Comparative microscopic study of cardiotoxicity and skin toxicity of anthracycline analogs

Golden hamsters were submitted, three times a week during 4 weeks, to i.p. administration of an antracenedione, mitoxantrone (MTX), and 12 different anthracyclines, adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (e-ADM), rubidazone (RBZ), aclacinomycin (ACM), N-trifluoroacetyladriamycin-14-valerate (AD-32), tetrahydropyranyl-adriamycin (THP-ADM), N-L-leucyl-daunorubicin (l-DNR), carminomycin (CAM), rubicyclamin (RBC) and N-trifluoroacetyl-adriamycin-14-9-hemiadipate (AD-143), at doses equivalent to 3/4 those which are optimally oncostatic on murine L1210 leukemia. The electron microscopic (EM) study of the myocardium showed that all studied drugs are cardiotoxic, but with different degree of cardiotoxicity. The histopathological study of the skin detect degenerative lesions with different degree of alopecia. According to the degree of their cardiotoxicity, skin toxicity, and general toxicity or mortality, all drugs studied are classified into 3 groups: 1st group, ADM, DNR, 1-DNR and RBZ, causing very severe cardiac alterations and alopecia (grade 2-3), and very high mortality, 2nd group, e-ADM, DTR, CAM RBC and MTX, with less severe cardiac alterations, and alopecia (grade 1-2), and always high mortality, and 3rd group, ACM, THP-ADM, AD-32 and AD-143, causing less severe myocardial alterations (grade 1-2), without alopecia (grade 0), and extremely low mortality and general toxicity.