Mammalian cell mutagenicity and metabolism of heterocyclic aromatic amines

Hans Ulrich Aeschbacher, Robert J. Turesky

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)235-250
Number of pages16
JournalMutation Research/Genetic Toxicology
Volume259
Issue number3-4
DOIs
StatePublished - Jan 1 1991

Keywords

  • Adduct formation
  • Bacterial transformation
  • Genotoxicity
  • Heterocyclic aromatic amines
  • Metabolism
  • N-Oxidation

Fingerprint

Dive into the research topics of 'Mammalian cell mutagenicity and metabolism of heterocyclic aromatic amines'. Together they form a unique fingerprint.

Cite this