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Prolonged Induction of Hepatic Ornithine Decarboxylase and Its Relation to Cyclic Adenosine 3':5'-Monophosphate-dependent Protein Kinase Activation after a Single Administration of Diethylnitrosamine¹

Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, Arizona 85724

After a single injection of diethylnitrosamine (200 mg/kg), there was a rapid increase in the activity ratio of hepatic cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase (within 1 hr) followed by the induction of ornithine decarboxylase which was detectable by 3 hr. Both the cyclic AMP-dependent protein kinase activity ratio and the activity of ornithine decarboxylase were significantly elevated above controls for 7 days following the administration of diethylnitrosamine. A single noncarcinogenic dose of diethylnitrosamine (25 mg/kg) did not increase the cyclic AMP-dependent protein kinase activity ratio or induce ornithine decarboxylase activity at 24 hr postadministration. However, serial administration of diethylnitrosamine (25 mg/kg) for 4 or 7 days resulted in an increased activity ratio of cyclic AMP-dependent protein kinase and increased ornithine decarboxylase activity. This is the first report of a prolonged increase in both the activity ratio of hepatic cyclic AMP-dependent protein kinase and the activity of ornithine decarboxylase in response to a single carcinogenic dose of diethylnitrosamine.

¹ This work was supported by USPHS Research Grant CA-14783 from the National Cancer Institute.

² Recipient of Fellowship CA-06132 from the National Cancer Institute. To whom requests for reprints should be addressed, at Department of Pharmacology, College of Medicine, Health Sciences Center, The University of Arizona, Tucson, Ariz. 85724.

³ Recipient of Research Career Development Award CA-00072 from the National Cancer Institute.

Received 11/10/78. Accepted 5/ 8/79.