Effects of Retinoid -Glucuronides and N-Retinoyl Amines on the Differentiation of HL-60 Cells in Vitro

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Abstract
Retinoyl .beta.-glucuronide and retinyl .beta.-glucuronide, which are naturally occurring water-soluble metabolites of vitamin A, induce the granulocytic differentiation of HL-60 cells in vitro, as evidenced by an increased reduction of nitroblue tetrazolium. The relative effectiveness of various retinoids in differentiation is retinoic acid > retinoyl .beta.-glucuronide > retinyl .beta.-glucuronide. Under the selected assay conditions, retinol, hydroxyphenyl-retinamide, retinamide, and N-retinoyl-phenylalanine are essentially inactive in differentiation. At concentrations of retinoids from 10-9 to 10-5 M, cell viability was best with the retinoid .beta.-glucuronides and retinamide, less than retinoic acid and retinol, and poorest with the N-retinoyl aromatic amines. Cellular growth was depressed only slightly by retinyl .beta.-glucuronide and retinamide, but to a greater degree by the other derivatives. Retinoyl .beta.-glucuronide was hydrolyzed in part to retinoic acid, whereas retinyl .beta.-glucuronide was cleaved to retinol, if at all, at a very slow rate. Under the selected assay conditions, retinoic acid and the retinoid .beta.-glucuronides primarily induce the differentiation of HL-60 cells, whereas the N-retinoyl aromatic amines show cytotoxicity.

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