Chemicals mutagenic in Salmonella typhimurium strain TA1535 but not in TA100.
The standard Salmonella mutagenicity test uses two strains of Salmonella typhimurium (TA1535 and TA100) containing the same base pair substitution mutation (hisG46). These strains differ only in that strain TA100 contains the plasmid pKM101, whose mucAB gene products enhance SOS mutagenesis. This makes strain TA100, in general, the more sensitive of the two for mutagen detection, raising the question as to whether or not to include strain TA1535 in the core battery of strains in routine testing. Out of 659 chemicals judged as mutagens in the S. typhimurium assay when subjected to the National Toxicology Program's screening protocol, 36 (5%) were evaluated as positive in strain TA1535 but not in strain TA100. Of these, 23 were judged as negative and 13 as equivocal in strain TA100, and 5 were positive or equivocal in at least one other strain (TA97 or TA98). In general, the data on these chemicals indicate that the absolute increases in revertants per plate induced in strain TA1535 were too small to have been judged as positive if similar increases occurred in strain TA100, which has a much higher spontaneous background. For three chemicals (acetaldehyde oxime, 6-mercaptopurine, and 1,3-butadiene) the absolute increases in revertants in strain TA1535 greatly exceeded those in strain TA100. Evaluation of the reproducibility of these findings and of the mechanisms and relevance of unique TA1535 positives should be useful when decisions are made as to whether this strain should be kept as a part of the core battery of strains in the S. typhimurium assay.
Prival
M J
MJ
Genetic Toxicology Branch (HFS-236), Food and Drug Administration, Washington, DC 20204, USA. mprival@bangate.fda.gov
Zeiger
E
E
D004305:Dose-Response Relationship, Drug; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D017354:Point Mutation / Q000187:drug effects*; D015203:Reproducibility of Results; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D013045:Species Specificity
D009153:Mutagens