The mechanism of enzyme induction by 3', 5'-cyclic nucleotides will be studied in established tissue-culture cell lines derived from rat liver or hepatomas. The induction of tyrosine aminotransferase by derivatives of cyclic AMP will be characterized further in HTC cells. This and other hepatoma cell lines will be examined for additional hepatic enzymes which respond to derivatives of cyclic AMP or cyclic GMP. Cellular components potentially involved in the inductions will be analyzed and compared among the various hepatoma cells and liver. The differences observed will be considered in relation to the differences in cellular responsiveness to cyclic nucleotides. Components being examined include cyclic nucleotide-binding proteins and protein kinases together with proteins which modulate their activities. The function of these proteins in enzyme inductions will be evaluated. BIBLIOGRAPHIC REFERENCES: R. H. Stellwagen and C. W. Mackenzie III. "Differences between Liver and Hepatoma Cells in the Number and Properties of Cyclic AMP Binding Proteins." Adv. Cyclic Nuc. Res. 5, 826 (1975). Presented at Second International Conference on Cyclic AMP, Vancouver, Canada. R. H. Stellwagen and C. W. Mackenzie III. "Identification of a Protein which Selectively Reduces the Apparent Binding Affinity for Cyclic AMP in Hepatoma Cell Extracts." Fed. Proc. 34, 543 (1975). Presented at FASEB meeting, Atlantic City, N. J.