GENETIC-ANALYSIS OF MITOMYCIN C-HYPERSENSITIVE CHINESE-HAMSTER CELL MUTANTS

The genetic diversity of Chinese hamster cell mutants exhibiting hyper sensitivity 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 th eir respective wildtype parental lines. A number of the mutants show p henotypic similarities to cultured cells from the human cancer-prone s yndrome Fanconi's anaemia. Hybrids were formed between pairs of mutant s using the thioguanine/ouabain resistant (TOR) hybridization and hypo xanthine/aminopterin/thymidine (HAT)/ouabain selection system and the mitomycin C response of pooled populations of hybrids assessed by cons tructing survival curves. In every case, hybrids formed between pairs of mutants exhibited a mitomycin C response indistinguishable from tha t 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 c omplementation analysis of UV-sensitive Chinese hamster cell mutants a nd indicate that the response of mammalian cells to mitomycin C-induce d DNA damage is complex and involves a large number of genes.