Elevated ERCC1 gene expression in blood cells associated with exposure to arsenic from drinking water in Inner Mongolia.

BACKGROUND: Chronic arsenic exposure has been associated with human cancer. The objective of this study was to investigate the effects of arsenic exposure on a DNA nucleotide excision repair gene, ERCC1, expression in human blood cells. PATIENTS AND METHODS: Water and toenail samples were collected from a total of 327 Inner Mongolian residents for arsenic analysis. Blood samples were collected to determine mRNA expression levels by real-time PCR. RESULTS: The mRNA levels of ERCC1 expression were positively associated with water arsenic concentration (slope=0.313, p=0.0043) and nail arsenic concentration (slope=0.474, p=0.0073). mRNA levels of ERCC1 expression were significantly correlated with those of OGG1, a base pair excision repair gene (r=0.275, p<0.0001). CONCLUSION: The results showed that mRNA levels of ERCC1 expression were significantly associated with arsenic concentrations in drinking water, implicating the DNA repair response was induced by arsenic exposure.

Well water arsenic exposure, arsenic induced skin-lesions and self-reported morbidity in Inner Mongolia.

Residents of the Bayingnormen region of Inner Mongolia have been exposed to arsenic-contaminated well water for over 20 years, but relatively few studies have investigated health effects in this region. We surveyed one village to document exposure to arsenic and assess the prevalence of arsenic-associated skin lesions and self-reported morbidity. Five-percent (632) of the 12,334 residents surveyed had skin lesions characteristics of arsenic exposure. Skin lesions were strongly associated with well water arsenic and there was an elevated prevalence among residents with water arsenic exposures as low as 5 microg/L-10 microg/L. The presence of skin lesions was also associated with self-reported cardiovascular disease.

Increased mortality associated with well-water arsenic exposure in Inner Mongolia, China.

We conducted a retrospective mortality study in an Inner Mongolian village exposed to well water contaminated by arsenic since the 1980s. Deaths occurring between January 1, 1997 and December 1, 2004 were classified according to underlying cause and water samples from household wells were tested for total arsenic. Heart disease mortality was associated with arsenic exposure, and the association strengthened with time exposed to the water source. Cancer mortality and all-cause mortality were associated with well-water arsenic exposure among those exposed 10-20 years. This is the first study to document increased arsenic-associated mortality in the Bayingnormen region of Inner Mongolia.

Elevated human telomerase reverse transcriptase gene expression in blood cells associated with chronic arsenic exposure in Inner Mongolia, China.

BACKGROUND: Arsenic exposure is associated with human cancer. Telomerase-containing human telomerase reverse transcriptase (hTERT) can extend telomeres of chromosomes, delay senescence, and promote cell proliferation leading to tumorigenesis. OBJECTIVE: The goal of this study was to investigate the effects of As on hTERT mRNA expression in humans and in vitro. METHOD: A total of 324 Inner Mongolia residents who have been exposed to As via drinking water participated in this study. Water and toenail samples were collected and analyzed for As. Blood samples were quantified for hTERT mRNA expression using real-time polymerase chain reaction. The hTERT mRNA levels were linked to water and nail As concentrations and skin hyperkeratosis. Human epidermal keratinocytes were treated with arsenite to assess effects on cell viability and hTERT expression in vitro. RESULTS: hTERT mRNA expression levels were significantly associated with As concentrations of water (p<0.0001) and nails (p=0.002) and also associated with severity of skin hyperkeratosis (p<0.05), adjusting for age, sex, smoking, and pesticide use. Females showed a higher slope than males (females: 0.126, p=0.0005; males: 0.079, p=0.017). In addition to water and nail As concentrations, age (p<0.0001) and pesticide use (p=0.025) also showed significant associations with hTERT expression. The hTERT expression levels decreased with age. Tobacco smoking did not affect hTERT expression (p=0.13). hTERT expression was significantly correlated with OGG1 and ERCC1 expression. The in vitro results also showed a dose-response relationship between arsenite concentrations and hTERT expression and reached the peak at 1 microM. CONCLUSIONS: hTERT expression was associated with As exposure in vivo and in vitro. The increased hTERT expression may be a cellular response to genomic insults by As and may also indicate that As may function as a tumor promoter in carcinogenesis in humans.

Residential exposure to drinking water arsenic in Inner Mongolia, China.

In the Ba Men region of Inner Mongolia, China, a high prevalence of chronic arsenism has been reported in earlier studies. A survey of the arsenic contamination among wells from groundwater was conducted to better understand the occurrence of arsenic (As) in drinking water. A total of 14,866 wells (30% of all wells in the region) were analyzed for their arsenic-content. Methods used to detect arsenic were Spectrophotometric methods with DCC-Ag (detection limit, 0.5 microg of As/L); Spot method (detection limit, 10 microg of As/L); and air assisted Colorimetry method (detection limit, 20 microg of As/L). Arsenic-concentrations ranged from below limit of detection to 1200 microg of As/L. Elevated concentrations were related to well depth (10 to 29 m), the date the well was built (peaks from 1980-1990), and geographic location (near mountain range). Over 25,900 individuals utilized wells with drinking water arsenic concentrations above 20 microg of As/L (14,500 above 50 microg of As/L-the current China national standard in drinking water and 2198 above 300 microg of As/L). The presented database of arsenic in wells of the Ba Men region provides a useful tool for planning future water explorations when combined with geological information as well as support for designing upcoming epidemiological studies on the effects of arsenic in drinking water for this region.

Neurosensory effects of chronic exposure to arsenic via drinking water in Inner Mongolia: II. Vibrotactile and visual function.

This study was designed to assess the effects of exposure to arsenic in drinking water on visual and vibrotactile function in residents of the Bamen region of Inner Mongolia, China. Arsenic was measured by hydride generation atomic fluorescence. 321 participants were divided into three exposure groups- low (non-detectable-20), medium (100-300) and high (400-700 microg/l) arsenic in drinking water (AsW). Three visual tests were administered: acuity, contrast sensitivity and color discrimination (Lanthony's Desaturated 15 Hue Test). Vibration thresholds were measured with a vibrothesiometer. Vibration thresholds were significantly elevated in the high exposure group compared to other groups. Further analysis using a spline regression model suggested that the threshold for vibratory effects is between 150-170 microg/l AsW. These findings provide the first evidence that chronic exposure to arsenic in drinking water impairs vibrotactile thresholds. The results also indicate that arsenic affects neurological function well below the 1000 microg/I concentration reported by NRC (1999). No evidence of arsenic-related effects on visual function was found.

Neurosensory effects of chronic exposure to arsenic via drinking water in Inner Mongolia: I. Signs, symptoms and pinprick testing.

This study was designed to assess the effects of exposure to arsenic in drinking water on neurosensory function. A questionnaire including neurological signs and symptoms and a brief neurological exam consisting of pinprick testing of the arms and legs and knee-jerk test were administered to 321 residents of the Bamen region of Inner Mongolia, China. Arsenic in water was measured by hydride generation atomic fluorescence. Participants were divided into three exposure groups--low (non-detectible-20), medium (100-300) and high (400-700 microg/I) arsenic. Significant group differences were observed in pinprick scores for all four limbs. Results indicate that arsenic alters pinprick (pain) thresholds at well-water concentrations as low as 400 microg/l, well below the 1000 microg/l threshold for neurological effect specified by NRC (1999). Regression models suggest that a 50% increase in pinprick score is associated with a 71-159 ppb increase in arsenic concentration.