A new study from MIT has found that children may be far more vulnerable to NDMA — a cancer-causing chemical detected in contaminated drinking water and certain medications — than adults, with juvenile mice developing significantly higher rates of DNA damage and liver cancer after low-level exposure.
The research, published in Nature Communications, offers a potential scientific explanation for a troubling pattern observed in a real-world public health case: an elevated rate of childhood cancer in Wilmington, Massachusetts, where drinking water was contaminated with NDMA from the Olin Chemical site during the 1990s. Between 1990 and 2000, 22 children in Wilmington were diagnosed with cancer before the contaminated wells were shut down in 2003. The MIT findings now shed light on why young people may have been hit harder.
What Is NDMA and Where Does It Come From?
NDMA, or N-Nitrosodimethylamine, is a chemical compound that forms as a byproduct of many industrial chemical processes. It also appears in cigarette smoke and processed meats. In recent years, NDMA has been detected in certain formulations of common medications, including valsartan, ranitidine, and metformin.
Inside the body, NDMA is processed by a liver enzyme called CYP2E1. This metabolic process produces toxic byproducts that latch onto DNA, creating structural damage known as adducts — essentially chemical lesions that interfere with normal DNA function.
Why Children Face Higher Risk
The MIT researchers studied two groups of mice: three-week-old juveniles and three-month-old adults. Both groups drank water containing low levels of NDMA — about five parts per million — over two weeks.
When the team examined the livers of both groups, the initial DNA damage appeared similar. But what came next was dramatically different. In the juvenile mice, those initial DNA adducts triggered a cascade of double-stranded DNA breaks, which arose when cells attempted to repair the damage. These breaks then led to mutations — and ultimately, liver cancer. In the adult mice, the researchers observed virtually no double-stranded DNA breaks, far fewer mutations, and no severe liver pathology or tumor development.
“The initial structural changes to the DNA had very different consequences depending on age,” said Bevin Engelward, an MIT professor of biological engineering and the study’s senior author. “The double-stranded breaks were exclusively observed in the young.”
The key driver behind this difference turns out to be cell division speed. Cells in a juvenile liver divide rapidly, which means DNA damage gets copied and locked into mutations before the cell has a chance to fix it. Adult liver cells, by contrast, divide slowly — buying enough time for repair mechanisms to neutralize adducts before they become permanent mutations.
Testing Standards May Miss the Most Vulnerable
One of the study’s most pressing takeaways is a critique of how carcinogen safety testing is typically conducted. Standard toxicological studies use mice that are at least four to six weeks old — sometimes older — which the researchers argue misses the risk window for young animals and, by extension, children.
“With toxicological studies, oftentimes the standard is to use fully grown mice,” said Lindsay Volk, MIT postdoc and lead author of the paper. “At that point, they’re already slowing down cell division, so if we are testing the harmful effects of NDMA in adult mice, then we’re completely missing how vulnerable particular groups are, such as younger animals.”
Engelward echoed the urgency: “We really hope that groups that do safety testing will change their paradigm and start looking at young animals, so that we can catch potential carcinogens before people are exposed.”
Adults Are Not Completely Safe
The study is careful not to give adults a clean bill of health. Researchers found that when adult mice were treated with thyroid hormone — which stimulates liver cell proliferation — their cells accumulated mutations just as quickly as those in juvenile mice. Prior research from the Engelward laboratory also showed that inflammation can trigger increased cell division in the liver, raising vulnerability to DNA damage.
“Everything impacts your susceptibility to a carcinogen, whether that’s your genetics, your age, your diet, and so forth,” Volk noted. Conditions such as a high-fat diet, viral infection, or chronic alcohol use can accelerate cell division in the adult liver and potentially heighten sensitivity to NDMA.
While most cancer effects were observed in the liver — where NDMA is metabolized — a small number of mice in the study also developed lung cancer and lymphoma, suggesting the chemical’s reach may extend beyond just one organ.
What Comes Next
The research team is now investigating how a high-fat diet may influence the development of NDMA-related cancer in mice, a line of inquiry that could have significant implications for human health given rising rates of diet-related liver disease.
The study was funded by the National Institutes of Environmental and Health Sciences Superfund Research Program, a NIEHS Core Center Grant, a National Institutes of Health Training Grant, and the Anonymous Fund for Climate Action.
