ACTIONS OF 2 HIGHLY POTENT ORGANOPHOSPHORUS NEUROPATHY TARGET ESTERASE INHIBITORS IN MAMMALIAN-CELL LINES

Neuropathy target esterase (NTE) is inhibited by many organophosphorus compounds that induce delayed neuropathy, This study examines two of the most potent NTE inhibitors, 2-octyl-4H-1,3,2-benzodioxaphosphorin 2-oxide (OBDPO) and ethyl octylphosphonofluoridate (EOPF), in cell lin es with neural properties (PC-12 and NB41A3) and of nonneural origin ( C-6 and HeLa). NTE-like esteratic activity is higher in PC-12, HeLa an d C-6 cells than in NB41A3 cells and in each case is inhibited 50% by OBDPO and EOPF at 0.03-3.4 nM in vitro and by OBDPO at 0.080-36 nM in situ in culture. An NTE-like protein(s) of about 155 kDa is phosphoryl ated and labeled by [H-3-octyl]OBDPO in these cell lines in the same o rder as their relative NTE esteratic activity. Cytotoxic levels of OBD PO and EOPF (300-500 mu M) are generally 10(5) to > 10(7)-fold higher than required for NTE inhibition. PC-12 cells and OBDPO/[H-3]OBDPO and EOPF are therefore suitable for research on non-lethal biochemical di sruptions from NTE phosphorylation and aging. (C) 1997 Elsevier Scienc e Ireland Ltd.