Mutagenicity of N-nitroso compounds formed by the reaction of sulpyrine with nitrite; effects of cysteine and its derivatives.

Cysteine and its derivatives were tested for their effect on the mutagenic activities of nitrosation products of sulpyrine, 1-diketo-butyryl-1-phenyl-2-methyl-2-nitrosohydrazide hydrate (DPMN) and 4-(N-methyl-N-nitroso)aminoantipyrine (MNAA), using Salmonella typhimurium TA100. The addition of cysteine, cysteamine, cysteine methyl ester, glutathione, 2-mercaptoethanol and homocysteine to the mixture of DPMN and bacteria before pre-incubation markedly increased the mutagenic activity of DPMN in the absence of rat-liver microsomal preparation (S9 mix). An approximately thirty-fold increase in the number of revertants was caused by the addition of cysteine at a concentration of 3 mmol/1. Studies of the structure-activity relationship suggest that a thiol group is necessary in order that the compounds exhibit the enhancing effect and that the thiol compounds having an amino group at the beta-position are more active than the others. Both cysteine and glutathione were rather inhibitory in the development of mutagenesis by MNAA in the presence of S9 mix.