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Binding of benzo(a)pyrene metabolites to cellular DNA in perfused rat lungs

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Summary

The influence of pretreatment with monooxygenase inducers on total irreversible binding of metabolically activated [3H]-benzo(a)pyrene to cellular DNA and the formation of benzo(a)pyrene metabolite-deoxyribonucleoside adducts after cytochrome P-448 induction was studied in perfused rat lungs. Pretreatment with the cytochrome P-448 inducer β-naphthoflavone increasing binding by a factor of 23. In lungs of induced animals, 0.45 pmoles of benzo(a)pyrene equivalents were bound per mg DNA. Binding to RNA and to protein was also considerably induced by β-naphthoflavone. Phenobarbital treatment did not significantly increase binding to cellular macromolecules of rat lung. Analysis of hydrolyzed DNA of lungs from β-naphthoflavone-treated rats by Sephadex LH 20 chromatography revealed the formation of at least two nucleoside adducts with metabolically activated benzo(a)pyrene one of which is probably due to modification of the DNA with a benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide and the other to modification of DNA with secondary metabolites of benzo(a)pyrene phenols.

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Authors and Affiliations

  1. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, D-6500, Mainz, Federal Republic of Germany

    B. Deckers-Schmelzle, E. Klaus, R. Kahl & G. F. Kahl

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  1. B. Deckers-Schmelzle
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  2. E. Klaus
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  3. R. Kahl
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  4. G. F. Kahl
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Additional information

This study was supported by the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg.

In part subject of the doctoral thesis of Erik Klaus, Fachbereich Biologie, University of Mainz.

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Deckers-Schmelzle, B., Klaus, E., Kahl, R. et al. Binding of benzo(a)pyrene metabolites to cellular DNA in perfused rat lungs. Naunyn-Schmiedeberg's Arch. Pharmacol. 303, 303–307 (1978). https://doi.org/10.1007/BF00498059

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  • DOI: https://doi.org/10.1007/BF00498059

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