Mutagenic activity compounds

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). 

NishiokaH. 1975. Mutagenic activities of metal compounds in bacteria. MutRes 31 185-189. 

Simmon VF, Rosenkranz HS, Zeiger E. et al. 1979. Mutagenic activity of chemical carcinogens and related compounds in the intraperitoneal host- mediated assay. J Nat Cancer Inst 62 911-918. 

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. 

Simmon VF, Tardiff RG. 1978. The mutagenic activity of halogenated compounds found in chlorinated drinking water. In Water chlorination Environmental impact and health effects. Vol. 2. Ann Arbor, Ml Ann Arbor Science, 417-431. 

Shimizu N, Yasui Y, Matsumoto N. 1983. Structural specificity of aromatic compounds with special reference to mutagenic activity in Salmonella typhimurium - a series of chloro- or fluoro-nitrobenzene derivatives. Mutat Res 116 217-238. 

An extensive database has demonstrated that many chemicals that are positive in this test also exhibit mutagenic activity in other tests. There are, however, examples of mutagenic substances, which are not detected by this test reasons for these shortcomings can be ascribed to the specific nature of the endpoint detected, differences in metabolic activation, or differences in bioavailability. On the other hand, factors which enhance the sensitivity of the bacterial reverse mutation test can lead to an overestimation of mutagenic activity. The bacterial reverse mutation test may not be appropriate for the evaluation of certain classes of chemicals for example, highly bactericidal compounds (e.g., certain antibiotics) and those which are thought (or known) to interfere specifically with the mammalian cell replication system (e.g., some topoisomerase inhibitors and some nucleoside analogues). In such cases, mammalian mutation tests may be more appropriate. 

Figure 1. Oxidation and other reactions of dialiate and triallate indicating mutagenic activities of the products in the S. typhimurium TA 100 assay (revertants/ nanomole without activation/with activation / designates no data available). 2-Chloroacrolein is a dialiate metabolite in the mouse liver microsome-NADPH system. Dichloroallylsulfonic acid is a urinary metabolite of dialiate. The other compounds are potential metabolites of the respective thiocarbamates. The thio-carbamate sulfoxides are unstable at 25°C.

N,N-Dialkylthlo- and dithiocarbamate herbicides include several -alkyl and -benzyl compounds without mutagenic activity and three -chloroallyl derivatives which are promutagens,... 

Vogel, E., Blijleven, W.G.H., Kortselius, M.J.H. and Zijlstra, J.A. (1981) Mutagenic activity of 17 coded compounds in the sex-linked recessive lethal test in Drosophila melanogaster, in Progress in Mutation Research, Volume 1 Evaluation of Short-Term Tests Carcinogens (eds F.J. de Serres and J. Ashby), Elsevier, Amsterdam. 

The mutagenic activity of 2 -acetoxyNNN and 5 -acetoxyNNN was tested in S. typhimuriidm TA 100. Both compounds were mutagenic without activation, but with activity less than that of a-acetoxy NPy. The 5 -acetate showed maximum activity (840 His" " r vertants/ plate control=180) at a dose of 1.70 ymoles/plate. The 2 -acetate was weakly mutagenic (315 His" " revertants/plate for 1.28 ymoles/plate control=140). When NNN was tested at these doses in the presence of hepatic supernatants, no activity was observed. NNN was mutagenic at higher doses, however. These results are consistent with involvement of a-hydroxylation as an activation step for NNN. 

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