The effect of nitroimidazole and nitroxyl radiosensitizers on the post-irradiation synthesis of DNA.
The modification of DNA damage by three radiosensitizing drugs, present during gamma-irradiation of hypoxic Chinese hamster cells, was investigated. Both 2-methyl-5-nitroimidazole-1-ethanol (metronidazole) and 1-(2-nitro-1-imidazole)-3-methoxy-2-propranol (Ro-07-0582) were found to cause large increases in the yield of DNA single-strand breaks (SSB); triacetoneamine-N-oxyl (TAN) was found to have only a small effect on SSB production. The three drugs tested did not inhibit the rejoining of SSB. 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. TAN pre- and post-treatments were found to have no significant effect on subsequent DNA synthesis.
D002478:Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D009593:Nitroimidazoles / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014216:Triacetoneamine-N-Oxyl / Q000494:pharmacology*
D003037:Cobalt Radioisotopes; D003497:Cyclic N-Oxides; D004277:DNA, Single-Stranded; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D014216:Triacetoneamine-N-Oxyl