Radiation in G2 or mid and late S phases: If
radiation exposure occurs after DNA synthesis,
only one arm of the affected chromosome is
broken, and it is called chromatid aberration
• Radiation in G1 or early S phase: If radiation
exposure occurs before the DNA synthesis, then both
arms of the chromosome will be broken, and it is
called chromosome aberration
• Chromosome effect could include inability to pass
information, abnormal replication, cell death, etc.
Chromosome aberrations can occur due to incorrect
repairs, such as ring formation, dicentric formation,
translocation and tetracentric exchange
 Intracellular
• Nucleus – most sensitive, inhibition of cell
division
• Cytoplasm – Increased permeability to Na and
K ions, swelling and disorganization of
mitochondria, focal cytoplasmic necrosis
• Telomerase is produced – cell becomes
immortal
 Cell replication
• Radiation causes damage to cell systems
either by
–Mitotic delay (delay in cellular progression
through cell cycle) or
–Reproductive cell death
• DNA damage
• Bystander effect
• Recovery
Types of biologic effects of Radiation
BIOLOGIC
EFFECT
Somatic
Stochastic
effect
Deterministic
effect
Genetic
Stochastic effect
• Caused by sub-lethal DNA damage
• There is no minimal threshold level. Effect can
occur by any dose of radiation.
• Severity of effect is independent of dose; ‘ALL OR
NONE’ response – an individual either manifests
effect or does not
• Probability of occurrence of effect is dose
dependent.
• Also seen in diagnostic maxillofacial radiology
• Example: Leukemia, certain cancers
Deterministic effect
• Caused by lethal DNA damage causing cell death
• Effect occurs only when threshold dose is
exceeded
• Severity of clinical effects is dependent on dose
of radiation
• Probability of effect is independent of dose
• Not encountered in diagnostic radiology
• Example: Mucositis, Cataract, Osteoradionecrosis
Radiosensitivity
• It is defined as the ability of radiations to
biologically change cells or tissues.
• Cells that divide rapidly are more radiosensitive
than those which do not divide frequently.
• Tissues or cells that are least sensitive to
radiation are called radioresistant tissues or
cells
• Tissues or cells which are more sensitive to
radiation are known as radiosensitive tissues or
cells
Radiosensitivity of organs
High Intermediate Low
Lymphoid organs Fine vasculature Optic lens
Bone marrow Growing cartilage Mature erythrocytes
Testes Growing bone Muscle cells
Intestine Salivary gland Neurons
Mucous membrane Lungs
Kidney
Liver
RADIOSENSITIVITY OF THE CELLS
• The cells having;
– high mitotic rate,
– less differentiated and
– high cellular metabolism
are most radiosensitive.
• Since malignant tumours and cancers have
highly dividing cells, they are more sensitive to
radiation and hence are treated with
radiotherapy
Casarett’s categorization of cell types by
radiosensitivity
Radiosensitivity Category Cell division Differentiation
status
Examples
High Vegetative
intermitotic
Rapid Undifferentiated Basal cells of oral
mucosa,
Erythroblasts
Relatively
radiosensitive
Differentiating
intermitotic
Regular Some
differentiation
Myelocytes,
Spermatocytes
Intermediate Multipotent CT Irregular Fibroblasts,
Endothelial cells
Generally
radioresistant
Reverting
postmitotic
Not regular,
but can be
stimulated to
divide
Fully
differentiated
Hepatocytes
Low Fixed
postmitotic
No Highly
differentiated
Neuron , Muscle
cells

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Radiation biology

  • 2. CONTENTS • Introduction • Interaction of radiation with biological molecules • Radiation effects at cellular level • Types of biologic effects of Radiation • Radiosensitivity
  • 3. INTRODUCTION • Radiation biology is the study of the effects of ionising radiation on living systems. • It is also defined as the study of the biological effect of radiation caused mainly by ionisation of water molecules within cells which produce highly reactive free radicals which, in turn, damage macromolecules ,such as DNA.
  • 4. Interaction of radiation with biological molecules Biological effect of radiation occurs through; a) Direct action, or b) Indirect action
  • 5. Direct action • Also called Target action theory • X-ray radiation directly interacts and ionizes a biologic macromolecule (DNA) and forms unstable free radicals. • These free radicals quickly re-form into stable configurations by dissociation or cross-linking.
  • 6. . • X-ray radiation + RH = R. + H+ + e- • Dissociation: R. = X + Y . • Cross-linking: R. + S. = RS • The altered biologic molecules differ structurally and functionally from original molecules, this will lead to biologic change.
  • 7. Indirect action • Also called Poison chemical theory • X-ray radiation interacts and ionizes the cellular water releasing highly reactive radiolytic products, which in turn, react with cellular DNA causing biologic change. Fig: Radiolysis of water
  • 8. . • X-ray radiation + H2O = H. + OH. • R – H + OH. = R . + H2O • R – H + H. = R. + H2 In the presence of oxygen, hydroperoxyl and hydrogen peroxide are formed – these are strong oxidizing agents that contribute significantly to indirect actions. • H. + O2 = HO2 . • HO2 . + HO2 . = H2O2 + O2
  • 9.
  • 10. Radiation effects at cellular level  Nucleic acids – Breakage of one or both strands of DNA – DNA-DNA or DNA-proteins cross-linking – change or loss of base – disruption of hydrogen bonds between the DNA strands  Proteins – Denaturation – Inter and intra-molecular cross-linking – Disruption of secondary and tertiary structure
  • 11.  Chromosomal Aberrancy –Chromosome aberration is observed in irradiated cells at the time of mitosis when DNA condenses to form chromosomes –Type of damage depends on cell cycle at the time of irradiation • Radiation in G2 or mid and late S phases: If radiation exposure occurs after DNA synthesis, only one arm of the affected chromosome is broken, and it is called chromatid aberration
  • 12. • Radiation in G1 or early S phase: If radiation exposure occurs before the DNA synthesis, then both arms of the chromosome will be broken, and it is called chromosome aberration
  • 13. • Chromosome effect could include inability to pass information, abnormal replication, cell death, etc. Chromosome aberrations can occur due to incorrect repairs, such as ring formation, dicentric formation, translocation and tetracentric exchange
  • 14.  Intracellular • Nucleus – most sensitive, inhibition of cell division • Cytoplasm – Increased permeability to Na and K ions, swelling and disorganization of mitochondria, focal cytoplasmic necrosis • Telomerase is produced – cell becomes immortal
  • 15.  Cell replication • Radiation causes damage to cell systems either by –Mitotic delay (delay in cellular progression through cell cycle) or –Reproductive cell death • DNA damage • Bystander effect • Recovery
  • 16. Types of biologic effects of Radiation BIOLOGIC EFFECT Somatic Stochastic effect Deterministic effect Genetic
  • 17. Stochastic effect • Caused by sub-lethal DNA damage • There is no minimal threshold level. Effect can occur by any dose of radiation. • Severity of effect is independent of dose; ‘ALL OR NONE’ response – an individual either manifests effect or does not • Probability of occurrence of effect is dose dependent. • Also seen in diagnostic maxillofacial radiology • Example: Leukemia, certain cancers
  • 18. Deterministic effect • Caused by lethal DNA damage causing cell death • Effect occurs only when threshold dose is exceeded • Severity of clinical effects is dependent on dose of radiation • Probability of effect is independent of dose • Not encountered in diagnostic radiology • Example: Mucositis, Cataract, Osteoradionecrosis
  • 19.
  • 20. Radiosensitivity • It is defined as the ability of radiations to biologically change cells or tissues. • Cells that divide rapidly are more radiosensitive than those which do not divide frequently. • Tissues or cells that are least sensitive to radiation are called radioresistant tissues or cells • Tissues or cells which are more sensitive to radiation are known as radiosensitive tissues or cells
  • 21. Radiosensitivity of organs High Intermediate Low Lymphoid organs Fine vasculature Optic lens Bone marrow Growing cartilage Mature erythrocytes Testes Growing bone Muscle cells Intestine Salivary gland Neurons Mucous membrane Lungs Kidney Liver
  • 22. RADIOSENSITIVITY OF THE CELLS • The cells having; – high mitotic rate, – less differentiated and – high cellular metabolism are most radiosensitive. • Since malignant tumours and cancers have highly dividing cells, they are more sensitive to radiation and hence are treated with radiotherapy
  • 23. Casarett’s categorization of cell types by radiosensitivity Radiosensitivity Category Cell division Differentiation status Examples High Vegetative intermitotic Rapid Undifferentiated Basal cells of oral mucosa, Erythroblasts Relatively radiosensitive Differentiating intermitotic Regular Some differentiation Myelocytes, Spermatocytes Intermediate Multipotent CT Irregular Fibroblasts, Endothelial cells Generally radioresistant Reverting postmitotic Not regular, but can be stimulated to divide Fully differentiated Hepatocytes Low Fixed postmitotic No Highly differentiated Neuron , Muscle cells