radiation biology lecture

8/3/2019 Radiation Biology Lecture

1/39

RADIATION BIOLOGY


2/39

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.


3/39

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.


4/39

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.


5/39

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.


6/39

RADIATION DAMAGE TOBIOLOGICAL TISSUES

Two theories:

1. DIRECT EFFECT OR TARGET

ACTION THEORY

2. INDIRECT EFFECT OR POISON

CHEMICAL THEORY.


7/39

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


8/39

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.


9/39

chances of free radical formation andindirect injury are great because cells are70% to 80% water


10/39

RADIOLYSIS OF WATER


11/39

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).


12/39

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.


13/39

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.


14/39

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.


15/39

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.


16/39

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.


17/39

Cytoplasm

After large doses of radiation,

mitochondria demonstrate:-

1) increased permeability,

2) swelling

3) disorganisation of the internal cristae.


18/39

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.


19/39

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.


20/39

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.


21/39

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


22/39

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


23/39

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.


24/39

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.


25/39

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.


26/39

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


27/39

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


28/39

RADIATION EFFECT ON ORALTISSUES

Oral Mucous Membrane


29/39

Xerostomia


30/39

Radiation Caries


31/39

Bone


32/39

Dentofacial Abnormalities


33/39

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.


34/39

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.


35/39

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.


36/39

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.


37/39

5) the diarrhea, dehydration and loss ofweight that are observed.

6) Endogenous intestinal bacteriareadily invade the denuded surface,producing septicemia


38/39

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


39/39

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,

radiation biology lecture

Documents