Mammalian cell mutagenicity and metabolism of heterocyclic aromatic amines.
AI Summary
Key Findings
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.
Affiliation
Nestlé Research Centre, Lausanne, Switzerland.
External References
- PubMed ID:
- 2017210
Comments
Sign in or create a free account to join the conversation.
Sign in to commentBe the first to comment.