N-hydroxyarylamines

Drug Metab Rev. 2002 Aug;34(3):607-23. doi: 10.1081/dmr-120005663.

Abstract

Aryl and heterocyclic amines are of particular interest because of their carcinogenicity. The N-hydroxy derivatives are formed by oxidation, usually by the cytochrome P450 (P450) enzymes and most often by P450 family 1. The mechanism of oxidation appears to resemble that of other P450 reactions. The N-hydroxy products can be conjugated to yield esters, which are unstable and form nitrenium ions. Reaction with DNA is most common at the N2 atom and particularly at the C8 atom of guanine. A mechanism involving initial formation of an N7-guanyl adduct can be utilized in explaining the C 8-guanyl adducts plus several other side reactions. The high mutagenicity of N-hydroxy heterocyclic amines in bacterial systems has provided a useful tool for the development of models useful for screening and chemoprevention and for the generation of P450 enzymes with altered properties.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amines / chemistry*
  • Amines / metabolism*
  • Amines / pharmacology
  • Base Sequence
  • Cytochrome P-450 Enzyme System / metabolism
  • DNA / chemistry
  • DNA / metabolism
  • Enzyme Activation
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Guanine / chemistry
  • Guanine / metabolism
  • Humans
  • Molecular Sequence Data
  • Molecular Structure
  • Mutagenicity Tests
  • NADPH-Ferrihemoprotein Reductase / genetics
  • NADPH-Ferrihemoprotein Reductase / metabolism
  • Oxidation-Reduction

Substances

  • Amines
  • Guanine
  • DNA
  • Cytochrome P-450 Enzyme System
  • NADPH-Ferrihemoprotein Reductase