Maintenance of epithelial differentiation is one of the biological functions of vitamin A and explains current interest in this nutrient as a chemopreventative agent of epithelial cancer. Therefore, current research efforts center on the elucidation of possible sites and mechanisms of action of the vitamin. These were pursued at the following levels: 1) Protein glycosylations: The key intermediates in the pathway of mannose incorporation into glycoproteins were studied to identify vitamin A dependent steps. An accumulation of mannose phosphate and a concomitant decrease in GDP-mannose formation were found in liver in vivo and cultured tracheas from vitamin A-deficient hamsters. Since the activity of the enzyme responsible for GDP-mannose synthesis from GTP and mannose phosphate was not affected, lowered GTP pools may be responsible for the effect of vitamin A deficiency on mannose incorporation. 2) Retinol transport: The possibility that transport of retinol to mouse epidermal cells is mediated via a cell surface receptor for the plasma retinol binding protein was tested, utilizing (3H)retinol-labeled RBP and cultured mouse epidermal cells. The uptake of (3H)retinol was inhibited by holo-RBP with an apparent Km of 2-4 MuM, the concentration at which RBP is found in the serum. (3H)Retinol uptake from RBP was not influenced by inhibitors of receptor mediated endocytosis and using 125I-labeled RBP no evidence of direct binding or internalization of RBP was found. These data are consistent with retinol being delivered from RBP to epidermal cells via a transitory interaction with a cell surface receptor. 3) Effect of dietary cycles of vitamin A deficiency and retinoic acid repletions on incisor tooth of the rat. The majority of rats (60-70%) maintained for more than 11 cycles on alternating dietary regimens of vitamin A-deficient (10 days) and retinoic acid-supplemented (18 days) diets developed incisor """"""""tooth masses."""""""" These masses appeared to originate from ectopic epithelial and mesenchymal cells which had crossed the dentin wall and responded to intermittent availability of retinoic acid in the diet.
