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Elevated Plasma and Urinary Guanosine 3':5'-Monophosphate and Increased Production Rate in Patients with Neoplastic Diseases¹

Departments of Medicine [R. K. C., S. M. S., D. H. L., T. G. M., M. S., D. W. N., A. R., D. R.] and Biometry [F. S.], Emory University School of Medicine, Atlanta, Georgia 30322

The plasma and 24-hr urinary levels of cyclic adenosine 3':5'-monophosphate and of cyclic guanosine 3':5'-monophosphate (cGMP) were determined for 19 healthy normal patients, 54 patients with six types of nonneoplastic diseases (cholelithiasis, peptic ulcer, coronary heart disease, hypertension, regional ileitis, and cirrhosis), and 54 patients with five types of neoplastic disease (cancers of the lung, colon, and breast, acute myelocytic leukemia, and Hodgkin's disease). The cyclic adenosine 3':5'-monophosphate levels of urine and plasma in normal subjects, in noncancer subjects, and in cancer subjects did not differ significantly. The cGMP levels in the noncancer group were similarly unchanged from those in the normal group. However, mean cGMP levels in the urine and plasma of patients with neoplastic diseases were, respectively, 2- and 3-fold greater than the normal values (p < 0.005 for urine and p < 0.05 for plasma). Pharmacokinetic studies with [³H]cGMP in nine healthy controls and 15 patients with neoplasia showed that the mean production rate of this nucleotide in patients with metastatic cancer was elevated when compared to normal patients, but many values fell within the normal range. In acute leukemia, the production rate was seven times normal, with four of five patients having values clearly outside the normal range. The plasma clearance rate in patients with neoplasia was not decreased when compared to that in normal patients. It is proposed that an increased production rate, rather than any change in plasma clearance, accounts for the increased levels of cGMP in the plasma and urine of some patients with neoplastic disease.

¹ Supported by USPHS Grants CA12646 and RR00039.

² To whom requests for reprints should be addressed, at Emory University, P. O. Box 23410, Atlanta, Ga. 30322.

Received 11/ 9/79. Accepted 7/21/80.