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RADIATION BIOLOGY

Radiation biology is the study of the effects of ionizing radiation on living systems. The initial interaction between ionizing radiation and matter occurs at the level of the electron within the first 10-13 second after exposure. These changes result in modification of biologic molecules within the ensuing seconds to hours.

In turn, the molecular changes may lead to alterations in cells and organisms that persist for hours, decades, and possibly even generations. If enough cells are killed in an individual, it may cause injury or death. If cells are modified, such changes may lead to cancer or disorders in the descendents of the exposed individual.

DETERMINISTIC EFFECTS
Deterministic effects are those effects in which the severity of response is proportional to the dose. These effects, usually cell killing, occur in all people 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.

STOCHASTIC EFFECTS
Stochastic effects are those for which the probability of the occurrence of change, rather than its severity is dose dependent. Stochastic effects are all or none: a person either has or does not have the condition. There is no dose threshold. Eg. Radiation induced cancer is a stochastic effect because of greater exposure of a person or population to radiation but not its severity.

RADIATION DAMAGE TO BIOLOGICAL TISSUES


Two theories: 1. DIRECT EFFECT OR TARGET ACTION THEORY 2. INDIRECT EFFECT OR POISON CHEMICAL THEORY.

DIRECT EFFECT OR TARGET ACTION 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

INDIRECT EFFECT OR POISON CHEMICAL THEORY


Indirect effect (Poison chemical theory) of radiation injury suggests that x-ray photons are absorbed within the cell and cause the formation of toxins, which damage the cell. indirect injuries from exposure to ionizing radiation occur frequently because of the high water content of cells.

chances of free radical formation and indirect injury are great because cells are 70% to 80% water

RADIOLYSIS OF WATER

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).

CHANGES IN BIOLOGIC MOLECULES


Nucleic Acids Radation produces different types of alteration in DNA: 1)change or loss of a base. 2)disruption of hydrogen bonds between DNA strands 3)breakage of one or both DNA strands 4) cross linking of DNA strands within the helix, to other DNA strands or to proteins.

Proteins 1) changes in their secondary and tertiary structures 2)through disruption of side chains or the breakage of hydrogen or disulphide bonds 3)induce changes in intermolecular and intramolecular crosslinking.

Radiation effects at the cellular level


Nucleus 1)nucleus is more radiosensitive than the cytoplasm, especially in dividing cells.

2)The sensitive site in the nucleus is the DNA within chromosomes.

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 the time of mitosis when the DNA condenses to form chromosomes.

The type of damage that may be observed depends on stage of cell cycle at the time of irradiation. If radiation exposure occurs after DNA synthesis only one arm of affected chromosome is broken if the radiation induced break occurs before the DNA has replicated the damage manifests as break in both the arms at the next mitosis.

Cytoplasm
After large doses of radiation, mitochondria demonstrate:1) increased permeability, 2) swelling 3) disorganisation of the internal cristae.

LAW" OF BERGONIE' AND TRIBONDEAU Radiation has a more rapid (is more effective) effect against cell that are actively 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 reproduce to replace themselves and to provide cells which mature into more differentiated cells.

CLASSIFICATION
Rubin and Casarett classification of cellular populations based on reproductive kinetics: These classifications cells is an attempt to explain the difference in observed cellular and tissue radiosensitivity based on the reproductive and functional characteristics of various cell lines.

Vegetative Intermitotic Cells (VIM)


Most radio sensitive They divide regularly, have long mitotic futures and do not undergo differentiation between mitosis. Examples are erythroblasts, intestinal crypt cells and basal cells of the skin. Essentially continuously repopulated throughout life.

Differentiating Intermitotic Cells (DIM)


Less radiosensitive. They divide regularly although they undergo some differentiation between mitosis. Spermatogonia are a prime example , inner enamel epithelium of developing teeth Have substantial reproductive capability but will eventually stop dividing or mature into a differentiated cell line

Multipotential Connective Tissue Cells


Cells which divide at irregular intervals often in response to a need. Relatively long cell life cycle. Major examples are fibroblasts although recently more examples of such cells have been identified in a number of tissues

Reverting Postmitotic Cells (RPM)


does not normally undergo division but can do so if called upon by the body to replace a lost cell population. These are generally long lived cells. Mature liver cells, pulmonary cells and kidney cells make are examples of this type of cell.

Fixed Postmitotic Cells. (FPM)


These cells do not and cannot divide. They are highly differentiated and are highly specialized in there morphology and function. May be very long lived or relatively short lived but replaced by differentiating cells below them in the cell maturation lines. Examples are: Neurons, muscle cells and RBCs, straited muscle.

RADIATION EFFECTS AT THE TISSUE AND ORGAN LEVEL


SHORT TERM EFFECTS 1) determined primarily by the sensitivity of its parenchymal cells. 2) The extent of cell loss depends on damage to stem cell pools and proliferative rates of the cell population. 3) eg; bone marrow, oral mucous membrane 4) cells that rarely or never divide (eg; muscle) demonstrate little or no radiation induced hypolasia over the short term.

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 slow progressive fibrosis around the vessels 4) premature narrowing and eventual obliteration of vascular lumens. 5) impairs in transport of the oxygen nutrients and waste products and result in death of all cell types

RELATIVE RADIO SENSITIVITY OF VARIOUS ORGANS


HIGH Lymphoid organs Bone marrow Testes Intestine Mucous membrane INTERMEDIATE Fine vasculature Growing cartilage Growing bone Salivary glands lungs, kidney, liver LOW Optic lens Mature erythrocytes Muscle cells Neurons

RADIATION EFFECT ON ORAL TISSUES


Oral Mucous Membrane

Xerostomia

Radiation Caries

Bone

Dentofacial Abnormalities

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 onset and the greater the severity of symptoms.

Latent period 1) no signs or symptoms of radiation sickness 2) hours or days at supralethal( greater than 5 gy) exposure to a few weeks at sublethal( less than 2 Gy) exposures.

Hematopoetic syndrome 1) Whole body exposure of 2 to 7 cause injury to the hematopoetic stem cells of the bone marrow and spleen 2) The mature circulating granulocytes, platelets and erythrocytes themselves are very radio resistant 3) Their paucity in the peripheral blood after irradiation reflects the radio- sensitivity of their precursors. 4) infection ,hemorrhage and anemia. When death occurs ,it usually appear 10 to 30 days.

Gastrointestinal syndrome 1) Whole body exposure in the range of 7 to 15 Gy cause extensive damage to the gastrointestinal system. 2) This damage, in addition to the hematopoetic damage, causes signs and symptoms called gastrointestinal syndrome. 3) second through about fifth day no symptoms are present. 4) injury to the rapidly proliferating basal epithelial cells of the intestinal villi and leads to loss of the intestinal mucosa.

5) the diarrhea, dehydration and loss of weight that are observed. 6) Endogenous intestinal bacteria readily invade the denuded surface, producing septicemia

Cardiovascular and Central Nervous System Syndrome 1) Exposure in excess of 50 Gy usually cause death in 1 to 2 days 2) showed collapse of the circulatory system with a precipitate fall in blood pressure in the hours preceding death. 3) Autopsy shows necrosis of cardiac muscle 4) intermittent stupor, incordination, disorientation and convulsions suggestive of extensive damage to the nervous system. 5) clinical course may run from only a few minutes to about 48 hours before death occurs.

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,