Recovery from Sub-lethal X-ray Damage of Mammalian Cells during Inhibition of Synthesis of Deoxyribonucleic Acid

Abstract

THE ability of mammalian cells to recover from sub-lethal X-ray damage was first demonstrated by Elkind et al.¹, who found that the effect of two doses separated by an interval of time was less than the effect of the same total dose given as a single exposure. This recovery phenomenon has been confirmed in vitro and in vivo in a wide variety of mammalian cell types^2–5. These investigations characterized the dependence of radiation sensitivity on the interval between divided doses as having an initial increase to a maximum followed by a minimum and a subsequent new maximum plateau. The nature of the recovery curve between the fractionated doses suggested that the curve may be the result of two opposing reactions and that one reaction at least may be dependent on the metabolic state of the cell. Hence, the recovery curve may be subject to alteration when a major metabolic process is inhibited. We recently reported that the repair processes were operative under conditions in which DNA thymine was partially replaced by 5-bromouracil⁵. Reported here are the results of experiments designed to test whether the recovery phenomenon requires uninterrupted DNA synthesis during the interval between fractionated doses. In these experiments 5-fluoro-deoxyuridine (FUDR) was used as an inhibitor of DNA synthesis.