Experimental studies on aclacinomycin

Experimental features of aclacinomycin (ACM), a new antitumour antibiotic of the anthracycline group, are presented. ACM inhibited the growth of experimental mouse tumours and human cancer xenografts from various origins. In CDF1 mice with L1210 cells treated i.p. with ACM in combination with Ara-C for 10 days, a 459% ILS was observed, including 67% of 60-day survivors. The inhibition of RNA and DNA synthesis was examined in L1210 cells. The IC50 values of ACM for incorporations of [14C]-thymidine and [14C]-uridine were 0.30 and 0.038 microgram/ml respectively. The ratio of IC50. DNA/RNA was 7.9, while with adriamycin (ADR) it was 2.5. ACM showed no mutagenic activity in the Ames' test and the rec- assay. The cardiac toxicity of ACM was significantly lower than that of ADR. Lower ECG changes, a return to normal after discontinuation of the drug and slighter ultrastructural modifications of the myocardium were demonstrated in hamsters and rabbits. When administered to hamsters i.v. at 5 mg/kg, ACM was eliminated almost completely from the heart muscle after 2 h, while ADR remained at 8 micrograms/g even after 8 h.