ASCORBATE INCREASES THE 1,25-DIHYDROXYVITAMIN-D-3-INDUCED MONOCYTIC DIFFERENTIATION OF HL-60 CELLS

1,25 Dihydroxyvitamin D-3 (calcitriol) induces differentiation of HL-6 0 leukemia cells. We studied the in vitro effect of a physiological co ncentration of ascorbate as potentiator of 1,25 dihydroxyvitamin D-3 [ (OH)(2)D-3] activity by determining different markers of differentiati on: nitroblue tetrazolium reduction, nonspecific esterase activity, an d the expression of CD11b and CD14 surface antigens. Nitroblue tetrazo lium reduction and nonspecific esterase activity increased up to 50% i n the presence of both 1,25 (OH)(2)D-3 plus 0.2 mM ascorbate (ASC), co mpared with (OH)(2)D-3 as a unique agent. ASC also increased the expre ssion of specific surface antigens (CD11b and CD14) during differentia tion induced by 1,25 (OH)(2)D-3, the effect being more pronounced afte r 48 hours of treatment with 10(-8) M 1,25 (OH)(2)D-3. Furthermore, 1, 25 (OH)(2)D-3 alone increased intracellular cAMP level during differen tiation, and the addition of ASC increased its concentration from 60 t o 100% above the level reached with 1,25 (OH)(2)D-3 as unique agent. A SC did not enhance the antiproliferative effect of calcitriol, suggest ing that it only affects the ability of 1,25 (OH)(2)D-3 to promote dif ferentiation of HL-60 cells.