Deoxycytidine kinase-deficient mutants of Chinese hamster ovary cells are hypersensitive to DNA alkylating agents.
Chinese hamster ovary cell strains deficient in deoxycytidine kinase activity were selected by isolating mutants resistant to high concentrations of the analogue arabinosyl cytosine. Mutants isolated were deficient in the pool of dCTP, supporting earlier a suggestion that the deoxycytidine kinase may play a role in the turnover and maintenance of the dCTP pool. Consistent with earlier observations that increased intracellular levels of dTTP relative to dCTP lead to increased sensitivity to monofunctional DNA alkylating agents, deoxycytidine kinase-deficient mutants showed a 2-5-fold increase in sensitivity to the cytotoxic and mutagenic effects of one agent, ethyl methanesulfonate (EMS). The survival of the two kinase-deficient strains after mutagen treatment was clearly related to dCTP level as the strain with lowest dCTP was most sensitive to EMS. Thus hypersensitivity to this class of DNA damaging agents can result from cellular mutations decreasing the intracellular level of dCTP.
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D006224:Cricetinae; D003412:Cricetulus; D003570:Cytidine Triphosphate / Q000032:analysis; D004247:DNA / Q000378:metabolism*; D003842:Deoxycytidine Kinase / Q000172:deficiency*; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D005260:Female; D009154:Mutation; D010053:Ovary / Q000187:drug effects* / Q000201:enzymology; D010770:Phosphotransferases / Q000172:deficiency*; D013942:Thymine Nucleotides / Q000032:analysis
D000477:Alkylating Agents; D013942:Thymine Nucleotides; D003570:Cytidine Triphosphate; D004247:DNA; D005020:Ethyl Methanesulfonate; D010770:Phosphotransferases; D003842:Deoxycytidine Kinase; C024157:thymidine 5'-triphosphate