Gene Mutation Assay Salmonella typhimurium

TABLE 25.1. Strains Commonly Used in the Salmonella/ Histidine Reversion (Ames) Assay for Detecting Mutations at the Histidine Locus 

Escherichia coli, employing reversion at the tryptophan locus. The WP2 strains used can only detect base-pair substitutions, given that the original trp mutation is a base-pair substitution. 

There are some obvious limitations to the use of prokaryotic assays for predicting responses in mammals, given the difference in cellular and genomic complexity between prokaryotes and eukaryotes. However, for hazard identification purposes, these prokaryotic assays are a useful component. 

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Catechol did not induce gene mutations in Salmonella typhimurium or DNA repair in a mouse host-mediated assay in Escherichia coli. 

Brusick and Matheson (1976) reported that 1,1-dimethylhydrazine failed to increase reversions in Salmonella typhimurium or Saccharomyces cerevisiae gene mutation assays with or without metabolic activation. A concentration-related response was observed in the mouse lymphoma assay (with activation). Dominant lethal tests were negative. 

Metabolic activation of 1,3-dichloropropene, as suggested by the use of specific inhibitors of metabolism in the Salmonella typhimurium gene mutation assay, proceeds via an hydrolytic-oxidative pathway the first step of which is hydrolysis to chloroallyl alcohol, which is then oxidized to chloroacrolein (Neudecker Henschler, 1986). 

Phosphine has been reported as negative for induction of reverse gene mutations up to cytotoxic doses in the Ames assay Salmonella typhimurium). Increased chromosomal aberrations were reported in Chinese hamster ovary (CHO) cells exposed to 2500 and 5000 ppm of phosphine without activation with the S9 fraction. Chromosomal aberrations in CHOs were also reported in cells tested with S9 activation at 2500 ppm, but not 5000 ppm. 

Salmonella typhimurium (stabilized TCE, preincubation assay) Gene mutation McGregor et al. 1989... 

The mutagenic potential of diisopropyl methylphosphonate was investigated using the Ames assay. The compound was obtained from two different sources and tested on Salmonella typhimurium strains TA-1535, TA-1537, TA-1538, TA-98, and TA-100, both with and without S-9 activation. The compound did not demonstrate mutagenic activity in any of the assays (Hart 1980). Diisopropyl methylphosphonate was also negative for gene mutation in Saccharomyces cerevisiae (Hart 1980). 

Prokaryotic organisms Salmonella typhimurium (Ames assay) Gene mutation — FMC 1992b Durad 550B... 

Salmonella typhimurium (reverse mutation) Escherichia coli (forward mutation, DNA modification) Saccharomyces cerevisia (reverse mutation) Bacillus subtilis (rec assay) Gene mutation or DNA modification Bruce and Heddle 1979 Dunkel et al. 1984 Fukunaga et al. 1982 Kharab and Singh 1985 Nestmann et al. 1979 Nishioka 1975 Rosenkranz and Poirier 1979 Simmon 1979b... 

Assays for Gene Mutations Salmonella Typhimurium reverse mutation assay (Ames test, / ... 

The bacterial and mammalian cell assays for gene mutation were developed to measure statistically significant increases in the numbers of mutant colonies derived from rare events many millions of exposed cells must be plated out to allow the assessment of mutation frequency. The Salmonella typhimurium reverse mutation assay ( Ames test) is carried out in a variety of different mutant strains selected to identify the various classes of mutation. The test generates many hundreds of Petri dishes for counting and is not practical for profiling. 

Kier LD, Brusick DJ, Auletta AE, et al. (1986) The Salmonella typhimurium/mammalian microsomal assay A report of the US Environmental Protection Agency Gene-Tox Program. Mutation Research 168 69-240. 

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