Reduction of acute adriamycin toxicity in mice treated with adenosine.
The effects of adenosine on the acute toxicity and oncolytic activity of adriamycin (ADR) were evaluated in mice. When administered as a single i.p. injection of 17.5 mg/kg, adriamycin produced death in all mice within 12 days after treatment, with a mean survival time of 5-9 days. In contrast, the mean survival time of mice administered adenosine subcutaneously (200 mg/kg) in addition to adriamycin was significantly increased compared to adriamycin-treated mice. The protection elicited by adenosine was apparently not a generalized phenomenon of purines, however, since neither hypoxanthine nor inosine were effective protectants. Although a number of adenosine treatment schedules were tested, it was found that adenosine given immediately after adriamycin was as effective as multiple adenosine injections. Administration of adenosine had no apparent effect on adriamycin-mediated changes in ventricular weight, leukocyte count, elevated serum lactic dehydrogenase (LDH) activity or in the histopathologic changes observed in selected tissues. Two grossly observable effects of adenosine administration were lethargy and peripheral hypothermia, which were first noticed approximately 15 min after adenosine administration and which lasted for up to 2 hr. Finally, adenosine had no adverse effect on the antitumor efficacy of adriamycin against L1210 ascites cells inoculated i.p. to BDF1 mice.