Department of Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool, Leahurst, CH64 7TE, UK.
Toxicol In Vitro. 2009 Dec;23(8):1548-52. doi: 10.1016/j.tiv.2009.07.005. Epub 2009 Jul 10.
The purpose of this study was to evaluate the toxicity of diazinon oxon (DZO), a major in vivo metabolite of the organophosphate insecticide diazinon (DZ), on differentiating rat C6 glioma cells. At concentrations shown to be non-cytotoxic by both the MTT and the Kenacid blue dye binding assays (1, 5 and 10 microM), DZO caused after 24h a reduction in the number of extensions developed from C6 cells induced to differentiate by serum withdrawal and addition of sodium butyrate. Densitometric scanning of Western blots of extracts of C6 cells demonstrated that, at all concentrations used, DZO decreased after 24h the expression of glial fibrillary acidic protein (GFAP) compared to controls. In addition, exposure to 10 microM DZO for 24h reduced the levels of tubulin and microtubule associated protein 1B (MAP1B). On the other hand, levels of MAP2c were not affected by DZO treatment. In contrast to our previous data on DZ, the above findings suggest that its oxon metabolite, DZO, may, at biologically relevant, subcytotoxic concentrations, interfere with glial cell differentiation.
本研究旨在评估有机磷杀虫剂敌敌畏（DZ）的主要体内代谢物敌敌畏氧（DZO）对分化大鼠 C6 神经胶质瘤细胞的毒性。在 MTT 和肯酸蓝染料结合测定（1、5 和 10μM）显示非细胞毒性的浓度下，DZO 在 24 小时后导致由血清撤离和添加丁酸钠诱导分化的 C6 细胞产生的突起数量减少。C6 细胞提取物的 Western 印迹密度扫描显示，在所有使用的浓度下，与对照组相比，DZO 在 24 小时后降低了神经胶质纤维酸性蛋白（GFAP）的表达。此外，暴露于 10μM DZO 24 小时降低了微管蛋白和微管相关蛋白 1B（MAP1B）的水平。另一方面，DZO 处理对 MAP2c 的水平没有影响。与我们之前关于 DZ 的数据相反，上述发现表明，其氧代代谢物 DZO 可能在生物学相关的亚细胞毒性浓度下干扰神经胶质细胞分化。
