Radiosensitization of Hypoxic Mammalian Cells by Diamide: II. Studies of Mechanism

Abstract

Diamide [diazenedicarboxylic acid bis(N,N''-dimethylamide)] radiosensitizes hypoxic Chinese hamster [ovary] cells by decreasing the shoulder of the survival curve (at low concentrations) and increasing the slope (at high concentrations). The mechanisms responsible for these 2 phenomena were studied by irradiating cells under different conditions of temperature and substrate availability and measuring either their survival or DNA damage (chromosome aberrations and strand breaks). Different mechanisms were responsible for the 2 effects. The effect on the shoulder appeared to be due to oxidation of endogenous nonprotein sulfhydryls and reduced pyridine nucleotides, compounds that normally effect rapid chemical repair of certain (single-hit type?) lesions. The slope effect may be due to reactions with DNA similar to those that were described for the electron-affinic compounds. These results, together with the finding that hypoxic cells remained sensitized after the removal of diamide when they were irradiated in the cold, provide a useful model and a new experimental approach to the question of chemical radiosensitization.