Mammalian cell mutagenicity and metabolism of heterocyclic aromatic amines.
Heterocyclic aromatic amines are bacterial mutagens which also induce DNA damage in mammalian cells. Damage has been demonstrated using a number of endpoints, including gene mutation, chromosome aberrations, sister-chromatid exchange, DNA-strand breaks, DNA repair and oncogene activation. Although the responses in mammalian cells are weak when compared to bacterial mutagenicity, heterocyclic aromatic amines are rodent carcinogens. Metabolic N-oxidation by cytochrome P450 is an initial activation step with subsequent transformation of the N-hydroxy metabolites to the ultimate mutagenic species by O-acetyltransferase or sulfotransferase. Major routes of detoxification include cytochrome P450-mediated ring oxidation followed by conjugation to glucuronic or sulfuric acid. Direct conjugation to the exocyclic amine group also occurs. Major reactions include N-glucuronidation and sulfamate formation.
Aeschbacher
H U
HU
Nestlé Research Centre, Lausanne, Switzerland.
Turesky
R J
RJ
D000588:Amines / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004249:DNA Damage; D004260:DNA Repair; D005502:Food; D006571:Heterocyclic Compounds / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008322:Mammals; D009152:Mutagenicity Tests
D000588:Amines; D006571:Heterocyclic Compounds