Radiobiology

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Fast moving electrons transfer energy to water and cellular molecules in discrete events whose average energy is

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called a spur and involves 60 eV of energy transfer

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Concerning the effects of ionizing radiation on DNA

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double strand breaks are produced at <5% of the frequency of single strand breaks at all doses of radiation

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The biological effects of radiation are dependent upon

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total dose, dose rate, and radiation quality

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Processes affected by the presence of oxygen

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both direct and indirect action

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Direct effects

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ionizations produced directly by energy depositions in macromolecules

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indirect effects

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ionizations of mainly water molecules and production of diffusible free radicals

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radiations in order of increasing LET

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20 Mev photons, 200 keV photons, 50 keV x-rays, 200 MeV alpha, 250 keV alpha

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stochastic effects of radiation

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described by probability functions with no threshold and result in the same biological effect. cell killing, mutation induction and genetic effects are stochastic processes.

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free radicals involved in the indirect effect

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a free radical is an atom or molecule with an unpaired electron, i.e. has an odd number of electrons

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chronological sequence of events following cellular irradiation

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energy deposition, free radical repair, repair of sublethal damage, chromosome aberration formation

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describe the role of indirect effect in cellular radiobiology

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most indirect effect of radiation in cells is through water free radicals

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free radicals produced in cellular water

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water radicals are formed randomly through the cell, in the cytoplasm and the nucleus

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apoptosis

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also known as programmed cell death, is a cell death process that involves implosion of cells and the fragmentation of nuclear and genetic material.

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the principal chemical alteration induced in cells by ionizing radiation leading to cell death

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damage to nuclear DNA

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stages of mitotic growth for cells are divided into four phases

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G1, S(DNA synthesis), G2 and M (mitosis)

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which phase of the cell cycle is most radiosensitive

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the late G2 phase and mitotic cells are the most sensitive to radiation

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repair of sublethal damage occurs most efficiently

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in late responding normal tissues

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OER

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a measure of the radiosensitizing effect of oxygen in cells

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RBE

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a measure of the biological effectiveness of an experimental radiation relative to that of a standard photon source, like cobalt-60

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LET

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a measure of ionization density along charged particle tracks

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SER

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a measure of radiosensitizing effect for radiation modifiers other than oxygen

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cells are essentially fully radiosensitized at a pO2 of

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radiosensitivity of cells changes very little at O2 tensions above that found in venous blood (20-40 torr)

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cellular repair

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sublethal lesions are mostly fully repaired at dose rates of 0.01 Gy/min and lower.

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cellular repopulation

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repopulation requires cell doubling whose times are ~24hrs or longer

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alteration of free radical recombination

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ultrafast dose rates can lead to altered G values for free radicals

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RBE is dependent upon

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dose level, dose rate, LET, biological effect level

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cells are most radioresistance during which phase of the cell cycle

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most cells exhibit maximum radioresistance in late S-phase

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G1-phase

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the most variable phase in duration

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G2-phase

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the majority of radiation-induced division delay occurs in G2-phase

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M-phase

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the most radiosensitive phase of the cell cycle

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T90

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the best predictor of tumor response to hyperthermia

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hyperthermia for cancer treatment

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heat treatment should selectively kill the radioresistant hypoxic cells and promote reoxygenation

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nau will produce sea and vomiting

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doses above about 1 Gy

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depression of white cell count

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doses greater than 2-3 Gy will produce detectable changes in white cell count

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prolonged diarrhea

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doses above 6 Gy will produce severe diarrhea

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convulsions

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very high doses produce neurological symptoms and rapid death >50 Gy

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chromosomal aberrations in blood lymphocytes

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doses greater than about 0.1 Gy can produce detectable chromosome aberrations

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threshold dose for GI syndrome

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the lowest dose that can cause GI syndrome is ~6 Gy

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death at 21-28 days after whole body dose of 5 Gy would be due to

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hematopoietic damage

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radiation induced cataracts results from

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the accumulation of dead cells

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the most radiosensitive normal tissues

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bone marrow and ovary

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in the GI tract cell renewal takes place

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GI tract cell renewal takes place in the crypts

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the latent period for lung tissue injury

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2-7 months pnemonitis

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latent period for epidermis injury

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10-30 days

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latent period for intestinal mucosa injury

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4-7 days

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latent period for testis injury

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6-7 weeks

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latent period for peripheral lymphocytes injury

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within 2 days

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the average annual radiation exposure to the US population comes from

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indoor radon

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at what LET does one observe the maximum RBE for most biological effects

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100 keV/um

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measure of absorbed dose

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gray and rad

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genetically significant dose GSD

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represents the annual average gonadal dose corrected for relative child expectancy

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determine number of fatal cancers in a population

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population x exposure (Sv) x 0.04 fatal cancers/Sv

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dose from transatlantic flight

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0.5 mSv

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x-rays plus nuclear medicine contibute what dose to the US population

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0.39 mSv x-ray and 0.14 mSv Nuc Med. or 15% of total dose

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1 mSv

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100 mrem or 0.1 rem

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radon

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2.0 mSv

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natural sources other than radon

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1.0 mSv

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consumer products

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0.09 mSv

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medical exposures

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0.55 mSv

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nuclear fuel cycle

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0.0005 mSv

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dose producing CNS syndrome

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100 Gy

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typical D0 for hypoxic cells

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4 Gy

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dose to double the natural mutation rate

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1 Gy

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dose above which GI syndrome will be observed

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8 Gy

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which part of human anatomy is least sensitive to radiation

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body extremities