Salmonella typhimurium absence

In the bacterial mutation test, the mutagenic potential of a pharmaceutical and its metabolites is evaluated by measuring and quantifying its ability to induce reverse mutations at selected loci of Salmonella typhimurium or Escherichia coli in the presence and absence of metabolic activation. This test system has been shown to detect a diverse group of chemical mutagens.3,4 The technical details of this test have been reported in the literature.5-7... 

The test is commonly employed as an initial screen for genotoxic activity and, in particular, for point mutation-inducing activity. It detects point mutations, which involve substimtion, addition or deletion of one or a few DNA base pairs. The reverse mutation test in either Salmonella typhimurium or Escherichia coli detects mutation in an amino acid requiring strain (histidine or tryptophan, respectively) to produce a strain independent of an outside supply of amino acid. The principle of the test is that it detects mutations, which revert mutations present in the test strains and restore the functional capability of the bacteria to synthesize an essential amino acid. The revertant bacteria are detected by their ability to grow in the absence of the amino acid required by the parent test strain. 

Acetamide was mutagenic in Escherichia coli and Salmonella typhimurium-, this effect was independent of dose. Acetamide produced morphological transformation in Syrian hamster embryo cells in the absence of metabolic activation. However, acetamide did not induce reversions in several Salmonella typhimurium strains. ... 

Diethanolamine was not mutagenic to Salmonella typhimurium strains TAIOO, TA1535, TA1537, TA1538 or TA98 in three studies, or to Escherichia coli WP2 uvrA in a single study, in the presence or absence of exogenous metabolic activation. It did... 

A-Nitrosodiethanolamine was mutagenic to Salmonella typhimurium in most assays in the presence of exogenous metabolic activation systems and in some assays in the absence of such systems. 

Dioxane with or w ithout metabolic activation did not induce differential DNA repair in Escherichia coli K-12 uvrB/rec A and was not mutagenic in Salmonella typhimurium or in L5178Y mouse lymphoma cells. In Chinese hamster ovary CHO cells, it did not cause chromosomal aberrations, although it did cause a slight increase in sister chromatid exchange in the absence of metabolic activation. It has also been reported to cause morphological transformation of BALB/c 3T3 mouse cells. 

Resorcinol did not induce gene mutations in Salmonella typhimurium or in Escherichia coli strains in either the presence or absence of an exogenous metabolic activation system. 

No increases were observed in the frequency of micronucleated erythrocytes from the peripheral blood of mice exposed by inhalation for 13 weeks. This appears to be the only study with tetrafluoroethylene itself. However, 5 -(l,l,2,2-tetrafluoroethyl)-L-cysteine was not mutagenic to Salmonella typhimurium in either the presence or absence of an exogenous metabolic system based upon rat kidney S9. 

Chlorodifluoromethane is mutagenic to Salmonella typhimurium but it did not induce either mutation or gene conversion in Saccharomyces cerevisiae. Chlorodifluoromethane did not induce mutations at the hprt locus or imscheduled DNA synthesis in mammalian cell lines in the presence or absence of an exogenous metabolic activation system. In vivo, it did not induce chromosomal aberrations in bone-marrow cells or dominant lethal effects (lARC, 1987b). These conclusions are supported by a more recent review (WHO, 1991). 

Diethy Ihydrazine is weakly mutagenic to Salmonella typhimurium TAIOO and particularly TAI 02. but only in the absence of an exogenous metabolic activation system. The activity in strain TA 102 rapidly disappears with time of incubation, so that after 7 h it is halved and after 11 h, there is no activity. 

Ames Test The Ames test, developed by Bruce Ames and his coworkers at the University of California, Berkeley, depends on the ability of mutagenic chemicals to bring about reverse mutations in Salmonella typhimurium strains that have defects in the histidine biosynthesis pathway. These strains will not grow in the absence of histidine but can be caused to mutate back to the wild type, which can synthesize histidine and hence can grow in its absence. The postmitochondrial supernatant (S-9 fraction), obtained from homogenates of livers of rats previously treated with PCBs in order to induce certain cytochrome P450 isoforms, is also included in order to provide the activating enzymes involved in the production of the potent electrophiles often involved in the toxicity of chemicals to animals. 

As indicated in Table 2-4, 2-nitrophenol did not increase the frequency of reverse mutations in Salmonella typhimurium or in Escherichia coli in the presence or absence of metabolic activation, nor did it induce DNA damage when tested in Bacillus subtilis. No data were available regarding genotoxic properties of 2-nitrophenol in eukaryotic organisms. 

Salmonella typhimurium/Escherichia coli Plate Incorporation Mutation Assay in the Presence and Absence of Induced Rat... 

Salmonella typhimurium/ Escherichia coli Plate Incorporation Mutation Assay in the Presence and Absence of Induced Rat Liver S-9 ICH S2A Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals, ICH S2B Genotoxicity A Standard Battery of Genotoxicity Testing of Pharmaceuticals 2-A 4-6 10,000-15,000... 

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