Comparative toxicity of adriamycin and adriamycin-DNA in rats

Adriamycin (ADR) can be linked to DNA without loss of its antitumoral activity while reducing the acute toxicity of free ADR (Deprez--DeCampeneere et al., 1979, 1980). However, the potential chronic toxic effects of both forms of ADR are poorly documented. For such a study, it is necessary to establish the sequence of treatment allowing the administration of a sufficient amount of drugs to induce chronic toxicity and a schedule leading to prolonged survival of animals. In this study, 24 Lewis rats were injected twice a week during four weeks with either free or DNA-linked ADR, and three dose levels were tested: 4, 2 and 1 mg/kg. Our results indicated that the total cumulative dose of ADR should not exceed 8 mg/kg over one month, if prolonged survival is desired. The binding of ADR to DNA seemed also to reduce the acute toxic effects induced by free ADR, in rats. However, such a beneficial effect was not observed when the chronic nephrotoxicity was considered since characteristic renal lesions were observed in all long-term survivors, whatever the dose and the form of ADR received.