Lethal and potentially lethal lesions induced by radiation--a unified repair model

Abstract

A model of radiation action is described which unifies several of the major existing concepts which have been applied to cell killing. Called the lethal and potentially lethal (LPL) model, it combines the ideas of lesion interaction, irreparable lesions caused by single tracks, linear lesion fixation, lesion repair via first-order kinetics, and binary misrepair. Two different kinds of lesions are hypothesized: irreparable (lethal) and repairable (potentially lethal) lesions. They are tentatively being identified with DNA double-strand breaks of different severity. Two processes compete for depletion of the potentially lethal lesions: correct repair following first-order kinetics, and misrepair following second-order kinetics. Fixation of these lesions can also occur. The model applies presently only to plateau (stationary)-phase cells. Radiobiological phenomena described include effects of low dose rate, high LET, and repair kinetics as measured with repair inhibitors such as hypertonic solution and beta-arabinofuranosyladenine (beta-araA). One consequence of the model is that repair of sublethal damage and the slow component of the repair of potentially lethal damage are two manifestations of the same repair process. Hypertonic treatment fixes a completely new class of lesions which normally repair correctly. Another consequence of the model is that the initial slope of the survival curve depends on the amount of time available for repair after irradiation. The "dose-rate factor" occurring in several linear-quadratic formulations is shown to emerge when appropriate low-dose and long-repair-time approximations are made.