Mutagens and carcinogens produced by the reaction of environmental aromatic compounds with nitrite. 1989

K Wakabayashi, and M Nagao, and T Sugimura
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.

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.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D009573 Nitrites Salts of nitrous acid or compounds containing the group NO2-. The inorganic nitrites of the type MNO2 (where M Nitrite
D010636 Phenols Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
D005504 Food Analysis Measurement and evaluation of the components of substances to be taken as FOOD. Analysis, Food,Analyses, Food,Food Analyses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001681 Biological Assay A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. Bioassay,Assay, Biological,Assays, Biological,Biologic Assay,Biologic Assays,Assay, Biologic,Assays, Biologic,Bioassays,Biological Assays
D013274 Stomach Neoplasms Tumors or cancer of the STOMACH. Cancer of Stomach,Gastric Cancer,Gastric Neoplasms,Stomach Cancer,Cancer of the Stomach,Gastric Cancer, Familial Diffuse,Neoplasms, Gastric,Neoplasms, Stomach,Cancer, Gastric,Cancer, Stomach,Cancers, Gastric,Cancers, Stomach,Gastric Cancers,Gastric Neoplasm,Neoplasm, Gastric,Neoplasm, Stomach,Stomach Cancers,Stomach Neoplasm
D015197 Carcinogenicity Tests Tests to experimentally measure the tumor-producing/cancer cell-producing potency of an agent by administering the agent (e.g., benzanthracenes) and observing the quantity of tumors or the cell transformation developed over a given period of time. The carcinogenicity value is usually measured as milligrams of agent administered per tumor developed. Though this test differs from the DNA-repair and bacterial microsome MUTAGENICITY TESTS, researchers often attempt to correlate the finding of carcinogenicity values and mutagenicity values. Tumorigenicity Tests,Carcinogen Tests,Carcinogenesis Tests,Carcinogenic Activity Tests,Carcinogenic Potency Tests,Carcinogen Test,Carcinogenesis Test,Carcinogenic Activity Test,Carcinogenic Potency Test,Carcinogenicity Test,Potency Test, Carcinogenic,Potency Tests, Carcinogenic,Test, Carcinogen,Test, Carcinogenesis,Test, Carcinogenic Activity,Test, Carcinogenic Potency,Test, Carcinogenicity,Test, Tumorigenicity,Tests, Carcinogen,Tests, Carcinogenesis,Tests, Carcinogenic Activity,Tests, Carcinogenic Potency,Tests, Carcinogenicity,Tests, Tumorigenicity,Tumorigenicity Test
D015538 Nitrosation Conversion into nitroso compounds. An example is the reaction of nitrites with amino compounds to form carcinogenic N-nitrosamines. Nitrosations

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