Effect of 7-Hydroxybenzo[a]pyrene on Benzo[a]pyrene Metabolism and Formation of DNA Adducts

Prabhakar Devanesan, Rosa Todorovic, Eleanor G Rogan, Ercole Cavalieri

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Two major pathways are responsible for the metabolic activation of benzo[a]pyrene (BP) and other aromatic hydrocarbons, one leading to radical cations and the other to diol epoxides. It has been suggested that 7-hydroxyBP (7-OHBP) might inhibit formation of diol epoxides. We have examined the effect of various concentrations of 7-OHBP on the cytochrome P450-catalyzed metabolism of BP, total DNA binding and formation of BP-DNA adducts. Metabolism of BP was not significantly affected by 7-OHBP. Both total BP-DNA binding and stable DNA adducts, as measured by the 32P-postlabeling method, were inhibited in a concentration-dependent manner, ranging from 25% to 72% inhibition for binding and 23% to 85% for adducts at 7-OHBP:BP ratios of 0.1 to 1.0. Formation of the depurination adducts of BP was inhibited 67% to 100% at a molar ratio of 1:0.25 (BP:7-OHBP), whereas none of the depurination adducts were detected at a molar ratio of 1:0.5 (BP:7-OHBP). These results suggest that 7-OHBP is not a selective inhibitor of the BP diol epoxide pathway, but a potent inhibitor of total DNA adduct formation.

Original languageEnglish (US)
Pages (from-to)111-118
Number of pages8
JournalPolycyclic Aromatic Compounds
Volume6
Issue number1-4
DOIs
StatePublished - Jan 1994

Fingerprint

DNA Adducts
Benzo(a)pyrene
Epoxy Compounds
Pyrene
Metabolism
DNA
Aromatic Hydrocarbons
Aromatic hydrocarbons
Cytochrome P-450 Enzyme System
Cations
Positive ions
Chemical activation
pyrene

Keywords

  • 7-hydroxybenzo[a]pyrene
  • DNA adducts
  • Metabolism
  • diol epoxide
  • inhibitory effect
  • radical cation

ASJC Scopus subject areas

  • Polymers and Plastics
  • Organic Chemistry
  • Materials Chemistry

Cite this

Effect of 7-Hydroxybenzo[a]pyrene on Benzo[a]pyrene Metabolism and Formation of DNA Adducts. / Devanesan, Prabhakar; Todorovic, Rosa; Rogan, Eleanor G; Cavalieri, Ercole.

In: Polycyclic Aromatic Compounds, Vol. 6, No. 1-4, 01.1994, p. 111-118.

Research output: Contribution to journalArticle

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