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

Biochem Biophys Res Commun. 1992 Jun 30;185(3):839-44. doi: 10.1016/0006-291x(92)91703-s.


Human monomorphic and polymorphic arylamine acetyltransferases (EC 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.

MeSH terms

  • Acetylation
  • Amines / chemical synthesis
  • Amines / metabolism*
  • Animals
  • Arylamine N-Acetyltransferase / genetics
  • Arylamine N-Acetyltransferase / metabolism*
  • Carcinogens / metabolism*
  • Cell Line
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / metabolism*
  • Humans
  • Kinetics
  • Substrate Specificity
  • Transfection*


  • Amines
  • Carcinogens
  • Heterocyclic Compounds
  • Arylamine N-Acetyltransferase