Differences were found between the toxicologic effects of tubercidin and those of 7-deazainosine which were consistent with the idea that 7-deazainosine requires conversion into anabolites of tubercidin in order to exert biologic effects. In rodents treated parenterally, and in dogs treated orally, tubercidin was 6- to 20-fold more toxic than 7-deazainosine. Severe local reactions occurred only in rats treated with tubercidin. In contrast, necrosis of the walls of the intrahepatic bile ducts and of the myocardium was found only in rats treated with 7-deazainosine. Pulmonary edema, focal necrosis of hepatic parenchyma, and generalized lymphoid depression were observed after either drug. After treatment of dogs with tubercidin, pneumonia, renal tubular necrosis, and gastrointestinal toxicity were severe, whereas hepatotoxicity was slight and infrequent. In contrast, after treatment with 7-deazainosine, hepatotoxicity was severe, whereas the other toxic effects were insignificant. Only tubercidin caused atrophy of the Islands of Langerhans.

In view of the lack of local and renal toxicity, 7-deazainosine may offer therapeutic advantages over tubercidin provided that hepatotoxicity is not a limiting factor.

1

This investigation was supported in part by a research grant (CA 04130) from the National Cancer Institute, USPHS.

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©1969 American Association for Cancer Research.
1969
Cancer Research, Inc.