Specific induction of oxidative stress in terminal bronchiolar Clara cells during dimethylarsenic-induced lung tumor promoting process in mice
Specific induction of oxidative stress in terminal bronchiolar Clara cells during dimethylarsenic-induced lung tumor promoting process in mice
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DOI：
10.1016/j.canlet.2004.12.029
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发表时间：
2005-12-08
期刊：
影响因子：
9.7
通讯作者：
Yamanaka, K
中科院分区：
文献类型：
--
作者：
An, Y;Kato, K;Yamanaka, K
应用免疫组织化学方法，研究了无机砷在哺乳动物体内的主要代谢产物二甲基胂酸（DMA）在肺肿瘤促发过程中对肺细胞氧化应激的诱导作用。我们证明，4HNE修饰的蛋白质特异性地存在于终末细支气管Clara细胞的分泌颗粒中。此外，阳性染色的程度随着DMA给药的持续时间而增加。透射电子显微镜显示DMA处理小鼠的Clara细胞的形态学变化。这些结果表明，Clara细胞是DMA诱导的氧化应激的主要靶细胞，并且该细胞可能在小鼠肺肿瘤促进过程中起重要作用。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
The induction of oxidative stress in pulmonary cells during the process of lung tumor promotion by dimethylarsinic acid (DMA), a main metabolite of inorganic arsenics in mammals, was examined by immunohistochemical analysis using a specific antibody against 4-hydroxy-2-nonenal (4HNE) adducts, which are major aldehydic metabolites of lipid peroxidation. We demonstrated that 4HNE-modified proteins existed specifically in the secretory granules in terminal bronchiolar Clara cells. Furthermore, the degree of positive staining increased with the duration of DMA administration. Transmission electron microscopy revealed morphological changes in the Clara cells of DMA-treated mice. These results suggest that Clara cells are the major target cell for DMA-induced oxidative stress and that the cells may play an important role in the lung tumor promotion process in mice. (c) 2005 Elsevier Ireland Ltd. All rights reserved.