论文部分内容阅读
目的研究无机砷在体内甲基化代谢的主要产物二甲基胂酸(dimethylarsinic acid,DMA)在致肺肿瘤促进作用过程中是否诱发氧化应激。方法应用免疫组织化学方法和免疫电子显微镜胶体金染色法,检测400 ppm DMA经饮水给药0~25周,小鼠肺组织中脂质过氧化的主要代谢产物4-羟烯酸(4-hydroxy-2-nonenal,4HNE)的表达及定位。结果DMA给药25周,肺组织的姬姆(HE)染色与对照组比较未观察到明显的形态学改变。免疫组织化学方法检测到肺终末细支气管上皮细胞胞浆中有棕色颗粒的4HNE阳性染色,染色细胞数明显高于对照组(P<0.05)。从DMA给药8周开始4HNE阳性染色细胞数随给药时间延长而增多,并且与对照组比较,差异有统计学意义(P<0.05)。免疫电子显微镜胶体金染色法观察到肺终末细支气管上皮细胞中呈阳性染色的为无纤毛的Clara细胞。DMA给药导致小鼠肺Clara细胞发生滑面内质网扩张、增生及核周水肿等超微结构的形态学改变。结论口服DMA诱发氧化应激,并且在DMA诱发肿瘤促进作用过程中一直起着十分重要的作用。我们首次指出,口服DMA致小鼠肺肿瘤促进作用过程中,DMA诱发的氧化应激特异地发生在肺肿瘤的靶细胞Clara细胞。
Objective To investigate whether dimethylarsinic acid (DMA), a major product of inorganic arsenic methylation in vivo, induces oxidative stress in the process of promoting lung tumor. Methods The expression of 4-hydroxy-4-hydroxybutyric acid (4-hydroxybutyric acid), a major metabolite of lipid peroxidation in mouse lung tissue, was detected by immunohistochemical staining and immunogold electron microscopy -2-nonenal, 4HNE) expression and localization. Results After administration of DMA for 25 weeks, no significant morphological changes were observed in the lung tissue after HE staining compared with the control group. 4HNE positive staining of brown particles in the cytoplasm of bronchial epithelial cells of lung terminal was detected by immunohistochemical staining, and the number of stained cells was significantly higher than that of the control group (P <0.05). The number of 4HNE positive staining cells increased from the 8th week after administration of DMA, and the difference was statistically significant (P <0.05) compared with the control group. Immuno-electron microscopy colloidal gold staining of pulmonary terminal bronchial epithelial cells were observed positive staining of cilia-free Clara cells. DMA administration led to morphological changes in the ultrastructure of mouse pulmonary Clara cells such as dilated endoplasmic reticulum, hyperplasia and perinuclear edema. Conclusions Oral DMA induces oxidative stress and plays a very important role in the process of DMA-induced tumorigenesis. We first pointed out that DMA-induced oxidative stress specifically occurs in Clara cells, a target cell in lung tumors, during oral administration of DMA to promote lung tumor in mice.