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Jinyao Mo,¹ Yajuan Xia,² Timothy J. Wade,³ Michael Schmitt,³ X. Chris Le,⁴ Runhe Dang,² and Judy L. Mumford ³

¹National Research Council, Washington, DC, USA; ²Inner Mongolia Center for Endemic Disease Control and Research, Huhhot, Inner Mongolia, China; ³National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; ⁴University of Alberta, Edmonton, Alberta, Canada

Abstract
Arsenic, a human carcinogen, is known to induce oxidative damage to DNA. In this study we investigated oxidative stress and As exposure by determining gene expression of OGG1, which codes for an enzyme, 8-oxoguanine DNA glycosylase, involved in removing 8-oxoguanine in As-exposed individuals.Bayingnormen (Ba Men) residents in Inner Mongolia are chronically exposed to As via drinking water. Water, toenail, and blood samples were collected from 299 Ba Men residents exposed to 0.34-826 µg/L As. RNA was isolated from blood, and mRNA levels of OGG1 were determined using real-time polymerase chain reaction. OGG1 expression levels were linked to As concentrations in drinking water and nails, selenium concentrations in nails, and skin hyperkeratosis. OGG1 expression was strongly associated with water As concentrations (p < 0.0001) . Addition of the quadratic term significantly improved the fit compared with the linear model (p = 0.05) . The maximal OGG1 response was at the water As concentration of 149 µg/L. OGG1 expression was also significantly associated with toenail As concentrations (p = 0.015) but inversely associated with nail Se concentrations (p = 0.0095) . We found no significant differences in the As-induced OGG1 expression due to sex, smoking, or age even though the oldest group showed the strongest OGG1 response (p = 0.0001) . OGG1 expression showed a dose-dependent increased risk of skin hyperkeratosis in males (trend analysis, p = 0.02) , but the trend was not statistically significant in females. The results from this study provide a linkage between oxidative stress and As exposure in humans. OGG1 expression may be useful as a biomarker for assessing oxidative stress from As exposure. Key words: arsenic, blood, humans, nail, OGG1, oxidative stress, selenium, skin hyperkeratosis. Environ Health Perspect 114:835-841 (2006) . doi:10.1289/ehp.8723 available via http://dx.doi.org/ [Online 9 February 2006]

Address correspondence to J.L. Mumford, MD 58C, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 USA. Telephone: (919) 966-0651. Fax: (919) 966-0655. E-mail: mumford.judy@epa.gov

We thank the participating members of the Inner Mongolia Center for Endemic Disease Control and Research and the Bayingnormen Anti-epidemic Station.

This research has been reviewed by the U.S. EPA and approved for publication. Approval does not signify that the contents reflect views of the agency or endorsement of the trade names mentioned.

The authors declare they have no competing financial interests.

Received 7 October 2005 ; accepted 9 February 2006.