Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: a review

Toxicol Appl Pharmacol. 2005 Aug 1;206(1):73-93. doi: 10.1016/j.taap.2004.11.006. Epub 2005 Jan 8.


Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic compounds (HACs) constitute a major class of chemical carcinogens present in the environment. These compounds require activation to electrophilic metabolites to exert their mutagenic or carcinogenic effects. There are three principal pathways currently proposed for metabolic activation of PAH and HAC: the pathway via bay region dihydrodiol epoxide by cytochrome P450 enzymes (CYPs), the pathway via radical cation by one-electron oxidation, and the ortho-quinone pathway by dihydrodiol dehydrogenase (DD). In addition to these major pathways, a brief description of a minor metabolic activation pathway, sulfonation, for PAHs that contain a primary benzylic alcoholic group or secondary hydroxyl group(s) is included in this review. The DNA damages caused through the reactive metabolites of PAH/HAC are described involving the DNA covalent binding to form stable or depurinating adducts, the formation of apurinic sites, and the oxidative damage. The review emphasizes the chemical/biochemical reactions involved in the metabolic processes and the chemical structures of metabolites and DNA adducts.

Publication types

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

MeSH terms

  • Animals
  • Biotransformation
  • Carcinogens / metabolism*
  • Carcinogens / pharmacokinetics
  • DNA Adducts / biosynthesis*
  • Epoxy Compounds / chemical synthesis
  • Epoxy Compounds / metabolism*
  • Epoxy Compounds / pharmacokinetics
  • Heterocyclic Compounds / metabolism*
  • Heterocyclic Compounds / pharmacokinetics
  • Polycyclic Aromatic Hydrocarbons / metabolism*
  • Polycyclic Aromatic Hydrocarbons / pharmacokinetics
  • Stereoisomerism
  • Structure-Activity Relationship


  • Carcinogens
  • DNA Adducts
  • Epoxy Compounds
  • Heterocyclic Compounds
  • Polycyclic Aromatic Hydrocarbons