Activation of guanylate cyclase by streptozotocin and 1-methyl-1-nitrosourea.
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 inheart, 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.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005947:Glucose / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D051381:Rats; D013311:Streptozocin / Q000494:pharmacology*; D014508:Urea / Q000494:pharmacology
D009607:Nitrosourea Compounds; D013311:Streptozocin; D008770:Methylnitrosourea; D014508:Urea; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D005947:Glucose