Skip to main content
SpringerLink
Log in

Adriamycin and daunomycin dose-dependent effects upon contractions of isolated rat myocytes

  • Original Articles
  • Adriamycin, Daunomycin
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Summary

Chemotherapeutic usefulness of adriamycin (ADR) and daunomycin (DAU), members of a large class of antitumor anthracyclines, is limited by a unique cardiotoxicity. Using spontaneously beating isolated myocytes from adult rat hearts, we have observed a relatively unique effect of these agents upon maximal contraction times. ADR and DAU induce cessation of beating in an identical dose-dependent manner, while two related anthracyclines exhibit similar inhibitory effects but at different concentrations. Other cytotoxic and antitumor agents tested failed to significantly affect maximal contraction times. This system may be useful in the evaluation of anthracycline analogs for cardiotoxic potential relative to ADR and DAU, as well as in studying the mechanisms of that toxicity. It may also prove useful in selective examination of the direct effects of other agents upon myocardial cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Berry MN, Friend DS, Scheuer J (1970) Morphology and metabolism of intact muscle cells isolated from adult rat heart. Circ Res 26: 679

    Google Scholar 

  2. Blum RH, Carter SK (1974) Adriamycin, a new anticancer drug with significant clinical activity. Ann Intern Med 80: 249

    Google Scholar 

  3. Carlson EC, Grosso DS, Romero SA, Frangakis CJ, Byus CV, Bressler R (1978) Ultrastructural studies of metabolically active isolated adult rat heart myocytes. J Mol Cell Cardiol 10: 449

    Google Scholar 

  4. Ferrero ME, Ferrero E, Gaga G, Bernelli-Zazzera A (1976) Adriamycin: Energy metabolism and mitochondrial oxidations in the heart of treated rabbits. Biochem Pharmacol 25: 125

    Google Scholar 

  5. Formelli F, Zedeck MS, Sternberg SS, Philips FS (1978) Effects of adriamycin on DNA synthesis in mouse and rat heart. Cancer Res 38: 3286

    Google Scholar 

  6. Grosso DS, Frangakis CJ, Carlson EC, Bressler R (1977) Isolation and characterization of myocytes from the adult rat heart. Prep Biochem 7: 383

    Google Scholar 

  7. Guarino AM, Rozencweig M, Kline I, Penta JS, Venditti JM, Lloyd HH, Holzworth DA, Muggia FM (1979) Adequacies and inadequacies in assessing murine toxicity data with antineoplastic agents. Cancer Res 39: 2204

    Google Scholar 

  8. Guarino AM (1980) Animal models for predicting cardiotoxicity. In: Nelson JD, Grassi C (eds) Current chemotherapy and infectious disease, vol II. American Society of Microbiology, Washington DC, pp 1470–1471

    Google Scholar 

  9. Henderson IC, Frei E III (1979) Adriamycin and the heart. N Engl J Med 300: 310

    Google Scholar 

  10. Inaba M, Johnson RK (1978) Uptake and retention of adriamycin and daunorubicin by sensitive and anthracycline-resistent sublines of P388 leukemia. Biochem Pharmacol 27: 2123

    Google Scholar 

  11. Iwamoto Y, Hansen IL, Porter TH, Folkers K (1974) Inhibition of coenzyme Q10-enzymes, succinoxidase and NADH-oxidase by adriamycin and other quinones having antitumor activity. Biochem Biophys Res Commun 58: 633

    Google Scholar 

  12. Lampidis TJ, Moreno G, Salet C, Vinzens F (1979) Nuclear and mitochondrial effects of adriamycin in singly isolated pulsating myocardial cells. J Mol Cell Cardiol 11: 415

    Google Scholar 

  13. Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA (1973) A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 32: 302

    Google Scholar 

  14. Lenaz L, Page JA (1976) Cardiotoxicity of adriamycin and related anthracyclines. Cancer Treat Rev 3: 111

    Google Scholar 

  15. Lenaz L, Necco A, Dasdia T, DiMarco A (1974) Biologic activity of some adriamycin (NSC-123127) derivatives. Cancer Chemother Rep [1] 58: 769

    Google Scholar 

  16. Meyers CE, McGuire WP, Liss RH, Ifrim I, Grotzinger K, Young RC (1977) Adriamycin: The role of lipid peroxidation in cardiac toxicity and tumor response. Science 197: 165

    Google Scholar 

  17. Olson HM, Young DM, Prieur DJ, LeRoy AF, Reagan RL (1974) Electrolyte and morphologic alterations of myocardium in adriamycin-treated rabbits. Am J Pathol 77: 439

    Google Scholar 

  18. Rosenoff SH, Brooks E, Bostick F, Young RC (1975) Alterations in DNA synthesis in cardiac tissue induced by adriamycin in vivo — relationship to fatal toxicity. Biochem Pharmacol 24: 1898

    Google Scholar 

  19. Ross WE, Glaubiger D, Kohn KW (1979) Qualitative and quantitative aspects of intercalator-induced DNA strand breaks. Biochim Biophys Acta 562: 41

    Google Scholar 

  20. Seraydarian MW, Artaza L (1979) Modification by adenosine of the effect of adriamycin on myocardial cells in culture. Cancer Res 39: 2940

    Google Scholar 

  21. Smith CG, Grady JE, Northam JI (1973) Relationship between cytotoxicity in vitro and whole animal toxicity. Cancer Chemother Rep 30: 9

    Google Scholar 

  22. Vahouny GV, Wei R, Starkweather R, Davis C (1970) Preparation of beating heart cells from adult rats. Science 167: 1616

    Google Scholar 

  23. Villani F, Piccinini F, Merelli P, Favalli L (1978) Influence of adriamycin on calcium exchangeability in cardiac muscle and its modification by ouabain. Biochem Pharmacol 27: 985

    Google Scholar 

  24. Von Hoff DD, Layard MW, Basa P, Davis HL, Von Hoff AL, Rozencweig M, Muggia FM (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91: 710

    Google Scholar 

  25. Young DM (1975) Pathologic effects of adriamycin (NSC-123127) in experimental systems. Cancer Chemother Rep [3] 6: 159

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Chemical Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, 20205, Bethesda, Maryland, USA

    Michael C. Lowe & Joan I. Smallwood

Authors
  1. Michael C. Lowe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joan I. Smallwood
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lowe, M.C., Smallwood, J.I. Adriamycin and daunomycin dose-dependent effects upon contractions of isolated rat myocytes. Cancer Chemother. Pharmacol. 5, 61–65 (1980). https://doi.org/10.1007/BF00578564

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00578564

Keywords

Search

Navigation