Mutagenicity of reaction products of sulpyrine with nitrite

The mutagenicity of three N-nitroso compounds produced by the reaction of sulpyrine with nitrite, 1-diketobutyryl-1-phenyl-2-methyl-2-nitrosohydrazide hydrate (DPMN), 4-(N-methyl-N-nitroso) aminoantipyrine (MNAA) and 1-acetyl-1-methyl-2-nitroso-2-phenylhydrazine, was tested on Salmonella typhimurium TA100 and TA98. The mutagenicity of related compounds, 4-methyl-aminoantipyrine, 1-acetyl-1-methyl-2-phenylhydrazine, 4-hydroxyantipyrine, sulpyrine and sodium nitrite was also examined. DPMN and MNAA, which are main reaction products in the nitrosation of sulpyrine, and sodium nitrite were mutagenic to TA100, but not to TA98. The other compounds were not mutagenic to either strain. MNAA required metabolic activation with rat-liver microsomal preparation (S9 mix) for the mutagenic activity, while DPMN did not require S9 mix. The mutagenicity of DPMN was remarkably increased by the addition of L-cysteine or glutathione. The enhancing effect was proportional to the concentrations of cysteine (0.4-2.1 mumoles/plate) or glutathione (0.8-6.5 mumoles/plate) added.