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Antitumor Effects of Polynucleotides and Theophylline¹

Institute of Microbiology, Rutgers University, New Brunswick, New Jersey 08903

Polyadenylic-polyuridylic acid and polyinosinic-polycytidylic acid, as well as theophylline, retard the rate of intradermal growth of Rauscher leukemia virus-induced ascites tumor cells in syngeneic BALB/c mice. The combination of polyadenylic-polyuridylic acid and theophylline tends to affect the growth more than either agent alone, the results being dependent on dosages, timing, and the tumor cell line used. A substantial part of the antitumor activity of these agents, which are also known to modify immune responses, appears to be due to a direct effect on the tumor cells, since the effects of polyadenylic-polyuridylic acid and theophylline were also observed in irradiated mice and usually also after direct treatment of the tumor cells in vitro prior to implantation. In view of data from other cell systems, which show that synthetic polynucleotides stimulate the enzyme responsible for the formation of cyclic adenosine 3',5'-monophosphate and also in view of the fact that theophylline inhibits the enzymes that degrade cyclic adenosine 3',5'-monophosphate, the inhibitory effects noted here are believed to involve alterations in the cyclic adenosine 3',5'-monophosphate system of the tumor cells.

¹ This work was supported by NIH Grants AI 08493 and AI 09343, National Science Foundation Grant GB 20162, and a grant frmm the New York Cancer Research Institute.

² Present address: Section of Hematology and Immunology, Dept. of Medicine, University of California School of Medicine, San Francisco, Calif. 94122.

Received 11/ 5/71. Accepted 5/11/72.

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