title: Methyl methanesulphonate (MMS) is clearly mutagenic in S. typhimurium strain TA1535; a comparison with strain TA100.
abstract: No mutagenicity or an uncertain mutagenic response has been reported in the literature for methyl methanesulphonate (MMS) in S. typhimurium strain TA1535 when using the plate assay. In our studies we found a reproducible mutagenic activity of 62 revertants/mumole and plate for MMS in strain TA1535 when using the preincubation assay. A dose-dependent increase in revertants was, however, observed only at fairly high doses (exceeding 4 mumole). Two different slopes were observed in the dose-response curve when testing MMS with strain TA100. Slope A is dependent on the error-prone response, possible only in strain TA100 due to the pKm101 plasmid (R factor) but not possible in strain TA1535 due to its umuDC deficiency. Slope B observed at higher doses (as in strain TA1535) could be explained through a GC----AT transition initiated by the O6-methylation of guanine. Our findings demonstrate that MMS induces back mutation in S. typhimurium strains carrying the hisG46 missense mutation due to the formation of O6-methylguanine. In the case of strain TA100 the pKm101 plasmid-mediated error-prone mechanism is, however, the predominant process in MMS mutagenesis which leads to a higher mutagenic response at much lower doses than the GT----AT transition in strain TA1535.
authors.affiliation: Institute of Toxicology, University of Würzburg, F.R.G.
authors.forename: E
authors.initials: E
authors.lastname: Eder
authors.forename: C
authors.initials: C
authors.lastname: Deininger
authors.forename: M
authors.initials: M
authors.lastname: Wiedenmann
mesh_terms: D004269:DNA, Bacterial / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens; D012486:Salmonella typhimurium / Q000235:genetics*; D013045:Species Specificity
chemical_list: D004269:DNA, Bacterial; D009153:Mutagens; D006147:Guanine; C008449:O-(6)-methylguanine; D008741:Methyl Methanesulfonate