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. 2006 Jun;114(6):835-41.
doi: 10.1289/ehp.8723.

Chronic arsenic exposure and oxidative stress: OGG1 expression and arsenic exposure, nail selenium, and skin hyperkeratosis in Inner Mongolia

Jinyao Mo  1 , Yajuan Xia, Timothy J Wade, Michael Schmitt, X Chris Le, Runhe Dang, Judy L Mumford
Affiliations

Chronic arsenic exposure and oxidative stress: OGG1 expression and arsenic exposure, nail selenium, and skin hyperkeratosis in Inner Mongolia

Jinyao Mo et al. Environ Health Perspect. 2006 Jun.

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 microg/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 microg/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.

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Figures

Figure 1
Figure 1
Map of three counties in Ba Men where residents have been chronically exposed to As via drinking water. The study sites are located at Sha Hai Village in Hangjin Hou County and Sheng Feng Village in Wu Yuan County.
Figure 2
Figure 2
Frequency distribution of study subjects according to As concentrations of well water (n = 299).
Figure 3
Figure 3
High correlation between nail and water As concentrations (n = 299; Spearman r = 0.8816; p < 0.0001; nail As = 1.135 + 0.04277 × water As).
Figure 4
Figure 4
Association between OGG1 mRNA levels and water As concentrations (n = 299) by linear (A) and quadratic (B) modeling. OGG1 mRNA levels and water As for the subjects were all normalized to β-actin levels, multiplied by 100, and log transformed. (A) OGG1 mRNA concentrations were positively associated with water As concentrations using the linear model [Spearman r = 0.24; p < 0.0001; OGG1 × 100(log) = 2.10 + 0.054 × water As(log)]. (B) OGG1 mRNA concentrations were positively associated with water As concentrations using the quadratic model [adjusted r = 0.24; p < 0.0001; OGG1 × 100(log) = 2.05 + 0.15 × water As(log) – 0.035 × water As(log)2].
Figure 5
Figure 5
Effect of age on As-induced OGG1 expression for three age groups: (A) 11–18 years of age [n = 54; Spearman r = 0.37; p = 0.0062; OGG1 × 100(log) = 2.05 + 0.075 × water As(log)]; (B) 19–50 years of age [n = 196; Spearman r = 0.16; p = 0.03; OGG1 × 100(log) = 2.12 + 0.038 × water As(log)]; (C) 51–60 years of age [n = 48; Spearman r = 0.54; p = 0.0001; OGG1 × 100(log) = 2.07 + 0.099 × water As(log)].
Figure 6
Figure 6
Association between OGG1 expression and nail As and nail Se concentrations. (A) Positive association between OGG1 expression and nail As concentration [n = 299; Pearson r = 0.14; p = 0.015; OGG1 × 100(log) = 2.15 + 0.054 × nail As(log)]. (B) Negative association between OGG1 expression and nail Se concentrations [n = 288; Spearman r = –0.16; p = 0.0095; OGG1 × 100(log) = 2.26 – 1.35 × nail Se].
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