Inhibition of extension outgrowth in differentiating rat C6 glioma cells by chlorpyrifos and chlorpyrifos oxon: effects on microtubule proteins.

The aim of this work was to assess the toxic effects of the phosphorothionate insecticide chlorpyrifos (CPF) and its major in vivo metabolite chlorpyrifos oxon (CPO) on differentiating rat C6 glioma cells. At sublethal concentrations (1-10 microM), both compounds were able to inhibit the development of extensions from C6 cells induced to differentiate by sodium butyrate. Western blot analysis of C6 cell lysates revealed that 4 h exposure to CPF was associated with decreased levels of the cytoskeletal protein MAP1B compared to controls, whereas the levels of the cytoskeletal proteins tubulin and MAP2c were not significantly affected. Western blot analysis of extracts of cells treated with CPO showed a significant, concentration-dependent decrease in the levels of tubulin after 24 h. MAP-1B levels were also significantly decreased. The above changes were not temporally related to acetylcholinesterase (AChE) inhibition. These results suggest that both CPF and CPO can exert toxic effects directly on glial cell differentiation and that the latter compound has a potent effect on the microtubule network.