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Effects of three radiosensitizing drugs on radiation-induced DNA damage in hypoxic mammalian cells Hohman, William Frank


The modification of DNA damage by 3 radiosensitizing drugs, present during γ-irradiation of hypoxic Chinese hamster cells, was investigated. The method of alkaline sucrose gradients (ASG's) was used to determine the size distribution of DNA molecules. Both metronidazole and Ro-07-0582 were found to cause large increases in the yield of DNA single strand breaks (SSB's); triacetoneamine-N-oxyl (TAN) was found to have only a small effect on SSB production. A pulse label and chase procedure was used to examine post-irradiation DNA synthesis. TAN present during irradiation under hypoxia was found to cause interruptions in subsequent DNA synthesis. Metronidazole and Ro-07-0582 had no effect on post-irradiation DNA synthesis. In addition, the effects of pre- and post-irradiation exposure to TAN were investigated, since these treatments have shown increased cell killing in survival studies (Agnew and Skarsgard, 1972). TAN pre- and post-treatments were found to have no significant effect on subsequent DNA synthesis.

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