Cyclic AMP and adenyl cyclase in brain tumors.

Some of the regulatory mechanisms of cyclic adenosine monophosphate (AMP) production in human brain tumors were investigated by assessing both cyclic AMP levels and adenyl cyclase activity. A large disparity was found between the levels of cyclic AMP of normal brain and brain-tumor tissue. Cyclic AMP levels were much lower in brain tumors (25.8 pmoles (picomoles)/mg protein) than in normal brain (98.8 pmoles/mg protein). These studies also show that the abnormally low levels of cyclic AMP in tumors parallel those of adenyl cyclase. The mean adenyl cyclase activity of brain tissue was found to be 111.0 pmoles of cyclic AMP/min/mg protein, while that of the tumor was only 23.0 pmoles/min/mg protein. Levels of cyclic AMP and adenyl cyclase activity were inversely related to the degree of malignancy. Attempts to stimulate adenyl cyclase in homogenates of human brain and brain tumors resulted in a similar response in both tissues. Norepinephrone was the most effective stimulant and produced a two- to threefold increase in cyclic AMP production, while histamine had no effect. It is concluded that one of the factors governing tumor growth may be a defect in the adenyl cyclase system.