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Cyclic 3',5'-Nucleotide Monophosphate Phosphodiesterase Activity in Hepatomas of Different Growth Rates¹

Departments of Biochemistry [A. R. R., H. P. M.] and Pharmacology [W. L. W.], Howard University College of Medicine, Washington, D. C. 20001

Cyclic 3',5'-nucleotide monophosphate phosphodiesterase activity was determined for seven hepatomas of different growth rates and host livers. Activity was measured in the soluble fraction of the cell (78,000 x g) in the presence and absence of 40 mM imidazole.

Phosphodiesterase activity in all hepatomas studied was decreased to levels of 60% or less of control livers of non-tumor-bearing rats. Corresponding decreases in the imidazole-stimulated phosphodiesterase activity were observed for hepatomas. Conversely, phosphodiesterase activity of 24-hr regenerating liver was elevated slightly above those for sham-operated controls. Reduced phosphodiesterase activity was observed only in host livers of animals bearing hepatomas 7800 and 7777.

In the presence of imidazole, phosphodiesterase activity in all tissues was stimulated 110 to 135% of basal levels. Differences in the pH-activity profiles were observed between phosphodiesterase from normal and neoplastic liver. Phosphodiesterase of normal liver had a well-defined pH optimum at 7.4, whereas the activity from hepatoma had a broader optimum ranging from 6.2 to 7.4.

Kinetic plots of the hydrolysis of cyclic adenosine 3',5'-monophosphate exhibited anomolous behavior suggesting that both normal and neoplastic tissue contain at least two different phosphodiesterase activities. Apparent Michaelis constants for the high- and low-affinity enzymes ranged from 2.5 to 7.6 µM and from 39 to 54 µM, respectively.

¹ This work was supported in part by USPHS Grants CA-11491-03 and CA-10729.

Received 6/13/72. Accepted 8/25/72.