Title

Pathologic effects of adriamycin (NSC 123127) in experimental systems

Document Type

Article

Publication Date

1-1-1975

Abstract

Although this review considers some of the more infrequently occurring or unusual histocytopathic effects of adriamycin, it is imperative to mention that myelosuppression, stomatitis, and digestive disturbances are the major clinical toxic effects of adriamycin in patients. The reported incidence of adriamycin induced cardiotoxicity varies from 1% to 30% depending upon the total cumulative dose administered. In vitro and in vivo studies of the cytotoxic effects of adriamycin have contributed to a better understanding of its mechanism of action on normal and neoplastic cells. Numerous pharmacologic and toxicologic investigations have been performed using various animal species. Since the first report in the U.S.A. of the cardiotoxic effects of daunorubicin in 1969, investigators have undertaken a search for an animal model with a cardiotoxic syndrome similar to that reported in man. An animal model could be used to test analogs of adriamycin for cardiotoxic potential, to test antidotal procedures, and to study the pathogenesis of the drug induced cardiomyopathy. Current evidence suggests that the rabbit, monkey rat, mouse and hamster develop characteristic, delayed, dose related, myocardial changes in response to adriamycin administration. Only the rabbit and monkey have been reported to exhibit a congestive heart failure syndrome associated with the cardiomyopathy. Characteristic myocardial lesions include vacuolization, edema, myocytolysis, and fibrosis. Ultrastructural changes have been described in nuclear, myofibrillar, mitochondrial, and sarcotubular organelles. The end result is a complete destruction and lysis of individual cardiac myocytes with replacement fibrosis. The pathogenetic mechanism(s) of the adriamycin induced cardiotoxicity appears to be multifactorial, involving biochemical and morphologic lesions of the myocardium. Experimental animals appear to be sensitive to the nephrotoxic effects of adriamycin, whereas altered renal function or morphology in patients is rare. An additional adriamycin induced toxic effect that has not been reported in man is impairment of chondro osteogenesis. Animal studies have revealed an infrequent carcinogenic effect which has not been reported in man. Hyperpigmentation, allergic reactions, and anaphylaxis have been reported to occur in association with adriamycin treatment. Further studies are required to elucidate the mechanisms involved in the development of these interesting, albeit infrequent, histocytopathologic and biochemical adverse effects of adriamycin.

Publication Source (Journal or Book title)

CANCER CHEMOTHER.REP.

First Page

159

Last Page

175

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