Article révisé par les pairs
Résumé : The complex formed between adriamycin and DNA possesses the physicochemical and in vitro biological characteristics of a lysosomotropic drug. Adriamycin is resistant to lysosomal hydrolases and binds firmly to high molecular weight DNA. When linked to DNA, adriamycin looses its properties of fluorescence, of dialysis and its antibiotic activity. Adriamycin can however be released from the complex and recovers all its properties after digestion of the DNA by lysosomal desoxyribonucleases. The adriamycin-DNA complex is two times less toxic than free adriamycin when given intraperitoneally or intravenously on five consecutive days in NMRI mice. While two times less toxic than free adriamycin, adriamycin-DNA possesses higher chemotherapic efficiency against the L1210 Leukemia in DBA2 mice. If one takes advantage of these two properties, adriamycin-DNA induces very high percentages of increase in life span in DBA2 mice inoculated intravenously with L1210 cells and allows a great proportion of mice to survive longer than 30 days. All these data are in favor of a lysosomotropic mode of action of adriamycin-DNA. According to this hypothesis, adriamycin-DNA penetrates only the cells possessing a significant endocytic activity. After degradation of DNA inside the lysosomes, adriamycin becomes free and exerts its toxic activity mostly on those cells, which like some tumor cells, possess besides an high endocytic activity an high mitotic rate. Many normal cells with an high mitotic rate or susceptible to the action of adriamycin but with a low endocytic activity, are in this way protected. © 1974.