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RADIATION BIOLOGY
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Radiation biology is the study of the
effects of ionizing radiation on livingsystems.
The initial interaction between ionizing
radiation and matter occurs at the level ofthe electron within the first 10-13 secondafter exposure.
These changes result in modification ofbiologic molecules within the ensuingseconds to hours.
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In turn, the molecular changes may lead
to alterations in cells and organisms thatpersist for hours, decades, and possiblyeven generations.
If enoughcells are killed in an individual,it may cause injury or death.
If cells are modified, such changes may
lead to cancer or disorders in thedescendents of the exposed individual.
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DETERMINISTIC EFFECTS
Deterministic effects are those effects inwhich the severity of response isproportional to the dose.
These effects, usually cell killing, occur in allpeople when the dose is large enough.
Deterministic effects have a dose threshold
below which the response is not seen. Examples of deterministic effects include
oral changes after radiation therapy.
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STOCHASTIC EFFECTS
Stochastic effects are those for which theprobability of the occurrence of change,rather than its severity is dose dependent.
Stochastic effects are all or none: a personeither has or does not have the condition.
There is no dose threshold.
Eg. Radiation induced cancer is a stochasticeffect because of greater exposure of aperson or population to radiation but not itsseverity.
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RADIATION DAMAGE TOBIOLOGICAL TISSUES
Two theories:
1. DIRECT EFFECT OR TARGET
ACTION THEORY
2. INDIRECT EFFECT OR POISON
CHEMICAL THEORY.
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DIRECT EFFECT OR TARGETACTION THEORY
A critical target is ionized
This target is DNA
Free radical production
(R: biological molecule,H: hydrogen atom)RH + x-radiationR. + H+ e
Free radical fates:
1) Dissociation:
R. X + Y.
2) Cross linking:
R. + S.RS
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INDIRECT EFFECT OR POISONCHEMICAL THEORY
Indirect effect (Poison chemical theory) ofradiation injury suggests that x-rayphotons are absorbed within the cell andcause the formation of toxins, whichdamage the cell.
indirect injuries from exposure to ionizingradiation occur frequently because of thehigh water content of cells.
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chances of free radical formation andindirect injury are great because cells are70% to 80% water
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RADIOLYSIS OF WATER
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Cell Cycle and Cell Death
Most radiosensitive phases: M, G2,
Most radioresistant phase: S,
Checkpoints: G1/S, intra-S, G2/M,
DNA damage: cell cycle arrest repair or loss of function (diff.cells), loss of reproductive integrity (stem cells).
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CHANGES IN BIOLOGICMOLECULES
Nucleic Acids
Radation produces different types
of alteration in DNA:1)change or loss of a base.
2)disruption of hydrogen bonds between DNA
strands3)breakage of one or both DNA strands
4) cross linking of DNA strands within thehelix, to other DNA strands or to proteins.
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Proteins
1) changes in their secondary andtertiary structures
2)through disruption of side chains orthe breakage of hydrogen ordisulphide bonds
3)induce changes in intermolecular andintramolecular crosslinking.
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Radiation effects at the cellularlevel
Nucleus1)nucleus is more radiosensitive than
the cytoplasm, especially
in dividing cells.
2)The sensitive site in the nucleus is theDNA within chromosomes.
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Chromosome aberrations
1) serves as useful marker for radiation
injury.2) They may be easily visualised and
quantified and the extent of their
damage is related to cell survival.3) observed in irradiated cells at thetime of mitosis when the DNAcondenses to form chromosomes.
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The type of damage that may beobserved depends on stage of cell cycleat the time of irradiation.
If radiation exposure occurs after DNAsynthesis only one arm ofaffected chromosome is brokenif the radiation induced break
occurs before the DNAhas replicated the damagemanifests as break in boththe arms at the
next mitosis.
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Cytoplasm
After large doses of radiation,
mitochondria demonstrate:-
1) increased permeability,
2) swelling
3) disorganisation of the internal cristae.
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LAW" OF BERGONIE' ANDTRIBONDEAU
Radiation has a more rapid (is moreeffective) effect against cell that areactively dividing, are undifferentiated and
have a large dividing future. Undifferentiated cells are precursor or
stem cells and have less specialized
functions. Their major role is to reproduceto replace themselves and to provide cellswhich mature into more differentiatedcells.
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CLASSIFICATION
Rubin and Casarett
classification of cellular populations
based on reproductive kinetics:
These classifications cells is anattempt to explain the difference inobserved cellular and tissueradiosensitivity based on the
reproductive and functionalcharacteristics of various cell lines.
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Vegetative Intermitotic Cells (VIM)
Most radio sensitive
They divide regularly, have long mitoticfutures and do not undergo differentiation
between mitosis. Examples areerythroblasts, intestinal crypt cells andbasal cells of the skin.
Essentially continuously repopulatedthroughout life.
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Differentiating Intermitotic Cells (DIM)
Less radiosensitive. They divide regularlyalthough they undergo some differentiationbetween mitosis. Spermatogonia are a
prime example , inner enamel epithelium ofdeveloping teeth
Have substantial reproductive capability but
will eventually stop dividing or mature into adifferentiated cell line
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Multipotential ConnectiveTissue Cells
Cells which divide at irregular intervalsoften in response to a need.Relatively long cell life cycle.
Major examples are fibroblastsalthough recently more examples ofsuch cells have been identified in anumber of tissues
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Reverting Postmitotic Cells (RPM)
does not normally undergo divisionbut can do so if called upon by thebody to replace a lost cell population.
These are generally long lived cells.
Mature liver cells, pulmonary cells andkidney cells make are examples ofthis type of cell.
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Fixed Postmitotic Cells. (FPM)
These cells do not and cannot divide.
They are highly differentiated and arehighly specialized in there morphology
and function. May be very long lived or relatively
short lived but replaced by
differentiating cells below them in thecell maturation lines.
Examples are: Neurons, muscle cellsand RBCs, straited muscle.
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RADIATION EFFECTS AT THE TISSUEAND ORGAN LEVEL
SHORT TERM EFFECTS
1) determined primarily by the sensitivity of itsparenchymal cells.
2) The extent of cell loss depends on damage tostem cell pools and proliferative rates of the cellpopulation.
3) eg; bone marrow, oral mucous membrane
4) cells that rarely or never divide (eg; muscle)demonstrate little or no radiation inducedhypolasia over the short term.
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LONG TERM EFFECTS
1) depend on extent of damage to the fine
vasculature.2) Irradiation of capillaries causes swelling,
degeneration and necrosis.
3) increase permeability and initiate a slowprogressive fibrosis around the vessels
4) premature narrowing and eventual obliterationof vascular lumens.
5) impairs in transport of the oxygen nutrients andwaste products and result in death of all celltypes
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RELATIVE RADIO SENSITIVITYOF VARIOUS ORGANS
HIGH INTERMEDIATE LOW
Lymphoid organs Fine vasculature Optic lens
Bone marrow Growing cartilage Mature erythrocytes
Testes Growing bone Muscle cells
Intestine Salivary glands Neurons
Mucous membrane lungs, kidney, liver
RADIATION EFFECT ON ORAL
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RADIATION EFFECT ON ORALTISSUES
Oral Mucous Membrane
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Xerostomia
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Radiation Caries
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Bone
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Dentofacial Abnormalities
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ACUTE RADIATION SYNDROME
Prodromal period
1) first minutes to hours :-about 1.5 Gy
2) anorexia nausea vomiting, diarrhoea,weakness and fatigue
3) involve autonomic nervous system
4) The higher the dose more rapid the onsetand the greater the severity of symptoms.
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Latent period
1) no signs or symptoms of radiationsickness
2) hours or days at supralethal( greaterthan 5 gy) exposure to a few weeksat sublethal( less than 2 Gy)exposures.
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Hematopoetic syndrome
1) Whole body exposure of 2 to 7 cause injury to
the hematopoetic stem cells of the bone marrowand spleen
2) The mature circulating granulocytes, plateletsand erythrocytes themselves are very radio
resistant
3) Their paucity in the peripheral blood afterirradiation reflects the radio- sensitivity of their
precursors.4) infection ,hemorrhage and anemia. When death
occurs ,it usually appear 10 to 30 days.
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Gastrointestinal syndrome
1) Whole body exposure in the range of 7 to 15 Gy
cause extensive damage to the gastrointestinalsystem.
2) This damage, in addition to the hematopoeticdamage, causes signs and symptoms called
gastrointestinal syndrome.
3) second through about fifth day no symptoms arepresent.
4) injury to the rapidly proliferating basal epithelialcells of the intestinal villi and leads to loss of theintestinal mucosa.
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5) the diarrhea, dehydration and loss ofweight that are observed.
6) Endogenous intestinal bacteriareadily invade the denuded surface,producing septicemia
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Cardiovascular and Central Nervous SystemSyndrome
1) Exposure in excess of 50 Gy usually cause deathin 1 to 2 days
2) showed collapse of the circulatory system with aprecipitate fall in blood pressure in the hours
preceding death.3) Autopsy shows necrosis of cardiac muscle
4) intermittent stupor, incordination, disorientationand convulsions suggestive of extensive damageto the nervous system.
5) clinical course may run from only a few minutes toabout 48 hours before death occurs.
RADIATION EFFECTS ON
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RADIATION EFFECTS ON
EMBROYS AND FETUSES
Development Stages
Pre-implantation (day 1 to 10):
vulnerable embrionic cells with high repair capacity,
all or nothing effect (prenatal death or full
recovery), no retardation at birth
Organogenesis (day 11 to 42):
permanent growth retardation,
impaired organogenesis, neonatal death
Growth stage (day 43 to birth):
growth retardaton,