Effect of misonidazole on formation of thymine base damage by gamma rays in HeLa cells

The effect of the radiosensitizer misonidazole on the formation of thymine base damage of the 5,6-dihydroxydihydro-thymine-type by gamma rays was measured under aerobic and hypoxic conditions. HeLa cells, prelabled with [3H-methyl]-thymidine, were suspended in phosphate buffered saline in the presence and absence of misonidazole. Concentrations up to 20 mM were used. The cell suspensions were irradiated at 12-140 with 60Co gamma rays. Dose response curves under aerobic and hypoxic conditions showed a much-depressed base damage formation under hypoxia, which was created by blowing a stream of nitrogen across the cell suspensions for 30 minutes on ice. The presence of higher concentrations of misonidazole decreased the formation of thymine based damage under aerobic conditions but had little or no detectable effect under hypoxia. It is concluded that an effect on the level of formation of thymine base damage is not primarily responsible for the radiosensitization of misonidazole under hypoxic conditions. 12 references, 3 figures