Histology and Embryology Department, Shenyang Medical College , Shenyang , China.
Toxicol Mech Methods. 2013 Nov;23(9):672-7. doi: 10.3109/15376516.2013.840347. Epub 2013 Sep 27.
To evaluate arsenic affects on the development of cerebellum, the mother mice received drinking water containing arsenic trioxide (As2O3) 4 ppm during gestation and lactation period. The cytogenesis was observed by immunohistochemical technique using 5'-bromo-2'-deoxyuridine (BrdU) antibody. To characterize the arsenic neurotoxicity, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidative DNA lesion marker, and 8-nitroguanine, a nitrative DNA lesion marker were used to verify DNA damage. Arsenic-exposed litters showed neuron necrosis. The mitosis of granule cells decreased dramatically in arsenic-exposed mice as compared with arsenic unexposed mice. 8-OxodG was formed in neurons of all the layers, especially in the granular layer in cerebellum of arsenic-exposed mice. There is no significant difference, however, in the expression of 8-nitroguanine between arsenic-exposed and -unexposed mice. These results indicate that arsenic can disturb the mitosis of granule cells and interfere with the normal development of mice cerebellum. Arsenic-induced pathological changes in vivo may be caused by oxidative DNA damage other than nitrative DNA damage.
为了评估砷对小脑发育的影响，母鼠在妊娠期和哺乳期摄入浓度为 4ppm 的三氧化二砷（As2O3）饮用水。通过使用 5'-溴-2'-脱氧尿苷（BrdU）抗体的免疫组织化学技术观察细胞发生情况。为了表征砷的神经毒性，使用 8-氧代-7,8-二氢-2'-脱氧鸟苷（8-oxodG），一种氧化 DNA 损伤标志物，和 8-硝基鸟嘌呤，一种硝化 DNA 损伤标志物来验证 DNA 损伤。暴露于砷的后代显示出神经元坏死。与未暴露于砷的小鼠相比，暴露于砷的小鼠的颗粒细胞有丝分裂明显减少。8-oxodG 形成于所有层的神经元中，特别是在暴露于砷的小鼠的小脑颗粒层中。然而，暴露于砷和未暴露于砷的小鼠之间 8-硝基鸟嘌呤的表达没有显著差异。这些结果表明，砷可以干扰颗粒细胞的有丝分裂并干扰小鼠小脑的正常发育。体内砷引起的病理变化可能是由氧化 DNA 损伤而不是硝化 DNA 损伤引起的。
