Superfund Research Program
Arsenic Exposure and Human Health
Although the new Maximum Contaminant Level (MCL) for arsenic is 10 parts per billion (ppb), the EPA estimates that approximately 350,000 people in the United States drink water containing more than 50 ppb, and nearly 25 million people drink water containing more than 25 ppb. In Bangladesh, where levels of 1-2 part per million (ppm) are not uncommon, arsenic in ground water poses a public health hazard with tremendous impact on people's lives, health, social, and economic activities.
The health effects of exposure to high levels of arsenic are significant and well documented. However, the impact of low to moderate level exposures remains unclear. Since 1995, Superfund Basic Research Program investigators led by Dr. David Christiani at the Harvard School of Public Health have studied biomarkers of exposure to arsenic and heritable susceptibility in two populations. One of the populations is in Taiwan, where remediation efforts have resulted in a reduction in arsenic exposure to ranges of one to three-fold more than those observed in most US communities. A second population is in Bangladesh, in an area recently described as having extremely high exposures from drinking water contamination. The researchers are utilizing a population-based approach, incorporating markers of exposure (drinking water arsenic, toenail arsenic, and measures of inorganic arsenic in urine), susceptibility (genetic polymorphisms in metabolizing genes), and outcome (squamous cell carcinoma of the skin, bladder cancer, and non-malignant skin lesions). These studies are designed to fill important research gaps in our understanding of arsenic and human health.
As part of this research, Dr. Christiani's team developed field collection methods for accurately measuring different arsenic species in urine. Prior to this work, it was not known how stable the arsenic species are in human urine collected in field studies. The Harvard research team designed a series of experiments to examine arsenic species stability in urine. They found that the urinary matrix plays an important role in stabilizing arsenic species, and that even simple preparation techniques such as centrifugation result in a loss of arsenic and underestimation of exposure. Moreover, after approximately three months of storage, urine arsenic species undergo conversion spontaneously. As a result of these findings, they developed a protocol for the collection, storage and analysis of urinary arsenic compounds for epidemiologic studies.
Dr. Christiani is currently conducting studies in the Pabna region of Bangladesh, where the population obtains drinking water through tube wells, and arsenic levels in drinking water are reported to range from safe levels to several orders of magnitude higher than the World Health Organization and Bangladesh drinking water standards. In addition to studying the impact on health status including cumulative arsenic exposure, age, gender, and diet, they will examine the effect of gene polymorphisms in the Glutathione S-transferase (GST) superfamily of enzymes, which plays an active role in arsenic metabolism processes.
Dr. Christiani's analyses of bladder and skin cancer in Taiwan revealed that:
- A person's ability to metabolize inorganic arsenic into less toxic metabolites (monomethylarsonic acid [MMA] and dimethylarsinic acid [DMA]) is directly related to the risk of both bladder and skin cancer. Methylation of DMA to MMA plays an important role in lowering, but not eliminating, the risk of skin and bladder cancer. Methylation of inorganic arsenic to DMA exhibits a weak effect in the opposite direction.
- In cases with similar methylation abilities and cumulative arsenic exposures, men had a higher risk of skin cancer, suggesting that additional behavioral or genetic factors may play a role.
- There is a significant relationship between smoking status, cumulative arsenic exposure, and increased risk of bladder cancer
- The risk of developing skin cancer after long-term exposure to arsenic in drinking water was enhanced by certain genetic characteristics, most significantly by variation at codon 72 of the tumor suppressor gene p53.
These findings have important public health significance. At the same level of exposure, some persons are at higher risk of cancer development than are others. Efforts to protect the more susceptible among us will ensure protection for all.
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To learn more about this research, please refer to the following sources:
- Chen Y, Guo YL, Su HJ, Hsueh Y, Smith TJ, Ryan LM, Lee M, Chao S, Lee YY, Christiani DC. 2003. Arsenic methylation and skin cancer risk in southwestern Taiwan. J Occup Environ Med 45(3):241-248. PMID:12661181
- Chen Y, Xu L, Guo YL, Su HJ, Hsueh Y, Smith TJ, Ryan LM, Lee M, Chao S, Lee J, Christiani DC. 2003. Genetic polymorphisms in p53 codon 72 and skin cancer in southwestern Taiwan. J Environ Sci Health A Tox Hazard Subst Environ Eng 38(1):201-211. doi:10.1081/ESE-120016889 PMID:12635827
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