UNCOUPLING OF INCORPORATION OF ASCORBIC-ACID AND APOPTOSIS INDUCTION

Exposure of human promyelocytic leukemic HL-60 cells to millimolar con centration of sodium ascorbate induced apoptotic cell death. The exten t of apoptosis induction was a positive function of temperature at the time of exposure. The incorporation of [1-C-14] ascorbic acid into th e cytosolic fraction of HL-60 cells was also temperature-dependent, an d competitively inhibited by active analogs (L-ascorbic acid, sodium L -ascorbate, D-isoascorbic acid, sodium 6-beta-O-galactosyl-L-ascorbate , sodium 5,6-benzylidene-L-ascorbate), but not by inactive analogs (L- ascorbic acid-2-phosphate magnesium, L-ascorbic acid 2-sulfate). Calci um depletion, which had considerably reduced the apoptosis-inducing ac tivity of sodium ascorbate, did not affect the intracellular incorpora tion of [C-14] ascorbic acid These data suggests that cell death might not be simply induced by the intracellular incorporation of ascorbate , but rather initiated by the rapid elevation of intracellular Ca2+ co ncentration, possibly mediated by an as yet unidentified temperature-s ensitive mechanism.