Acute anthracycline cardiotoxicity. Comparative morphologic study of three analogues

A. L. Taylor, M. M. Applefeld, P. H. Wiernik, L. B. Grochow, L. C. Mader, B. H. Bulkley

Research output: Contribution to journalArticle

Abstract

Chemotherapeutic use of anthracycline antibiotics is limited by their cardiotoxic effects. A potential solution to this problem is the development of anthracycline analogues retaining antitumor efficacy but without cardiac toxicity. An isolated perfused rabbit heart model was used to compare the nature and extent of early ultrastructural effects on the myocyte of three anthracycline analogues purported to have lesser cardiotoxicity than Adriamycin (doxorubicin). Seventeen rabbit hearts were perfused with oxygenated Krebs-Ringer bicarbonate buffer at 39° C containing either Adriamycin (4 mg/L), daunomycin (10.6 mg/L), aclacinomycin (8 mg/L), or rubidazone (17.6 mg/L). For comparison, three hearts each were exposed to phosphoramide mustard (14.7 mg or 25 mg/L), or 4-hydroperoxy cyclophosphamide (24 mg or 17 mg/L), two active congeners of cyclophosphamide, an agent interacting with DNA differently than the anthracyclines and which is known to be cardiotoxic in high dose. Two hearts were exposed to dactinomycin 0.1 mg or 0.2 mg/L) which intercalates with DNA in a manner similar to anthracyclines but which is not cardiotoxic. Ten control hearts were perfused with oxygenated buffer solution only. Light microscopic study disclosed no differences between treated and control hearts. Electron microscopic examination showed a striking and distinctive clumping of nuclear chromatin with clearing of chromatin from the nuclear membrane in all anthracycline treated hearts but in no hearts treated with 4-hydroperoxy cyclophosphamide, phosphoramide mustard, dactinomycin, or control hearts. The nuclear effects of the four anthracycline analogues were indistinguishable. Thus, all anthracycline analogues studied produced acute nuclear alterations which were distinctive from the changes produced by other DNA interactive chemotherapeutic agents. The relationship of the distinctive anthracycline nuclear changes to the late cardiomyopathy requires further definition.

Original languageEnglish (US)
Pages (from-to)1660-1666
Number of pages7
JournalCancer
Volume53
Issue number8
StatePublished - 1984
Externally publishedYes

Fingerprint

Anthracyclines
Doxorubicin
Cyclophosphamide
Dactinomycin
Chromatin
DNA
Buffers
Rabbits
Cardiotoxicity
Daunorubicin
Nuclear Envelope
Bicarbonates
Cardiomyopathies
Muscle Cells
Electrons
Anti-Bacterial Agents
Light

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Taylor, A. L., Applefeld, M. M., Wiernik, P. H., Grochow, L. B., Mader, L. C., & Bulkley, B. H. (1984). Acute anthracycline cardiotoxicity. Comparative morphologic study of three analogues. Cancer, 53(8), 1660-1666.

Acute anthracycline cardiotoxicity. Comparative morphologic study of three analogues. / Taylor, A. L.; Applefeld, M. M.; Wiernik, P. H.; Grochow, L. B.; Mader, L. C.; Bulkley, B. H.

In: Cancer, Vol. 53, No. 8, 1984, p. 1660-1666.

Research output: Contribution to journalArticle

Taylor, AL, Applefeld, MM, Wiernik, PH, Grochow, LB, Mader, LC & Bulkley, BH 1984, 'Acute anthracycline cardiotoxicity. Comparative morphologic study of three analogues', Cancer, vol. 53, no. 8, pp. 1660-1666.
Taylor AL, Applefeld MM, Wiernik PH, Grochow LB, Mader LC, Bulkley BH. Acute anthracycline cardiotoxicity. Comparative morphologic study of three analogues. Cancer. 1984;53(8):1660-1666.
Taylor, A. L. ; Applefeld, M. M. ; Wiernik, P. H. ; Grochow, L. B. ; Mader, L. C. ; Bulkley, B. H. / Acute anthracycline cardiotoxicity. Comparative morphologic study of three analogues. In: Cancer. 1984 ; Vol. 53, No. 8. pp. 1660-1666.
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