The dose-response relationship for ethyl methanesulfonate-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster ovary cells.
The frequency of ethyl methanesulfonate (EMS)-induced mutations to 6-thioguanine resistance in a Chinese hamster ovary cells clone K1-BH4 was studied at many EMS doses including the minimally lethal range (0-100 microng/ml) as well as the exponential killing portion (100-800 microng/ml) of the survival curve. The mutation frequency increases approximately in proportion with increasing EMS concentration at a fixed treatment time. The pooled data for the observed mutation frequency, f(X), as a function of EMS dose X, is adequately described by a linear function f(X)=10(-6)(8.73+3.45 X), where 0 less than or equal to X less than or equal to 800 microng/ml. One interpretation of the linear dose-response is that, as a result of EMS treatment, ethylation of cellular constituents occurs, which is directly responsible for the mutation. Biochemical analyses demonstrate that most of the randomly isolated 6-thioguanine-resistant variants possess a highly reduced or undetectable level of HGPRT activity suggesting that the EMS-induced mutations to 6-thioguanine resistance affect primarily, if not exclusively, the HGPRT locus.
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured / Q000187:drug effects*; D002874:Chromosome Mapping; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005020:Ethyl Methanesulfonate / Q000008:administration & dosage; D014644:Genetic Variation; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D066298:In Vitro Techniques; D008698:Mesylates; D009154:Mutation; D011336:Probability; D013866:Thioguanine / Q000494:pharmacology
D008698:Mesylates; D005020:Ethyl Methanesulfonate; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine