Format

Send to

Choose Destination
Cancer Lett. 1999 Sep 1;143(2):167-71.

Detoxification of carcinogenic aromatic and heterocyclic amines by enzymatic reduction of the N-hydroxy derivative.

Author information

1
Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, AR 72079-9501, USA.

Abstract

The metabolic activation pathways associated with carcinogenic aromatic and heterocyclic amines have long been known to involve N-oxidation, catalyzed primarily by cytochrome P4501A2, and subsequent O-esterification, often catalyzed by acetyltransferases (NATs) and sulfotransferases (SULTs). We have found a new enzymatic mechanism of carcinogen detoxification: a microsomal NADH-dependent reductase that rapidly converts the N-hydroxy arylamine back to the parent amine. The following N-OH-arylamines and N-OH-heterocyclic amines were rapidly reduced by both human and rat liver microsomes: NOH-4-aminoazobenzene, N-OH-4-aminobiphenyl (N-OH-ABP), N-OH-aniline, N-OH-2-naphthylamine, N-OH-2-aminofluorene, N-OH-4,4'-methylenebis(2-chloroaniline) (N-OH-MOCA), N-OH-1-naphthyamine, N-OH-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), N-OH-2-amino-alpha-carboline (N-OH-AalphaC), N-OH-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (N-OH-MeIQx), and N-OH-2-amino-3-methylimidazo[4,5-f]quinoline (N-OH-IQ). In addition, primary rat hepatocytes and human HepG2 cells efficiently reduced N-OH-PhIP to PhIP. This previously unrecognized detoxification pathway may limit the bioavailability of carcinogenic N-OH heterocyclic and aromatic amines for further activation, DNA adduct formation, and carcinogenesis.

PMID:
10503898
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center