Different genetic alterations underlie dual hypersensitivity of CHO mutant UV-1 to DNA methylating and cross-linking agents.
CHO mutant UV-1, isolated on the basis of hypersensitivity to UV radiation (254 nm), was further characterized with respect to sensitivity to classes of DNA damaging agents in a differential cytotoxicity (DC) assay. Compared to its parental strain, Gly- A, UV-1 was dramatically (10- to 100-fold) hypersensitive to both DNA methylating and cross-linking agents. In addition, UV-1 was moderately (two- to fourfold) hypersensitive to several other classes of mutagens. DNA isolated from UV-1 or Gly- A after exposure to 14C-labeled methylnitrosourea (MNU) contained similar amounts of label, thus ruling out differences in uptake or binding. Three phenotypic revertants of UV-1 were resistant to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and other methylating agents but retained hypersensitivity to cross-linking agents. Moreover, fusion of UV-1 with two different UV-sensitive CHO mutants also having hypersensitivity to cross-link and methylation damage produced hybrids resistant to mitomycin C (MMC) but not to methyl methane sulfonate (MMS). Since the methylation and cross-link sensitivities were uncoupled in both genetic tests, the complex phenotype of UV-1 is likely due to more than one genetic alteration.
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D005816:Genetic Complementation Test; D007364:Intercalating Agents / Q000494:pharmacology*; D008745:Methylation; D009154:Mutation; D010053:Ovary; D013329:Structure-Activity Relationship
D000477:Alkylating Agents; D003432:Cross-Linking Reagents; D007364:Intercalating Agents; D004247:DNA