Genetic analysis of mitomycin C-hypersensitive Chinese hamster cell mutants.
The genetic diversity of Chinese hamster cell mutants exhibiting hypersensitivity to the bifunctional alkylating agent mitomycin C has been examined. The eight mutants irs3, VH4, UV1, MC5, MMC1, MMC3, MMC4 and MMS2, are between 4- and 30-fold more sensitive to mitomycin C than their respective wildtype parental lines. A number of the mutants show phenotypic similarities to cultured cells from the human cancer-prone syndrome Fanconi's anaemia. Hybrids were formed between pairs of mutants using the thioguanine/ouabain resistant (TOR) hybridization and hypoxanthine/aminopterin/thymidine (HAT)/ouabain selection system and the mitomycin C response of pooled populations of hybrids assessed by constructing survival curves. In every case, hybrids formed between pairs of mutants exhibited a mitomycin C response indistinguishable from that of wildtype cells, indicating complementation. Therefore, the eight mutant lines examined represent eight distinct complementation groups for mitomycin C-hypersensitivity. The results are in contrast to the complementation analysis of UV-sensitive Chinese hamster cell mutants and indicate that the response of mammalian cells to mitomycin C-induced DNA damage is complex and involves a large number of genes.
School of Biological Sciences, University of Wales, Swansea, UK.
N J
NJ
Jones
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004249:DNA Damage / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005199:Fanconi Anemia / Q000235:genetics; D005816:Genetic Complementation Test; D014644:Genetic Variation; D006801:Humans; D006824:Hybridization, Genetic; D016685:Mitomycin / Q000494:pharmacology*; D009154:Mutation; D010641:Phenotype
D016685:Mitomycin