Interactions of Radioprotectors and Oxygen in Cultured Mammalian Cells: I. Dithiothreitol Effects on Radiation-Induced Cell Killing

Abstract

Radioprotection in vitro by sulfhydryl (SH)-containing compounds is usually greater in aerated than in hypoxic cells. This observation has been cited recently as one of the reasons for the relatively greater effectiveness of radioprotectors such as WR-2721 in normal tissues compared to tumor cells. It is demonstrated herein, however, that hypoxic V79 cells irradiated in vitro under carefully controlled conditions are protected to a greater extent by low concentrations (1-2 mM) of the SH compound dithiothreitol (DTT) than are aerated cells. The reverse, more general phenomenon is seen at high concentrations of DTT (greater than 2 mM). This complex SH concentration and oxygenation dependence results in an increase in the oxygen enhancement ratio (OER) at low concentrations of DTT relative to the OER in the absence of DDT, followed by a decrease in OER at concentrations greater than 2 mM DTT. The possible radiation chemical basis for this finding and its importance to the clinical use of SH-containing radioprotectors are discussed.