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Relationship of tri-O-cresyl phosphate-induced delayed neurotoxicity to enhancement of in vitro phosphorylation of hen brain and spinal cord proteins.

Authors
Patton-SE; Lapadula-DM; Abou-Donia-MB
Source
J Pharmacol Exp Ther 1986 Nov; 239(2):597-605
NIOSHTIC No.
00165177
Abstract
The relationship of tri-O-cresyl-phosphate (78308) (TOCP) induced delayed neurotoxicity to the enhancement of in-vitro brain and spinal cord protein phosphorylation was studied in hens and rats, to investigate organophosphorus compound induced delayed neurotoxicity (OPIDN). Adult leghorn-hens were treated with single oral doses of 750mg/kg TOCP, 837mg/kg of leptophos (21609905), 750mg/kg tri-p- cresyl-phosphate (78320) (TPCP), or 5mg/kg parathion (56382). Male Sprague-Dawley-rats received 750mg/kg TOCP by gavage for study of species effects. After 21 days, in-vitro protein phosphorylation was determined in subcellular fractions from hen brains and spinal cords. The TOCP dose was correlated with neurologic deficit and calcium ion dependence of phosphorylation. The non OPIDN producing organophosphorus compounds TPCP and parathion had no effect on phosphorylation or clinical condition. Hens given leptophos developed more severe delayed neurological deficit, earlier than those given TOCP; phosphorylation was increased significantly. Young chicks and adult rats given the same treatment as the hens did not show signs of OPIDN or significant change in phosphorylation. Results suggest the involvement of calcium dependent brain protein phosphorylation in the etiology of OPIDN.
Keywords
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Laboratory-animals; Toxicology; Phosphorus-compounds; In-vitro-studies; Cholinesterase-inhibitors; Neurotoxicology; Protein-chemistry
Contact
Pharmacology Duke University Medical Center Box 3813 Durham, NC 27710
CODEN
JPETAB
CAS No.
78-30-8; 21609-90-5; 78-32-0; 56-38-2
Publication Date
19861101
Document Type
Journal Article
Funding Amount
665055.00
Funding Type
Grant
Fiscal Year
1987
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-02003
Issue of Publication
2
Priority Area
Neurotoxic-effects
Source Name
Journal of Pharmacology and Experimental Therapeutics
State
NC
Performing Organization
Duke University, Durham, North Carolina
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