DNA crosslinking, sister-chromatid exchange and specific-locus mutations.
Chinese hamster ovary cells were treated with the DNA-crosslinking chemicals, mitomycin C (MMC) and porfiromycin (POR), and their monofunctional derivative decarbamoyl mitomycin C (DCMMC). After exposure, the cells were studied for the induction of sister-chromatid exchanges (SCEs) and mutations at the hypoxanthine phosphoribosyltransferase and adenine phosphoribosyltransferase loci. The frequency of SCEs varied significantly in successive sampling intervals, requiring the weighting of each interval by the percentage of second-division mitosis in that interval to obtain the mean SCE frequency for each dose. All 3 compounds were potent inducers of SCEs but weakly mutagenic. All 3 chemicals by concentration were approximately equally effective in inducing SCEs or mutations. When the induced SCEs and mutations were compared at equal levels of survival, DCMMC was slightly more effective than MMC or POR in inducing SCEs and somewhat less mutagenic. These results indicate that the DNA interstrand crosslink is not the major lesion responsible for the induction of SCE or mutation by these compounds.
D000228:Adenine Phosphoribosyltransferase / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002875:Chromosomes / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D003434:Crossing Over, Genetic; D004247:DNA / Q000235:genetics*; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008937:Mitomycins / Q000494:pharmacology; D009154:Mutation; D010053:Ovary; D012854:Sister Chromatid Exchange
D008937:Mitomycins; D004247:DNA; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase