Avian embryonic brain reaggregate culture system: II. NTE activity discriminates between effects of a single neuropathic or nonneuropathic organophosphorus compound exposure

Kathleen A. Funk, Chen Hsuan Liu, Robert Higgins, Barry W. Wilson

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)159-163
Number of pages5
JournalToxicology and Applied Pharmacology
Volume124
Issue number1
DOIs
StatePublished - Jan 1 1994

Fingerprint

Organophosphorus Compounds
Paraoxon
Isoflurophate
Acetylcholinesterase
Brain
Cyclic Nucleotides
Phosphoric Diester Hydrolases
Carboxylesterase
Toxicity
Oximes
Serum-Free Culture Media
Chick Embryo
neurotoxic esterase
Assays
Anti-Bacterial Agents
Enzymes

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Avian embryonic brain reaggregate culture system : II. NTE activity discriminates between effects of a single neuropathic or nonneuropathic organophosphorus compound exposure. / Funk, Kathleen A.; Liu, Chen Hsuan; Higgins, Robert; Wilson, Barry W.

In: Toxicology and Applied Pharmacology, Vol. 124, No. 1, 01.01.1994, p. 159-163.

Research output: Contribution to journalArticle

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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.",
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