Studies on the Molecular Pathogenesis of Organophosphorus Compound- Induced Delayed Neurotoxicity (OPIDN).
Insecticide Action 1989:205-216
The delayed neurotoxicity effect arising from exposure to tri-o- cresyl-phosphate (78308) (TOCP) in humans and sensitive animal species was discussed. Neurologic dysfunctions became evident as ataxia and bilateral paralysis after a delay period of 6 to 14 days. Earlier evidence of damage included the formation of aggregates of neurotubules and neurofilaments which later condensed. Increased activity of calcium ion calmodulin-kinase-II (CaM-kinase-II) resulted from TOCP exposure at neurotoxic dose levels. This was followed by enhanced CaM-kinase-II dependent autophosphorylation, as well as phosphorylation of cytoskeletal proteins. Phosphorylation of MAP-2 reduced its interaction with tubulin and diminished its ability to promote tubulin assembly into microtubules. The axonal transport was disrupted by aggregation and accumulation of these structures, resulting in the accumulation of mitochondria and/or endoplasmic reticulum in the distal parts of the axons with subsequent release of calcium into the axoplasm. In turn, this caused axonal membrane mechanisms to be disrupted, causing focal internodal swelling and degeneration which spread to involve the entire distal axon.
NIOSH-Grant; Neurotoxic-effects; Nervous-system-disorders; Neuropathology; Organo-phosphorus-compounds; Plasticizers;
Pharmacology Duke University Medical Center Box 3813 Durham, NC 27710
Book or book chapter;
Neurotoxic Disorders; Neurotoxic-effects;
Duke University, Durham, North Carolina