Structure elucidation of a 6-methylbenzo[a]pyrene-DNA adduct formed by horseradish peroxidase in vitro and mouse skin in vivo

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Abstract

Activation of polycyclic aromatic hydrocarbons (PAH) by horseradish peroxidase (HRP) with H2O2 has been studied as a model system for one-electron oxidation. This peroxidase has been used to catalyze binding of 6-[14C]methylbenzo[a]pyrene (BP-6-CH3) to DNA, which was purified, hydrolyzed to deoxyribonucleosides and analyzed by high pressure liquid chromatography (HPLC). The predominant hydrocarbon-DNA adduct observed was identified as BP-6-CH3 bound at the 6-methyl group to the 2-amino group of dG, confirming that activation by HRP occurs by one-electron oxidation. When DNA from mouse skin treated in vivo with [14C]BP-6-CH3 was purified, hydrolyzed and analyzed by HPLC, a profile was observed which was qualitatively similar to that from the peroxidase system. In particular, the identified adduct with the hydrocarbon bound at the 6-methyl group to the 2-amino group of dG was obtained. These results demonstrate that one-electron oxidation is the mechanism of activation by HRP for aromatic hydrocarbons and indicate that the same mechanism may occur in mouse skin, a target tissue for hydrocarbon carcinogenesis.

Original languageEnglish (US)
Pages (from-to)111-122
Number of pages12
JournalChemico-Biological Interactions
Volume47
Issue number1
DOIs
StatePublished - Oct 15 1983

Keywords

  • Carcinogenic activation
  • DNA adduct structure
  • Horseradish peroxidase
  • Mouse skin
  • One-electron oxidation
  • Polycyclic aromatic hydrocarbons

ASJC Scopus subject areas

  • Toxicology

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