Isolation of alkylating agent-sensitive Chinese hamster ovary cell lines

Abstract

Six derivatives of a Chinese hamster ovary cell line have been isolated by selection for hypersensitivity to the cytotoxic effects of the monofunctional alkylating agent methyl methane sulphonate (MMS). These cells are up to 6-fold more sensitive to MMS than the parental line, as estimated from D37 values, and are cross-sensitive to methyl nitrosourea, as well as to the ethyl derivatives of these drugs. Comparisons of their sensitivities to the bifunctional alkylating agents cis-platinum (II) diammine dichloride, mitomycin C and melphalan reveals marked phenotypic diversity, with only one mutant, designated MMS-2, exhibiting appreciable hypersensitivity to all of these agents. No striking hypersensitivity to raditation or to the purine analogue caffeine is apparent in any of the mutant lines. Based on their profiles of sensitivity to DNA damaging agents, it would appear that these mutants are phenotypically unlike any previously described mammalian cell mutants and probably represent a number of different genetic complementation groups. These mutants may facilitate an investigation into the mechanisms of repair of alkylation damage in mammalian cells and could prove to be suitable host for the cloning of human DNA repair genes.