The Overall Radiobiological Effect: The Evolution of Radiation Damage

Abstract

1. The evolution of radiation damage is given in terms of sequential events each with a different time scale, 2. Damage is initiated by ionizations or excitations occurring either directly in the biological target or in the surrounding water which may dissociate into chemically reactive free radicals, principally e aq − , H° and OH°. 3. DNA is most probably theprincipal biological target and double strand breaks (DSB) are likely to develop into a lethal event. 4. The biological lesion may be either potentially lethal (PL). The latter may be either repaired or transformed into a lethal lesion through its fixation or misrepair. 5. The biological lesion is expressed on the cellular level as either cell killing or transformation. The frequency of both cellular effects can be expressed as a sum of a linear and a quadratic function of the dose (F = aD + sD2). 6. Cell killing results in nonstochastic early and late tissue effects or reactions. Both the severity (grade) and frequency (incidence) are dose-dependent. A threshold dose is required which corresponds to the minimum dose needed to reduce the number of functioning cells to a certain critical level required for the expression of a given reaction. Subsequently the dose-incidence relationship is S-shaped. Tissues with a rapid turnover rate express early reactions while late reactions characterize tissues with slow cell renewal. 7. Transformations are expressed as mutations and carcinogenesis. Both are all or nothing effects with no threshold dose since any cellular transformation is associated with a certain probability of being expressed (stochastic effects). The probability of occurrence (but not the severity) is dose-dependent. 8. Nonstochastic processes are relevant to clinical radiotherapy. The radiocurability of a tumour depends on the possibility of obtaining a high probability of tumour control at an acceptable level of normal tissue damage. 9. Stochastic effects are relevant to low dose exposure (radiation protection) where the linear term of the dose-effect relationship predominates and where the probability of the mutagenic and carcinogenic effects are cumulative and not dependent on the dose rate.