Diazinon oxon affects the differentiation of mouse N2a neuroblastoma cells.
The aim of this study was to assess the neurotoxicity of diazinon oxon (DZO), a major in vivo metabolite of the phosphorothionate insecticide diazinon (DZ), on differentiating mouse N2a neuroblastoma cells. When used at concentrations of 1, 5 and 10 microM, DZO did not cause cell death but it impaired the outgrowth of axon-like processes after 24 h. Densitometric scanning of Western blots of lysates of N2a cells revealed that exposure to 5 or 10 microM DZO for 24 h increased the expression of phosphorylated neurofilament heavy chain (NFH) compared to controls, while there was no significant change in total NFH. By contrast, treatment of N2a cells with 1-10 microM DZO resulted in marked reductions in the expression of the axon growth-associated protein GAP-43. DZO-treated cells also showed an increased expression of the heat shock protein HSP-70 compared to controls. The above biochemical changes were not temporally related to inhibition of acetylcholinesterase (AChE). These data suggest that biologically relevant, subcytotoxic levels of DZO may exert neurotoxic effects on differentiating cells and that the mechanisms involved are different from those attributed to its parent compound.
Sidiropoulou
Erasmia
E
Department of Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool, Leahurst CH647TE, UK.
Sachana
Magdalini
M
Flaskos
John
J
Harris
Wayne
W
Hargreaves
Alan J
AJ
Woldehiwet
Zerai
Z
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003976:Diazinon / Q000031:analogs & derivatives* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D019922:GAP-43 Protein / Q000187:drug effects / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D051379:Mice; D016501:Neurites / Q000187:drug effects*; D009447:Neuroblastoma; D016900:Neurofilament Proteins / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D019922:GAP-43 Protein; D018840:HSP70 Heat-Shock Proteins; D007306:Insecticides; D016900:Neurofilament Proteins; C051774:neurofilament protein H; D003976:Diazinon