Arsenic affects on cerebellar development of mice.

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.