title: The effects of acute pesticide exposure on neuroblastoma cells chronically exposed to diazinon.
abstract: Speculation about potential neurotoxicity due to chronic exposure to low doses of organophosphate (OP) pesticides is not yet supported by experimental evidence. The objective of this work was to use a cell culture model of chronic OP exposure to determine if such exposure can alter the sensitivity of nerve cells to subsequent acute exposure to OPs or other compounds. NB2a neuroblastoma cells were grown in the presence of 25 microM diazinon for 8 weeks. The OP was then withdrawn and the cells were induced to differentiate in the presence of various other pesticides or herbicides, including OPs and OP-containing formulations. The resulting outgrowth of neurite-like structures was measured by light microscopy and quantitative image analysis and the IC(50) for each OP or formulation was calculated. The IC(50) values in diazinon-pre-exposed cells were compared with the equivalent values in cells not pre-exposed to diazinon. The IC(50) for inhibition of neurite outgrowth by acute application of diazinon, pyrethrum, glyphosate or a commercial formulation of glyphosate was decreased by between 20 and 90% after pre-treatment with diazinon. In contrast, the IC(50) for pirimiphos methyl was unaffected and those for phosmet or chlorpyrifos were increased by between 1.5- and 3-fold. Treatment of cells with chlorpyrifos or with a second glyphosate-containing formulation led to the formation of abnormal neurite-like structures in diazinon-pre-exposed cells. The data support the view that chronic exposure to an OP may reduce the threshold for toxicity of some, but by no means all, environmental agents.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Liverpool L69 3GE, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Axelrad
authors.forename: C V
authors.initials: CV
authors.lastname: Howard
authors.forename: W G
authors.initials: WG
authors.lastname: McLean
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D003976:Diazinon / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D007091:Image Processing, Computer-Assisted; D007306:Insecticides / Q000494:pharmacology*; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009447:Neuroblastoma / Q000473:pathology; D010575:Pesticides / Q000633:toxicity*
chemical_list: D004338:Drug Combinations; D007306:Insecticides; D010575:Pesticides; D003976:Diazinon