The pH-dependent response of Salmonella typhimurium TA100 to mutagenic N-nitrosamines.
The mutagenicity of some N-nitrosodialkylamines, i.e. N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodi-n-butylamine, N-nitrosomorpholine and N-nitrosopyrrolidine, was assayed on Salmonella typhimurium TA100 by the pre-incubation method, and the effect of changing the pH of the pre-incubation mixture was examined. Markedly higher mutagenicities were observed when the pre-incubation of bacteria with nitrosamine and S9 mix was done at pH 5.2, compared with mutagenicities observable after the pre-incubations at conventional pH 7. Pre-incubations at pH 6.2 resulted in responses of intermediate strength. With phenobarbital-induced rat S9, the ratios of mutagenic potency found by the pH 5.2 pre-incubation to that found by the pH 7.2 preincubation were 15-30 for N-nitrosodimethylamine, 5-10 for N-nitrosodiethylamine, 10-20 for N-nitrosodi-n-butylamine, 2-3 for N-nitrosomorpholine and 4-6 for N-nitrosopyrrolidine. The mutagenic potency of each nitrosamine varied with the change of S9 source. The S9 sources examined were PCB-induced rat and mouse livers, and uninduced rat and mouse livers. No exceptions were observed for these S9 preparations regarding the higher mutagenicity at pH 5 than at pH 7. It is speculated that the higher mutagenicity observed by the pH 5 pre-incubation was due to the stability of the active intermediate, alpha-hydroxynitrosodialkylamines, in weakly acidic media.
D000818:Animals; D004052:Diethylnitrosamine / Q000378:metabolism / Q000494:pharmacology; D004128:Dimethylnitrosamine / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism / Q000494:pharmacology*; D009242:N-Nitrosopyrrolidine / Q000378:metabolism / Q000494:pharmacology; D009602:Nitrosamines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects*
D009153:Mutagens; D009602:Nitrosamines; D004052:Diethylnitrosamine; C002741:N-nitrosomorpholine; C012279:dibutylnitrosamine; D004128:Dimethylnitrosamine; D009242:N-Nitrosopyrrolidine