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.
D000632:Aminopyrine / Q000031:analogs & derivatives*; D000675:Ampyrone / Q000031:analogs & derivatives; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D000983:Antipyrine / Q000031:analogs & derivatives; D003545:Cysteine / Q000494:pharmacology*; D004177:Dipyrone / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology; D008297:Male; D009153:Mutagens / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D009602:Nitrosamines; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009153:Mutagens; D009573:Nitrites; D009602:Nitrosamines; D013438:Sulfhydryl Compounds; D000632:Aminopyrine; D000675:Ampyrone; D004177:Dipyrone; C036248:4-(N-methyl-N-nitroso)aminoantipyrine; C036249:1-diketobutyryl-1-phenyl-2-methyl-2-nitrosohydrazide; C036250:1-acetyl-1-methyl-2-nitroso-2-phenylhydrazine; D005978:Glutathione; D003545:Cysteine; D000983:Antipyrine