Abnormal expression of 8-nitroguanine in the brain of mice exposed to arsenic subchronically

Abstract

To provide molecular toxicological evidences for exploring the mechanism of arsenicinduced neurotoxicity the accumulation of arsenic (As), the formation of 8-nitroguanine (8-NO2-G) were examined in brain tissue of mice exposed to arsenic. And the gene expressions of inducible NOS (iNOS), superoxide dismutase 1 (SOD1) and peroxiredoxin 2 (Prdx2) were also analyzed by GeneChip. In the result, the concentration of As in the brain tissue of mice was 4.00, 13.70, 21.48 and 29.88 ng/g in the controls and experimental groups exposed to 1, 2 and 4 mg/l As2O3, respectively and increased in dose-response manner. Nervous cells in the brain of mice exposed to As showed disappearances of axons, vacuolar degeneration in cytoplasm and karyolysis, whereas no such pathological changes were observed in the control group. Weak immunoreactivity against 8-NO2-G was observed in the brain tissue of mice given 1 or 2 ppm arsenic trioxide. More intensive immunoreactivity was found in cells at 4 ppm and it was mainly distributed in cytoplasm. The expressions of SOD1 and Prdx2 were down-regulated in the brain of mice exposed to As, but iNOS expression was not disturbed by As exposure. No the 8-NO2-G immunoreactivity or abnormal expressions of these genes in brain tissue were observed in controls. These results indicate that As induces high expression of 8-NO2-G in brain tissues of mice and that RNA in the cells may be modified by overproduced reactive nitrogen species.