Salmonella typhimurium, mutagens

The results of the Salmonella/Typhimurium Mutagenicity (Ames) assay for the feed and liquid products are given in Table III. 

In addition to the rodent bioassay, the aromatic amines have been studied in the shorter term test Salmonella typhimurium mutagenicity as well as in a variety of acute toxicity assays. A number of QSARs have been generated from such data. The work of Hansch in recent years has demonstrated that the comparison of the QSAR models obtained in different systems, by putting them in a wider perspective, can provide useful clues in the study of the mechanisms of action of individual chemical classes, and can give precious hints on how appropriate the specific models and parameters selected are (Hansch, 2001 Hansch et al., 2002). An exercise of the mechanistic comparison of QSARs has been performed on aromatic amines (Benigni and Passerini, 2002). The results are detailed below. 

Azathioprine gave positive results in the Ames Salmonella typhimurium mutagenicity assay, both with and without metabolic activation, in the TAIOO strain. Negative results were found for the TA98 strain under similar test conditions. Azathioprine has been shown to induce chromosomal aberrations in human and rabbit lymphocytes in vitro, however, it did not induce sister chromatid exchanges in either... 

Previous studies have shown that most of the direct-acting Salmonella typhimurium mutagenic activity (>50%) in diesel particulate extracts is concentrated in chemical fractions which contain compounds of moderate polarity (1-4). These moderately-polar fractions have been found to consist... 

Physicochemical properties requked include melting/boiling point, vapor pressure, solubiUty, and flammabiUty/explosion characteristics. The toxicological studies include acute toxicity tests, oral, inhalation, and dermal skin and eye kritation skin sensiti2ation subacute toxicity, oral, inhalation, and dermal and mutagenicity tests. In vitro reverse mutation assay (Ames test) on Salmonella typhimurium and/or E.scherichia coli and mammalian cytogenic test. In vivo mouse micronucleus test. 

Acute oral toxicity (rat)3 Ames mutagenicity screening test (Salmonella typhimurium)... 

Three examples concerning toxicity of heterogeneous data sets are given below. The first [50] relates to mutagenicity to Salmonella typhimurium of aromatic and heteroaromatic nitro-compounds ... 

The mutagenic activity of the extracts was assayed using Salmonella typhimurium strain TA 1535, as described by McCann et al. (58). Ten ul of fish extract were spot-tested without addition of an S9-enzyme preparation (57). MNNG (20 ug/plate) was used as a positive control. 

Sayama M, M Inoue, M-A Mori, Y Maruyama, H Kozuka (1992) Bacterial metabolism of 2,6-dinitrotoluene with Salmonella typhimurium and mutagenicity of the metabolites of 2,6- dinitrotoluene and related compounds. Xenobiotica 22 633-640. 

Some toxicity studies were performed analyzing Bfx and Fx mutagenic effects [240-242], For example, Bfx and Bfz nitro-substituted were tested for mutagenicity in Salmonella typhimurium (S. typhimurium) TA 98 and TA 100 strains with and without metabolic activation (Ames test). All the Bfx (10/10) and some of the Bfz (9/15) are mutagenic without activation. Other study has demonstrated benzofuroxan (128, Fig. 20) is mutagenic in the Luria and Del-brueck s fluctuation test, with Klebsiella pneumoniae, and in the Ames test. In another study it has been found that compound 137 (Fig. 21) is not mutagenic to S. typhimurium. 

Table 1 Antimutagenic Effects of Flavones on Mutagenicity Induced by IQ IN Salmonella typhimurium TA98...

MacGregor, J. T. Jurd, L. Mutagenicity of plant flavonoids structural requirements for mutagenic activity in Salmonella typhimurium. Mutat. Res. 1978, 54, 297-309. 

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). 

Genotoxic Effects. The Ames test with Salmonella typhimurium with and without s9 liver fractions from male Syrian golden hamsters or Sprague-Dawley rats indicates that hydrogen sulfide is not a mutagen (EPA 1984). A summary of genotoxicity studies is presented in Table 2-3. 

Berglin EH, Carlsson J. 1986. Effect of hydrogen sulfide on the mutagenicity of hydrogen peroxide in Salmonella typhimurium strain TA102. Mutat Res 175 5-9. 

Connor TH, Forti GC, Sitra P, et al. 1979. Bile as a source of mutagenic metabolites produced in vivo and detected by Salmonella typhimurium. Environ Mutagen 1 269-276. 

Khudoley W, Mizgireuv I, Pliss GB. 1987. The study of mutagenic activity of carcinogens and other chemical agents with Salmonella typhimurium assays Testing of 126 compounds. Arch Geschwulstforsch 57 453-462. 

Lijinsky W, Andrews AW. 1980. Mutagenicity of vinyl compounds in Salmonella typhimurium. Teratogenesis Carcinog Mutagen 1 259-267. 

Mutagenicity. The mutagenicity of nitro PAHs has been studied most extensively in the Ames Salmonella typhimurium reversion assay ( 5). The mutagenicities of representative nitro PAHs in this assay are shown in Table I. Some of the more important features regarding their mutagenicity can be summarized as follows ... 

Table I. Mutagenicity of Representative Nitro PAHs in Salmonella typhimurium strains TA98 and TA100 (revertants per nmole)...

Salmonella typhimurium. Although most nitro PAHs are direct-acting mutagens in Salmonella typhimurium, these compounds must be metabolized to bind covalently to DNA (71,92,112). S. typhimurium contains a family of nitroreductases which are capable of reducing nitro PAHs, and strains which are deficient in these enzymes generally show decreased sensitivity toward nitro PAH-induced mutations (27,92,113-114). These observations suggest that reduced metabolic intermediates may be the critical reactive electrophiles. 

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