title: Avian embryonic brain reaggregate culture system. II. NTE activity discriminates between effects of a single neuropathic or nonneuropathic organophosphorus compound exposure.
abstract: Biochemical responses after a single exposure to either a neuropathic or a nonneuropathic organophosphorus compound (OP) were compared using chick embryonic brain cell reaggregates. Ten-day-old chick embryo brains were dissociated and then reaggregated and maintained in a chemically defined, serum-free medium without antibiotics. Seven days later, these cultures were treated for 20 min with either neuropathic diisopropyl phosphorofluoridate (DFP, 10(-4) M) or nonneuropathic paraoxon (10(-6) M). Reaggregates were assayed for acetylcholinesterase (ACHE), neuropathy target esterase (NTE), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) activities for up to 32 days after exposure. These enzymes were examined due to inhibition of activity as a result of acute OP toxicity (ACHE) or delayed toxicity (NTE, CNP). DFP inhibited > 95% of NTE activity immediately after exposure. By Postexposure Day 2, NTE specific activity was 22% of untreated activity but was similar to the untreated group levels by Postexposure Day 7. Paraoxon exposure did not affect NTE activity. Both paraoxon and DFP inhibited > 99% of ACHE activity immediately after exposure. By Postexposure Day 2, ACHE specific activity in paraoxon-exposed cultures had recovered while ACHE remained 56% inhibited in DFP-exposed cultures. Both paraoxon- and DFP-exposed cultures recovered ACHE activity immediately following OP exposure if treated postexposure with an oxime reactivator, 2-pralidoxime. CNP specific activity was not affected by either paraoxon or DFP. These results demonstrated distinct differences in reaggregate NTE and ACHE activities after single exposure to neuropathic DFP and nonneuropathic paraoxon similar to those in avian in vivo assays.
authors.affiliation: Department of Pathology, School of Veterinary Medicine, University of California at Davis 95616.
authors.forename: K A
authors.initials: KA
authors.lastname: Funk
authors.forename: C H
authors.initials: CH
authors.lastname: Liu
authors.forename: R J
authors.initials: RJ
authors.lastname: Higgins
authors.forename: B W
authors.initials: BW
authors.lastname: Wilson
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D002265:Carboxylic Ester Hydrolases / Q000032:analysis / Q000187:drug effects; D002449:Cell Aggregation; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D002642:Chick Embryo; D046508:Culture Techniques; D007531:Isoflurophate / Q000494:pharmacology; D009249:NADP / Q000032:analysis / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010261:Paraoxon / Q000494:pharmacology
chemical_list: D009943:Organophosphorus Compounds; D007531:Isoflurophate; D009249:NADP; C013462:2',3'-cyclic NADP; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D000110:Acetylcholinesterase; D010261:Paraoxon