Animals will be irradiated throughout the coming year to maintain a pool of intestinal tumor-bearing rats. During this period, we will also continue to induce intestinal tumors in other rats with DMH in order to have animals for comparison. Our preliminary in vitro investigations of the effect of the cyclic nucleotides and prostaglandin upon the growth of the human colon cells will be studied more extensively. Correlations of nucleotide levels with the in vitro synthesis of carcinoembryonic antigen by these cells were recently initiated and will be completed this final year. During this past year, we reported that hydrolytic activity was elevated in intestinal tumors, thus possibly accounting for the lower cAMP levels. This coming year, we intend to determine the adenylate cyclase activities in the malignancies thus finding whether there is a defect in the synthetic activities of cAMP as well. These results will then be related to similar investigations of the chemically induced tumors where possible. Assays for the prostaglandins in these tissues will also be initiated. The significance of our preliminary findings of lower intracellular cAMP concentrations in the tumor-sensitized lymphoid cells will be investigated in greater detail. Correlations will be made with the levels of the cyclic nucleotides and the degree of cytotoxicity. We will attempt to determine if there is any relationship of the prostaglandin concentrations in the sensitized lymphoid cells to the degree of killing measured by the cytotoxicity assay.