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Changes in Lymphoid Cyclic Adenosine 3':5'-Monophosphate Metabolism during Murine Leukemogenesis¹

Departments of Biochemistry [R. G. K., P-Y. H.] and Microbiology [R. J. D.], the Medical College of Wisconsin, and the Nilwaukee Blood Center, Inc. [R. J. D.], Milwaukee, Wisconsin 53233

Cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels were slightly increased in preleukemic AKR mouse thymus cells, compared with nonleukemic thymus cells, but were markedly reduced in leukemic cells. Adenylate cyclase activity rose during the preleukemic and leukemic phases of leukemogenesis. Although the drop of epinephrine-induced stimulation of thymus adenylate cyclase in the preleukemic phase was probably age related, there was an additional decrease of adenylate cyclase activation by epinephrine in leukemic cells. Cyclic AMP phosphodiesterase activity was slightly higher in preleukemic cells and more than fourfold higher in leukemic thymus, compared with nonleukemic AKR thymus.

These observations suggest that cyclic AMP phosphodiesterase is largely responsible for the low levels of cyclic AMP in leukemic cells. Significant changes in cyclic AMP metabolism are already detectable before neoplastic cells may be found in the thymus.

¹ This investigation was supported by USPHS Grants CA16539, AM11410, and A112507, and by Grant DRG-1224 from the Damon Runyon-Walter Winchell Cancer Fund.

Received 3/31/75. Accepted 5/27/75.