Oxidative DNA damage in relation to neurotoxicity in the brain of mice exposed to arsenic at environmentally relevant levels
Oxidative DNA damage in relation to neurotoxicity in the brain of mice exposed to arsenic at environmentally relevant levels
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DOI：
10.1539/joh.47.445
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发表时间：
2005-09-01
影响因子：
3
通讯作者：
Yokoyama, K
中科院分区：
文献类型：
--
作者：
Piao, FY;Ma, N;Yokoyama, K
为了阐明DNA氧化损伤与砷的神经毒性之间的关系，用高效液相-电化学检测器和免疫组织化学方法，检测了饮用含1或2ppm砷的饮用水小鼠脑内DNA氧化损伤指标8-羟基-2‘-脱氧鸟苷(8-OHdG)的形成。染砷小鼠脑内8-OHdG水平明显升高，其免疫反应阳性物质主要分布在大脑和小脑皮质。大脑皮层神经元和小脑皮质浦肯野细胞呈退行性改变，与8-OHdG免疫反应阳性细胞的分布一致。本研究中的砷水平低于流行病学研究中报道的水平。因此，我们得出结论，环境相关水平的砷通过体内氧化损伤脑组织中的DNA而导致病理改变，大脑和小脑皮质神经元似乎是砷神经毒性的主要靶点。
To clarify the association between oxidative DNA damage and the neurotoxicity of arsenic, the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as an index of oxidative DNA damage in the brain was examined in mice fed with drinking water containing 1 or 2 ppm arsenic, using an HPLC-electrochemical detector and immunohistochemical method. 8-OHdG levels were significantly increased in the brain of mice given arsenic and its immunoreactivity was distributed in the cerebral and cerebellar cortexes. Cerebral cortex neurons and Purkinje cells in the cerebellar cortex showed degenerative changes in accordance with the distribution of 8-OHdG immunoreactivity. The levels of arsenic in this study were lower than those reported in epidemiological studies. Thus, we conclude that environmentally relevant levels of arsenic induce pathological changes through oxidative DNA damage in the brain tissues in vivo and that cerebral and cerebellar cortex neurons seem to be the major targets of arsenic neurotoxicity.