N- and O-acetylation of aromatic and heterocyclic amine carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS-1 cells

doi:10.1016/0006-291X(92)91703-S

Biochemical and Biophysical Research Communications

Volume 185, Issue 3, 30 June 1992, Pages 839-844

https://doi.org/10.1016/0006-291X(92)91703-S Get rights and content

Abstract

Human monomorphic and polymorphic arylamine acetyltransferases (EC 2.3.1.5) were expressed in monkey kidney COS-1 cells and used to study the N- and O-acetylation of a number of carcinogenic amines and their N-hydroxy metabolites. The monomorphic enzyme N-acetylated the aromatic amines, 2-aminofluorene and 4-aminobiphenyl, and also O-acetylated their N-hydroxy derivatives. None of the food-derived heterocyclic amines (Glu-P-1, PhIP, IQ, MeIQx) were substrates and their N-hydroxy metabolites were poorly O-acetylated by this isozyme. By contrast, the polymorphic acetyltransferase catalyzed the N-acetylation of both aromatic amines, and to a lesser extent, Glu-P-1 and PhIP. However, all six N-hydroxy amine substrates were readily O-acetylated to form DNA-bound adducts by the polymorphic isozyme. These data suggest that, for the heterocyclic amine carcinogens, rapid acetylator individuals will be predisposed to their genotoxicity.

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In humans, there are two isozymes of the N-acetyltransferases, NAT1 and NAT2. NAT1 is distributed ubiquitously throughout the body, while NAT2 is most highly expressed in the liver and intestine.8,9,46–52 Both enzymes are highly polymorphic.46,47
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N- and O-acetylation of aromatic and heterocyclic amine carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS-1 cells

Abstract

Mut. Res

Biochim. Biophys. Acta

Lancet

J. Biol. Chem

Environ. Health Perspect

CRC Crit. Rev. Toxicol

Cancer Res

Jpn. J. Cancer Res

Arch. Surg

Cancer Res