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J Occup Health year 2005 volume 47 number 5 page 445 - 449
Classification Original
Title Oxidative DNA Damage in Relation to Neurotoxicity in the Brain of Mice Exposed to Arsenic at Environmentally Relevant Levels
Author Fengyuan PIAO1, Ning MA2, Yusuke HIRAKU3, Mariko MURATA3, Shinji OIKAWA3,
Fanyin CHENG4, Laifu ZHONG1, Toru YAMAUCHI5, Shosuke KAWANISHI3 and
Kazuhito YOKOYAMA5
Organization 1Department of Hygiene, 4Department of Health administration, Dalian Medical University, P.R. China, 2The Second Department of Anatomy, 3Department of Environmental and Molecular Medicine, 5Department of Public Health and Occupational Medicine, Graduate School of Medicine, Mie University, Japan
Keywords Arsenic trioxide, 8-Hydroxy-2'-deoxyguanosine (8-OHdG), Cerebral cortex, Cerebellar cortex, Purkinje cell, Oxidative DNA damage
Correspondence F. Piao, Department of Hygiene, Dalian Medical University, Zhongshan Avenue, Dalian 116027, P.R. China (e-mail: piaofy_dy@yahoo.com.cn)
Abstract Oxidative DNA Damage in Relation to Neurotoxicity in the Brain of Mice Exposed to Arsenic at Environmentally Relevant Levels: Fengyuan PIAO, et al. Department of Hygiene, Dalian Medical University, China-To clarify the association between oxidative DNA damage and the neurotoxicity of arsenic, the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as an index of oxidative DNA damage in the brain was examined in mice fed with drinking water containing 1 or 2 ppm arsenic, using an HPLC-electrochemical detector and immunohistochemical method. 8-OHdG levels were significantly increased in the brain of mice given arsenic and its immunoreactivity was distributed in the cerebral and cerebellar cortexes. Cerebral cortex neurons and Purkinje cells in the cerebellar cortex showed degenerative changes in accordance with the distribution of 8-OHdG immunoreactivity. The levels of arsenic in this study were lower than those reported in epidemiological studies. Thus, we conclude that environmentally relevant levels of arsenic induce pathological changes through oxidative DNA damage in the brain tissues in vivo and that cerebral and cerebellar cortex neurons seem to be the major targets of arsenic neurotoxicity.