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.

[1]  E. Zeiger,et al.  Salmonella mutagenicity tests: V. Results from the testing of 311 chemicals , 1992, Environmental and molecular mutagenesis.

[2]  H S Rosenkranz,et al.  Reproducibility of microbial mutagenicity assays: II. Testing of carcinogens and noncarcinogens in Salmonella typhimurium and Escherichia coli. , 1985, Environmental mutagenesis.

[3]  T. Cebula,et al.  Mutant alleles of tRNAThr genes suppress the hisG46 missense mutation in Salmonella typhimurium , 1994, Environmental and molecular mutagenesis.

[4]  M. Roberfroid,et al.  Mutagenicity of butadiene and butadiene monoxide. , 1978, Biochemical and biophysical research communications.

[5]  A. Araki,et al.  Improved method for mutagenicity testing of gaseous compounds by using a gas sampling bag. , 1994, Mutation research.

[6]  E. Zeiger,et al.  Salmonella mutagenicity tests: III. Results from the testing of 255 chemicals. , 1987, Environmental mutagenesis.

[7]  M. Roberfroid,et al.  The mutagenicity of butadiene towards Salmonella typhimurium. , 1980, Toxicology letters.

[8]  W. Piegorsch,et al.  The Ames test: the two-fold rule revisited. , 1996, Mutation research.

[9]  E. Zeiger,et al.  Salmonella mutagenicity tests: II. Results from the testing of 270 chemicals. , 1986, Environmental mutagenesis.

[10]  B. Ames,et al.  Detection of carcinogens as mutagens: bacterial tester strains with R factor plasmids. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Roger Woodgate,et al.  The SOS Response , 1998 .

[12]  C. Maragos,et al.  Mutagenicity of glyceryl trinitrate (nitroglycerin) in Salmonella typhimurium. , 1993, Mutation research.

[13]  J. Ashby,et al.  Weak and unexpected mutagenicity to Salmonella of the rat hepatocarcinogen methapyrilene. , 1988, Environmental and molecular mutagenesis.

[14]  T Ohta,et al.  Recommendations for the performance of bacterial mutation assays. , 1994, Mutation research.

[15]  T. P. Cameron,et al.  Genotoxicity of 6 oxime compounds in the salmonella/mammalian-microsome assay and mouse lymphoma TK +/- assay. , 1988, Mutation research.

[16]  B H Margolin,et al.  Strategies to reduce the cost of mutagenicity screening with the Salmonella assay. , 1985, Environmental mutagenesis.

[17]  B. Ames,et al.  Revised methods for the Salmonella mutagenicity test. , 1983, Mutation research.

[18]  E. Zeiger,et al.  Salmonella mutagenicity test results for 250 chemicals. , 1983, Environmental mutagenesis.

[19]  J. Theiss,et al.  Genotoxic classification of anticancer drugs. , 1985, Teratogenesis, carcinogenesis, and mutagenesis.

[20]  B. Ames,et al.  Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. , 1975, Mutation research.

[21]  V. Dunkel,et al.  Reevaluation of the mutagenicity and carcinogenicity of chemicals previously identified as “false positives” in the Salmonella typhimurium mutagenicity assay , 1989, Environmental and Molecular Mutagenesis.

[22]  E. Zeiger,et al.  Salmonella mutagenicity tests: IV. Results from the testing of 300 chemicals , 1988, Environmental and molecular mutagenesis.