Micronuclei Induction and Neurotoxic Effect in C6 Glioma Cells Exposed to Low Concentrations of Diazinon, an Organophosphorus Compound

Abstract

Background: The presence of doses of diazinon far lower than IC50 cholinesterase activity was reported in plasma of pregnant women and newborns living in agricultural areas. Objective: In the current study, we investigated the possibility of neurotoxicity induction by exposing cultured gliotypic C6 cells to a similar range of concentrations, for 24 h, at 37°C. Materials and methods: Confluent C6 cellswere exposed to diazinon (DZN) at concentrations from 200ng/L to 0.002ng/L. The maintenance of confluence, the induction of micronuclei and the expression of molecules related to the cholinergic system were verified, by morphological, biochemical and immunohistochemical methods, in order to check the effects of the altered modulation of the cholinergic signal on glial-like cells. Results: The exposure to 0.002ng/L showed significant effecton micronuclei occurrence since the exposure to 0.002ng/L, while the inhibition on butyrylcholinesterase activity showed significant variations starting from the exposure to 0.2ng/L up to 200ng/L. Acetylcholinesterase activity was significantly inhibited only by the exposure to 200ng/L. The immunohistochemical localization of choline acetyltransferase and fibronectin showed dramatic variation only in C6 cells exposed to 200ng/L. Conclusion: The low doses of DZN investigated affect the investigated features of glial-like cells, mainly starting from the 0.2ng/L dose, while the effects on AChE activity and ChAT and fibronectin-immuorectivity were clearly exerted in cell cultures exposed to 200ng/L. Collectively, these findings translated to the in vivo functions of glial cells indicate that exposure to doses that are nontoxic to adult organisms may weaken the brain defense and functions of glial cells through an AChE-mediated mechanisms.