Public health experts estimate that more than 200 million people worldwide are exposed to arsenic through contaminated drinking water. Scientists know that long-term exposure to arsenic is associated with an increased risk of chronic diseases such as cancer and cardiovascular disease, but there is still no reliable way to track these exposures and fully understand their effects on the body and the mechanisms behind them.
A new study led by researchers at the University of Chicago addresses this challenge, revealing how arsenic leaves traces in human DNA and providing a potential new tool for exposure assessment. in International Journal of Epidemiologyresearchers describe a powerful DNA methylation-based biomarker associated with arsenic exposure. This biomarker serves as a model for developing other epigenetic biomarkers that can help predict toxicity risk and track and potentially mitigate the health effects of environmental toxins.
Study large, highly exposed populations
Researchers analyzed blood samples from more than 1,100 Bangladeshi adults. Arsenic contamination in well water is a serious and persistent public health challenge in Bangladesh. The research team used an advanced DNA methylation array to scan more than 700,000 sites across the genome, searching for patterns that correlated with arsenic levels measured in the participants’ urine.
This was a huge leap forward in scale and resolution. Because of our large sample size and wide range of exposure levels, we were able to identify more epigenomic sites associated with arsenic exposure than previous studies in adults. ”
James Li, PhD, senior study author and MD/PhD student, University of Chicago
The research team found 1,177 sites in the genome that were significantly associated with arsenic exposure, most of which had not been previously identified. Going a step further, they employed an analytical approach called Mendelian randomization to assess whether arsenic exposure was playing a role. causally It not only shows a correlation but also influences DNA methylation at these sites in the epigenome. This type of statistical analysis is important because there is no ethical way to study something as potentially harmful as arsenic exposure in traditional randomized trials.
“Mendelian randomization helped us rule out other variables, allowing us to say not only that arsenic and DNA methylation are related, but that the way someone’s body metabolizes arsenic is likely to cause these changes in DNA methylation,” said senior author Dr. Brandon Pierce, incoming dean of the University of California School of Public Health Sciences.
Development and validation of epigenetic biomarkers
The researchers then set out to distill the genome-wide findings into measurable signatures of DNA methylation that could estimate an individual’s arsenic exposure from blood samples. Using the 255 sites they identified, they were able to reliably predict urinary arsenic levels, arsenic-induced skin lesions (wounds that are clinically visible signs of how arsenic poisons the body), and overall mortality.
“The half-life of arsenic in the body after drinking contaminated water is relatively short, so exposure levels measured in urine samples can be variable,” Lee said. “Changes in DNA methylation are thought to be more stable, so building biomarkers will allow us to obtain more information about long-term biological effects.”
This biomarker proved predictive beyond the original Bangladeshi cohort. When tested in a completely different population in the United States, where overall arsenic exposure is much lower, the researchers were still able to estimate arsenic exposure, albeit with less precision. To date, it has proven to be the best performing epigenetic marker for single toxin exposure, including those developed for alcohol consumption and lead exposure.
“We were surprised that this predictor worked so well, even in a completely different population with much lower exposures,” Pearce said. “This gives us hope that epigenetic biomarkers are a promising tool for estimating historical exposure to environmental chemicals.”
Many of the genomic regions that the researchers identified as most closely associated with arsenic exposure matched very closely with regions previously associated with chronic diseases such as heart disease, type 2 diabetes, and various cancers, and were consistent with known health effects associated with arsenic exposure.
“Although we have not conclusively proven that DNA methylation directly causes these downstream health effects, we provide very strong evidence that these epigenetic changes may help explain the association between arsenic and related health conditions,” Lee said.
Pearce added: “This is an important reminder that environmental exposures actually ‘get under the skin’ and leave their mark on you through changes in genome function.”
sauce:
University of Chicago Medical Center
Reference magazines:
Lee, J.L., et al. (2026). Effects of arsenic exposure on human DNA methylation: Construction of epigenetic biomarkers of exposure across three independent cohorts. International Journal of Epidemiology. DOI: 10.1093/walk/dyag056. https://academic.oup.com/ije/article-abstract/55/3/dyag056/8664521.
