N-and O-acetylation of aromatic and heterocyclic amine carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS-1 cells.
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.
Minchin
R F
RF
Department of Pharmacology, University of Western Australia, Nedlands.
Reeves
P T
PT
Teitel
C H
CH
McManus
M E
ME
Mojarrabi
B
B
Ilett
K F
KF
Kadlubar
F F
FF
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
D000588:Amines; D002273:Carcinogens; D006571:Heterocyclic Compounds; D001191:Arylamine N-Acetyltransferase