Mutagens and carcinogens produced by the reaction of environmental aromatic compounds with nitrite.
A variety of foodstuffs including soy sauce, vegetables and smoked foods showed direct-acting mutagenicity in bacteria upon nitrite treatment. From these foodstuffs, several nitrosatable mutagen precursors were isolated and their structures were found to be aromatic compounds such as phenol and indole derivatives, but not alkylamides. Many phenol and indole derivatives present in our environment were also demonstrated to form mutagenic nitrosated compounds. The direct-acting mutagenic products of phenolic compounds with nitrite were all diazo derivatives, and those from indole compounds with nitrite were N-1 and/or C-3 nitrosated products. Relatively high amounts of nitrite were necessary for the formation of diazo compounds from phenolic compounds. By contrast, indole reacted very rapidly with nitrite, even at low, physiologically feasible concentrations such as are found in the human stomach. Piperine, aminoimidazoquinoline and butylated hydroxyanisole also reacted with nitrite and produced compounds showing mutagenicity in bacteria without metabolic activation. Besides having activity in bacteria, two nitrosated products, diazo and nitrosoindole compounds, were demonstrated to be mutagenic in cultured mammalian cells. They also formed DNA adducts and induced ornithine decarboxylase and replicative DNA synthesis in rat stomach. Furthermore, the diazo compound formed from tyramine with nitrite was proved to be carcinogenic in rats.
Wakabayashi
K
K
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Nagao
M
M
Sugimura
T
T
D000818:Animals; D001681:Biological Assay; D015197:Carcinogenicity Tests; D005504:Food Analysis; D007211:Indoles / Q000032:analysis* / Q000494:pharmacology; D051379:Mice; D009152:Mutagenicity Tests; D009573:Nitrites; D015538:Nitrosation; D010636:Phenols / Q000032:analysis* / Q000494:pharmacology; D051381:Rats; D013274:Stomach Neoplasms / Q000139:chemically induced*
D007211:Indoles; D009573:Nitrites; D010636:Phenols