Correlations between cytotoxicity, biochemical effects, drug levels, and therapeutic effectiveness of daunomycin and adriamycin on Sarcoma 180 ascites in mice.

The effects of adriamycin and daunomycin on mitotic activity, nucleic acid synthesis, and proliferative activity have been compared in Sarcoma 180 ascites in mice and related to the uptake and retention of the drugs by the ascites cells. The half-life of the drug in the cells after a single injection was 4 hr for daunomycin and 12 hr for adriamycin, while after repeated doses the uptake of the antibiotics was similar. The inhibition of mitotic activity and of thymidine incorporation into DNA was similar with daunomycin and adriamycin, while adriamycin inhib ited uridine incorporation into RNA to a greater extent. When given according to different schedules to Sarcoma 180-bearing mice, adriamycin appeared able to inhibit tumor growth to a greater extent than did daunomycin and to induce a greater number of tumor-free long-term survi vors. This effect has been observed also after a treatment schedule which results in similar intracellular levels of both antibiotics. The importance of mechanisms other than different cellular uptake of the drugs, operative in determin ing differences in the overall therapeutic efficacy in vivo, remains to be elucidated.