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

Aurora Viaje, Jui Yun L Lu, Nancy Eddy Hopkins, Anusha N. Nettikumara, John DiGiovanni, William L. Alworth, Thomas J Slaga

Research output: Contribution to journalArticle

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Abstract

The effects of 1-ethynylpyrene (EP), 1-vinylpyrene (VP) and 2-ethynylnaphthalene (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.

Original languageEnglish (US)
Pages (from-to)1139-1143
Number of pages5
JournalCarcinogenesis
Volume11
Issue number7
StatePublished - Jul 1990
Externally publishedYes

Fingerprint

9,10-Dimethyl-1,2-benzanthracene
Epidermis
Anthracene
Benzo(a)pyrene
Pyrene
Skin
Mouse
DNA
Inhibitor
Dose
Alkynes
Polycyclic Aromatic Hydrocarbons
Epoxy Compounds
Mixed Function Oxygenases
Cytochrome P-450 Enzyme System
Suicide
Isoenzymes
Acetylene
Hydrocarbons
Polycyclic aromatic hydrocarbons

ASJC Scopus subject areas

  • Cancer Research
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience

Cite this

Viaje, A., Lu, J. Y. L., Hopkins, N. E., Nettikumara, A. N., DiGiovanni, J., Alworth, W. L., & Slaga, T. J. (1990). Inhibition of the binding of 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene to DNA in mouse skin epidermis by 1-ethynylpyrene. Carcinogenesis, 11(7), 1139-1143.

Inhibition of the binding of 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene to DNA in mouse skin epidermis by 1-ethynylpyrene. / Viaje, Aurora; Lu, Jui Yun L; Hopkins, Nancy Eddy; Nettikumara, Anusha N.; DiGiovanni, John; Alworth, William L.; Slaga, Thomas J.

In: Carcinogenesis, Vol. 11, No. 7, 07.1990, p. 1139-1143.

Research output: Contribution to journalArticle

Viaje, A, Lu, JYL, Hopkins, NE, Nettikumara, AN, DiGiovanni, J, Alworth, WL & Slaga, TJ 1990, 'Inhibition of the binding of 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene to DNA in mouse skin epidermis by 1-ethynylpyrene', Carcinogenesis, vol. 11, no. 7, pp. 1139-1143.
Viaje A, Lu JYL, Hopkins NE, Nettikumara AN, DiGiovanni J, Alworth WL et al. 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):1139-1143.
Viaje, Aurora ; Lu, Jui Yun L ; Hopkins, Nancy Eddy ; Nettikumara, Anusha N. ; DiGiovanni, John ; Alworth, William L. ; Slaga, Thomas J. / Inhibition of the binding of 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene to DNA in mouse skin epidermis by 1-ethynylpyrene. In: Carcinogenesis. 1990 ; Vol. 11, No. 7. pp. 1139-1143.
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abstract = "The effects of 1-ethynylpyrene (EP), 1-vinylpyrene (VP) and 2-ethynylnaphthalene (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.",
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