HYDROXYL RADICALS AS AN EARLY SIGNAL INVOLVED IN PHORBOL ESTER-INDUCED MONOCYTIC DIFFERENTIATION OF HL-60 CELLS

A useful model for the study of monocytic differentiation has been the induction of myeloid leukemic cell differentiation. Employing human H L60 leukemic cells, we sought to clarify whether reactive oxygen inter mediates (ROI) are involved in phorbol myristate acetate (PMA)-induced monocytic differentiation. We found that hydroxyl radical (OH) scaven ger pyrrolinodimethylthiocarbamate (PDTC), but not O-2(-), H2O2 or O-1 (2) sc avenger, suppressed PMA-mediated HL60 cell differentiation in a dose dependent fashion (0.1 to 1.0 mu M). PDTC suppressed OH but not O-2(-) or H2O2 production by HL60 cells stimulated with PMA (32 nM). A ddition of PDTC before and right after, but not 16 hours after, PMA st imulation inhibited PMA-induced HL60 cell differentiation. Taken toget her, these findings indicate that OH, but not O-2(-), H2O2, or O-1(2), is a critical early signal involved in the PMA-induced monocytic diff erentiation of HL60 cells. (C) 1994 Academic Press, Inc.