Ultrastructural study of the cardiotoxicity and light-microscopic findings of the skin after treatment of golden hamsters with seven different anthracyclines

Abstract

Golden hamsters were administered seven anthracyclines: adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (eADM), rubidazone (RBZ), aclacinomycin (ACM), and N-trifluoroacetyladriamycin-14-valerate (AD-32), three times a week during 4 weeks, at doses equivalent to 3/4 of those which are optimally oncostatic on murine L1210 leukemia. We examined their myocardia by electron microscopy (EM) and their skin by light microscopy (LM), and report here the findings of these two examinations. The mortality was very high for the groups of hamsters treated with ADM, DTR, DRB, eADM, and RBZ (all treated hamsters died before the end of the fourth week) and very low for those treated with ACM and AD-32 (for each drug, only one of the 21 treated animals died after 4 weeks of treatment). After the first week of treatment and chiefly after the second week, all treated hamsters, except those treated with ACM, showed very severe EM alterations of their myocardia. EM detected almost no early myocardial lesions in ACM-treated hamsters but, after 4 weeks of treatment, severe cardiac lesions also appeared which, like those after AD-32, were nonlethal and reversible. LM of the skin detected degenerative lesions with atrophy of all epidermic layers and a loss of the hair (alopecia) in all treated hamsters except those treated with ACM and AD-32; the skin in these two groups preserved its normal histologic structure. These observations agree with phase I-II clinical ACM studies in which the rate of ECG abnormalities was 4.5% and the rate of alopecia 0%, and with an early AD-32 clinical study conducted by Blum [3].