title: Actions of two highly potent organophosphorus neuropathy target esterase inhibitors in mammalian cell lines.
abstract: 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 lines with neural properties (PC-12 and NB41A3) and of nonneural origin (C6 and HeLa). NTE-like esteratic activity is higher in PC-12, HeLa and C6 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 phosphorylated and labeled by [3H-octyl]OBDPO in these cell lines in the same order as their relative NTE esteratic activity. Cytotoxic levels of OBDPO and EOPF (300-500 microM) are generally 10(5) to > 10(7)-fold higher than required for NTE inhibition. PC-12 cells and OBDPO/[3H]OBDPO and EOPF are therefore suitable for research on non-lethal biochemical disruptions from NTE phosphorylation and aging.
authors.affiliation: Department of Environmental Science, Policy and Management, University of California, Berkeley 94720-3112, USA.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: J E
authors.initials: JE
authors.lastname: Casida
mesh_terms: D000818:Animals; D015415:Biomarkers; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002802:Cholinesterases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000633:toxicity*; D006367:HeLa Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D051379:Mice; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology
chemical_list: C092561:2-octyl-4H-1,3,2-benzodioxaphosphorin-2-oxide; D015415:Biomarkers; D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; C100419:ethyl octylphosphonofluoridate; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D002802:Cholinesterases