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[Cancer Research 60, 1789-1792, April 1, 2000]
© 2000 American Association for Cancer Research


Advances in Brief

Acute Doxorubicin Cardiotoxicity Involves Cardiomyocyte Apoptosis1

Olli J. Arola, Antti Saraste, Kari Pulkki, Markku Kallajoki, Martti Parvinen and Liisa-Maria Voipio-Pulkki2

Departments of Medicine [O. J. A., L-M. V-P.], Anatomy [A. S., M. P.], Clinical Chemistry [K. P.], and Pathology [M. K.], University of Turku, FIN-20521 Turku, Finland

Despite well-documented cardiotoxic effects, doxorubicin remains a major anticancer agent. To study the role of myocardial apoptosis following doxorubicin administration, male Wistar rats were exposed to 1.25, 2.5, and 5 mg/kg of i.p. doxorubicin and terminated on days 1–7 in groups of five. Doxorubicin caused a significant (P < 0.001) and dose-dependent induction of cardiomyocyte apoptosis at 24–48 h after the injection. Repeated injections of 2.5 mg/kg given every other day resulted in peaks of apoptosis at 24 h after each injection. However, no additive effect of repeated dosing was noted. In histological samples, alterations in the cytoskeletal apparatus with focal loss of contractile elements were seen after a single injection. Myocyte necrosis was absent. Thus, acute doxorubicin-induced cardiotoxicity involves cardiomyocyte apoptosis, a potentially preventable form of myocardial tissue loss.




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