Inhibition of the binding of 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene to DNA in mouse skin epidermis by 1-ethynylpyrene

Carcinogenesis. 1990 Jul;11(7):1139-43. doi: 10.1093/carcin/11.7.1139.

Abstract

The effects of 1-ethynylpyrene (EP), 1-vinylpyrene (VP) and 2-ethynlnaphthalene (EN) on the covalent binding of 7,12-dimethylbenz[a]anthracene (DMBA) and of benzo[a]-pyrene (B[a]P) to the epidermal DNA in mouse skin were investigated. When applied topically, 5 min before an initiating dose of 10 nmol DMBA or of 200 nmol B[a]P, EP was an effective inhibitor of the formation of the covalent complexes of these procarcinogenic polycyclic aromatic hydrocarbons (PAHs) with the epidermal DNA. VP, applied under the same conditions, was a significantly less effective inhibitor of the binding of DMBA to DNA and showed even weaker inhibition of the binding of B[a]P. EN was ineffective as an inhibitor of the binding of either DMBA or B[a]P. These results establish that both the pyrene nucleus and the ethynyl substituent of EP contribute to the effective inhibition of the binding of DMBA and B[a]P to the epidermal DNA of mouse skin. No significant changes in the ratios of the anti- to the syndiol epoxide-DNA adducts of DMBA or of B[a]P were produced by doses of EP that produced inhibitions of the binding to DNA. At doses of VP that inhibited covalent binding of both DMBA and B[a]P, no changes in DMBA-DNA adduct distributions were observed but changes in the relative proportions of several B[a]P-DNA adducts were noted. These data are discussed in terms of the potential of aryl acetylenes to act as suicide inhibitors (mechanism-based inactivators) of cytochrome P450-dependent monooxygenase isozymes.

Publication types

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

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / metabolism*
  • Administration, Topical
  • Animals
  • Benzo(a)pyrene / metabolism*
  • DNA / metabolism*
  • Dose-Response Relationship, Drug
  • Mice
  • Naphthalenes / administration & dosage
  • Naphthalenes / pharmacology
  • Pyrenes / administration & dosage
  • Pyrenes / pharmacology*
  • Skin / metabolism*

Substances

  • Naphthalenes
  • Pyrenes
  • 1-vinylpyrene
  • 2-ethynylnaphthalene
  • Benzo(a)pyrene
  • 1-ethynylpyrene
  • 9,10-Dimethyl-1,2-benzanthracene
  • DNA