Bacterial strains, mutagenicity

The Ames test involves the reversion from a his— to his+ phenotype in any one of multiple bacterial strains (usually five strains are tested simultaneously). If the addition of test compound to a his— strain of bacteria allows them to grow on histidine deficient media, the obvious conclusion is compound-induced mutagenesis and a high potential hazard for the compound being carcinogenic. This test can also be conducted in the presence or absence of metabolic activation, in order to provide more information on potential risks (i.e., the parent compound may not be mutagenic, but the primary metabolite may present a safety risk). In practice, a positive Ames test almost always leads to discontinuing work on a compound of interest, and so these data are always collected prior to nomination of a compound for development. 

Methyl acetate was not mutagenic in a number of bacterial strains with or without metabolic activation." ... 

PNA was mutagenic in vitro in some bacterial strains and in chromosomal aberration studies. ... 

Ecoflex (powder) was tested for its mutagenic potential on the basis of its ability to induce point mutations in several bacterial strains Salmonella typhimurium and Escherichia coll) in a reverse mutation assay (Ames test), according to OECD guideline 471. Results revealed that the polyester is not mutagenic to bacteria. 

Crebelli, R., S. Fuselli, G. Conti, L. Conti, and A. Carere, Mutagenicity Spectra in Bacterial Strains of Airborne and Engine Exhaust Particulate Extracts, Mutat. Res., 261, 237-248 (1991). 

Bis(bromomethyl)propane-l,3-diol was mutagenic in only one of several bacterial strains tested, and only with metabolic activation. In cultured mammalian cells, it was only weakly active in tests for chromosomal aberrations and sister chromatid exchanges. Micronucleus formation, indicative of chromosomal damage, was induced in cells from mice exposed to 2,2-bis(bromomethyl)propane-l,3-diol in vivo. 

Trichloroethane did not cause mutation in plants or sex-linked mutation in Drosophila. It did not induce DNA damage, gene conversion, mutation or aneuploidy in yeast or genetic crossing-over or aneuploidy in fungi, but it was mutagenic to some bacterial strains. 

Figure 8. Mutagenic activity of a fractionated LH20 drinking water concentrate (neutral fraction) as detected with nitroreductase-deficient bacterial strains. LH20 fractionated drinking water concentrates were tested in the Salmonella mutagenicity test as described in Materials and Methods. Each point represents the average value of three plates.

The Ames Salmonella typhimurium assay [3, 21-26] is the most widely used test to evaluate the mutagenic activity of xenobiotic compounds. The assay serves as a quick and relatively inexpensive test to estimate the carcinogenic potential of a compound. It makes use of a variety of bacterial strains to screen compounds for... 

A QSAR model was developed to test the mutagenicity of 117 nitro-aromatic compounds in bacterial strain cells without metabolic activation [74]. It was shown that hydrophobicity plays a crucial role in determining the relative mutagenicity of most of the compounds studied. The mutagenicity of the nitro-aromatic compounds increases slowly at low logR and then decreases rapidly at high log P. It was suggested that a combination of adverse hydrophobic and steric effects could explain these observations. In a subsequent analysis, Debnath and Hansch [75]... 

TABLE 5-2 Bacterial Strains Used in Mutagenicity and Genotoxicity Assays... 

Chlorobenzene was not mutagenic in several bacterial strains of Salmonella typhimurium or Escherichia coli and was negative in rat hepatic DNA repair assays however, it was weakly positive in a mouse micronucleus assay. Chlorobenzene induced transformation in Fischer 344 adult rat liver cell lines, but was not genotoxic to hepatocytes. In addition, it did not induce DNA repair in the rat he-patocyte primary culture DNA repair assay. 

Mutagenesis results are dependent on the bacterial strain and copper compound evaluated. Mammalian cell tests indicate a positive mutagenic response. 

A), 3-[4-(methylthio)-3-butenyl]-5-isobutyl-2-thiohydantoin, (B), 3-[4-(methylthio)-3-butenyl]-5-benzyl-2-thiohydantoin and (C), 3-[4-(methylthio)-3-butenyl]-5-[2-(methyl-thio)ethyl]-2-thiohydantoin. Symbols , Salmonella typhimuriumTA98 was simultaneously incubated with IQ (0.5 pg) and the 3,5-disubstituted 2-thiohydantoins (0-500 pg/ml) for 20 min at 37° C and then cultured for 48 h at the same temperature , the bacterial strain was treated with the same amount of IQ for 20 min at 37° C, rinsed with a buffered saline to eliminate the mutagen, and incubated with the test compounds for an additional 20 min. The bacteria were cultured for 48 h at 37° C. Mutagenicity is expressed in terms of the percentage in the revertant number found with or without the test compounds, where the mutagenicity of IQ is defined as 100%. 

The Ames test is extranely simple and fast. A strain of bacteria is cultured that is unable to grow on a minimal medium devoid of histidine. When mixed with the suspected mutagen, some of the bacteria may mutate into a bacterial strain capable of growth on the minimal growth medium. Presence of bacterial colonies growing on plates containing the minimal medium indicates that the substance is, indeed, capable of mutagenicity. 

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