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Covalent protein binding of reactive adriamycin metabolites in rat liver and rat heart microsomes

  • Original Papers
  • Experimental Oncology
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Summary

Covalent binding of 3H-labeled adriamycin metabolites to bovine serum albumin and microsomal protein is demonstrated in an aerobic incubation system with rat liver and rat heart microsomes, respectively, using exhaustive organic solvent extraction and gel chromatography. Covalent protein binding was dependent on active microsomes, NADPH, and oxygen and was inhibited by reduced glutathione and other sulfhydryl compounds. The anthracycline moiety was spectrophotometrically evidenced in the adriamycin metabolite(s) covalently bound to protein. Thus, enzymatic activation of adriamycin in the heart with consecutive covalent protein binding of reactive adriamycin semiquinone radicals may contribute to adriamycin cardiotoxicity.

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Authors and Affiliations

  1. Dept. of Internal Medicine (Cancer Research), West German Tumor Center, University of Essen Medical School, Hufelandstraße 55, D-4300, Essen 1, Germany

    M. E. Scheulen, Anne Nienhaus & C. G. Schmidt

  2. Sect. on Pharmacology, Medical Institute of Environmental Hygiene, University of Düsseldorf, Gurlittstraße 53, D-4000, Düsseldorf 1, Germany

    H. Kappus

Authors
  1. M. E. Scheulen
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  2. H. Kappus
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  3. Anne Nienhaus
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  4. C. G. Schmidt
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Supported by the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg (FRG), SFB 102, Teilprojekt C4

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Scheulen, M.E., Kappus, H., Nienhaus, A. et al. Covalent protein binding of reactive adriamycin metabolites in rat liver and rat heart microsomes. J Cancer Res Clin Oncol 103, 39–48 (1982). https://doi.org/10.1007/BF00410304

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  • DOI: https://doi.org/10.1007/BF00410304

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