title: N-and O-acetylation of aromatic and heterocyclic amine carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS-1 cells.
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.
authors.affiliation: Department of Pharmacology, University of Western Australia, Nedlands.
authors.forename: R F
authors.initials: RF
authors.lastname: Minchin
authors.forename: P T
authors.initials: PT
authors.lastname: Reeves
authors.forename: C H
authors.initials: CH
authors.lastname: Teitel
authors.forename: M E
authors.initials: ME
authors.lastname: McManus
authors.forename: B
authors.initials: B
authors.lastname: Mojarrabi
authors.forename: K F
authors.initials: KF
authors.lastname: Ilett
authors.forename: F F
authors.initials: FF
authors.lastname: Kadlubar
mesh_terms: D000107:Acetylation; D000588:Amines / Q000138:chemical synthesis / Q000378:metabolism*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D002460:Cell Line; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D013379:Substrate Specificity; D014162:Transfection
chemical_list: D000588:Amines; D002273:Carcinogens; D006571:Heterocyclic Compounds; D001191:Arylamine N-Acetyltransferase