Diacylglycerols (DAGs) are found in the colon lumen from dietary sources, desquamated epithelial cells, and lyzed bacteria. They may serve as promoting agents for this cell type. A series of saturated and unsaturated DAGs will be assayed for biological activity parallel to that already known to be induced by TPA on 5 classes of human colonic epithelial cells in primary culture. These classes are different stages in the development of colon carcinomas. Specifically we will measure plasminogen-activator release from carcinomas; plasminogen-activator release from advanced stage premalignant cells from villous adenomas (benign tumors); the destruction aznd invasion of adenoma colonies by cocultivated carcinoma cells; the proliferative fraction of early stage premalignant cells from tubular adenomas; the proliferative fraction in cultures of very early stage preneoplastic cells from familial polyposis patients; the proliferative fraction and the steady-state levels of keratin polypeptides in normal cells. The ability of the biologically active DAGs to inhibit the binding of 3H-phorbol dibutyrate to colon carcinoma cells will be determined. Inhibition of the promoting effects of DAGs by the calcium soaps of monocarboxylic and dicarboxylic fatty acids, also found in the gut, will be measured. The effect of pretreatment of colonic epithelial cells with retinoids on DAG stimulated promotion will be assayed.
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