Mutagenicity in Salmonella typhimurium TA98 and TA100 of nitroso and respective hydroxylamine compounds

Five aromatic nitroso compounds were prepared and their mutagenicity in Sal monella typhimurium strains TA98 and TA100 compared with that of the corres ponding hydroxylamines and the previously studied nitroarenes. A remarkable correspondence of the dose-response curves was observed between the nitros o and the respective hydroxylamine compounds. This effect could be observed in TA98 and TA100. It was only marginally dependent on the metabolical act ivation by rat liver S9-mix. Even the presence of a bulky alkyl substituent either near to the functional group, or far away from it, previously shown to considerably influence the mutagenic properties of nitroarenes, does no t remarkably affect the properties of the nitroso and hydroxylamine species . The similarity between the latter two is likely to be due to a fast reduc tion of the nitrosoarenes to the hydroxylamine species under the test condi tions. It seems that enzymes are not responsible for that reduction step, b ecause sterical crowding near the functional group does not influence that behaviour. The test results of the aromatic hydroxylamines bearing a bulky substituent show that there are at least two ways to influence the mutagenicity of an aromatic nitro compound by such a group. A substituent near the functional group (ortho-position) disturbs the enzymatic reduction of the nitro group, because 3-tert-butyl-4-hydroxylaminobiphenyl and its corresponding nitroso compound are highly mutagenic, whereas 3-tert-butyl-4-nitrobiphenyl was pr eviously shown to be inactive even after addition of S9-mix. In contrast, 4 '-tert-butyl-4-hydroxylaminobiphenyl with the tert-butyl group "far away" f rom the hydroxylamino functionality clearly shows decreased mutagenic activ ity suggesting a different influence of a substituent in that position. In addition, the substance shows only little cell toxicity even at higher conc entrations. Both effects could be due to a reduced effective dose of the hy droxylamine in the cells compared to the non-alkylated compound, caused by a faster degradation of the hydroxylamine or a hindered interaction between that substance and the cells. (C) 2001 Elsevier Science B.V. All rights re served.