The retinoids, a group of natural and synthetic analogues of Vitamin A, have been shown to possess anticarcinogenic properties in vivo. We have recently demonstrated that natural retinoids will completely eliminate the expression of carcinogen induced morphological transformation in cultured C3H/10T1/2CL8 cells. This proposal seeks to obtain a better understanding of the mechanism whereby retinoids can inhibit transformation. This proposal is divided into 2 sections. In section 1 the effects of retinoids on transformation will be examined in detail, attempts will be made to isolate initiated cells, the relationship between tumor promoters and retinoids will be investigated, and the effects of the retinoid content of feral serum studied. In section 2, it is planned to investigate the biochemical aspects of retinoid activity. Using parental C3H/10T1/2 cells, initiated cells and transformed cells, we proposed to study the effects of retinoids on a. the biosynthesis of membrane glycolipids and glycoproteins using labeled membrane precursors, and b. the behavior of cell membranes using the fluorescence recovery after photobleaching technique to measure membrane mobility, and by a modification of the technique membrane fluidity. Finally, we propose to measure the levels of retinoic acid binding protein and of retinol binding protein in the cytosol of parental, initiated and transformed cell lines.
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