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Activation of Guanylate Cyclase by Streptozotocin and 1-Methyl-1-nitrosourea¹

Division of Endocrinology and Metabolism, Department of Medicine, University of Miami School of Medicine, Miami, Florida 33152

Streptozotocin has been shown to induce the production of a variety of tumors in rats. The present report demonstrates that streptozotocin and 1-methyl-1-nitrosourea, a component of the streptozotocin molecule and a known carcinogen, stimulate the enzyme guanylate cyclase which catalyzes the production of guanosine 3',5'-monophosphate. At a maximal concentration of 3 mg/ml, these agents activated guanylate cyclase approximately 30-fold in liver, 20-fold in kidney, 15-fold in cerebellum, 15- to 30-fold in cerebrum, 4- to 20-fold in heart, 12-fold in brain stem, 10-fold in lung, and 2-fold in pancreas.

Since recent evidence suggests a role for guanosine 3',5'-monophosphate in malignant transformation, the data may help explain the tumor-inducing capacity of these agents.

¹ This work supported by NIH Grant HL 13715-05, 06 and NIH Training Grant 5-T01 AM05710-04.

² Investigator of the Howard Hughes Medical Institute.

Received 7/28/76. Accepted 9/27/76.

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