Effect of radiomodifying agents on the ratios of X-ray-induced lesions in cellular DNA: use in lethal lesion determination.
The effect of three radiomodifying agents, cysteamine, hyperthermia, and hypoxia, on the induction of the major classes of X-ray-induced DNA lesions, was studied using mouse L cells and Chinese hamster V79 cells. The use of filter elution techniques allowed most of these studies to be conducted at X-ray doses within the survival-curve range. Cysteamine was found to protect against DNA single-strand breakage (ssb), DNA base damage, and DNA-protein crosslinkage. Hyperthermia had no effect on the level of DNA ssb or DNA base damage, but in L cells (but not in V79 cells) it increased the level of DNA-protein crosslinkage relative to DNA ssb. Hypoxia protected against DNA ssb, had no significant effect on the level of DNA base damage, and enhanced the level of DNA-protein crosslinkage relative to DNA ssb. These results support the previous suggestion that the X-ray-induced lethal lesion is DNA double-strand breakage. Implications of these findings for the mechanisms of formation of X-ray-induced DNA lesions are also discussed.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D003543:Cysteamine / Q000494:pharmacology*; D004247:DNA / Q000528:radiation effects*; D006358:Hot Temperature; D007739:L Cells / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D010100:Oxygen; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D011837:Radiation-Protective Agents; D003543:Cysteamine; D004247:DNA; D010100:Oxygen