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8-Chloroadenosine 3',5'-Monophosphate Inhibits the Growth of Chinese Hamster Ovary and Molt-4 Cells through Its Adenosine Metabolite¹

Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032

8-Chloroadenosine 3',5'-monophosphate has been reported to inhibit growth of various mammalian cell lines at micromolar concentrations. We have used Chinese hamster ovary cell lines with mutated cyclic AMP-dependent protein kinase or altered cyclic nucleotide metabolism to show that a metabolite, 8-chloroadenosine, is formed in the medium and is the active inhibitor of cell growth in Chinese hamster ovary cells. Adding adenosine deaminase to the Chinese hamster ovary cell growth media removes the inhibition of cell growth attributed to 8-chloroadenosine 3',5'-monophosphate. Adenosine deaminase or dipyridamole also protects Molt-4 lymphoblasts from the growth-inhibitory effects of 8-chloroadenosine 3',5'-monophosphate.

¹ This work was supported by American Cancer Society Grant BE20 to R. H. K. and M. M. V. L. C. B. J. was supported by a grant from the Fonds der Chemischen Industrie.

² To whom requests for reprints should be addressed, at Department of Anatomy and Cell Biology, Columbia University, P & S Room 12-517, 630 West 168th Street, New York, NY 10032.

³ Institut für Organische Chemie, Fachbereich Biologie-Chemie, Universität Bremen, Leobener Strasse, D-2800 Bremen, Germany.

Received 9/13/90. Accepted 1/ 7/91.

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