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Toxicological and Antiproliferative Effects of N⁶-(²-Isopentenyl)adenosine, a Natural Component of Mammalian Transfer RNA¹

Department of Experimental Therapeutics, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York 14203

N⁶-(²-Isopentenyl)adenosine inhibited the growth of Ehrlich carcinoma ascites and leukemia L1210 but not that of Sarcoma 180, adenocarcinoma 755, and Walker 256 carcinosarcoma. Pancreatic atrophy, lymphoid depression, superficial gastric ulcers, and reduction of mitoses in intestinal crypts were seen in rats treated with the compound. In rats and dogs, the drug caused hepatotoxicity and granulocytosis. In rats, the granulocytosis was related to a release of mature granulocytes from the bone marrow without alteration of differentiation and proliferation rates of hematopoietic cells. Regeneration of liver after partial hepatectomy was also inhibited by the drug in rats. Hypotension was measured in dogs after single i.v. doses of the drug. Several of these effects were comparable to those caused by adenosine or some of its analogs.

¹ This investigation was supported in part by USPHS Grants CA-04130 and CA-11047.

Received 8/15/69. Accepted 1/16/70.