Cancer-linked chemical in water and meds may pose a higher risk to children

The biggest threat to your child's health is perhaps lurking in your kitchen’s tap. A groundbreaking study suggests that a carcinogen found in contaminated water and some medications may have a more severe impact on young children than adults.A new study by Massachusetts Institute of Technology researchers found that the chemical NDMA is much more likely to cause cancerous mutations after exposure early in life. The findings are published in Nature Communications.The MIT researchers found that NDMA (N-Nitrosodimethylamine), generated as a byproduct of many industrial chemical processes, has been found in some medications and in drinking water contaminated by chemical plants, and can cause dramatically higher rates of DNA damage and cancer in juvenile mice than adults. This chemical is also found in cigarette smoke and processed meats. The study's findings may explain the link between childhood cancer and prenatal exposure to NDMA in people living near a contaminated site in Wilmington, Massachusetts. This study is also crucial in evaluating the impact of potential carcinogens across all ages.“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. As a solution to cancer, cancer prevention is clearly much better than cancer treatment, so we hope we can spot dangerous chemicals before people are exposed, and therefore prevent extensive cancer risk,” Bevin Engelward, an MIT professor of biological engineering and senior author of the study, said in a release.NDMA (N-Nitrosodimethylamine) is often generated as a byproduct of many industrial chemical processes. In recent years, this chemical has been detected in some formulations of the drugs valsartan, ranitidine, and metformin. This chemical was also detected in drinking water in Wilmington, Massachusetts, in the 1990s, due to contamination from the Olin Chemical site.Back in 2021, the MIT study suggested a link between that water contamination and an elevated incidence of childhood cancer in Wilmington. Twenty-two children from the area were diagnosed with cancer between 1990 and 2000. Later in 2003, the contaminated wells were closed.In 2021, Engelward and others at MIT published a study on the mechanism of how NDMA can lead to cancer. In the new study, the researchers looked into why this chemical compound affected children more than adults.The studyThe researchers studied two groups of mice: one 3 weeks old (juvenile), and one 6 months old (adult). Both groups were given drinking water with low levels of NDMA, about five parts per million, for two weeks.The NDMA is metabolized by a liver enzyme called CYP2E1 in the body. It produced toxic metabolites that can damage DNA by adding a small chemical group known as a methyl group to DNA bases, creating lesions known as adducts.The livers of the juveniles and adults showed similar levels of DNA adducts. But there were dramatic differences in what happened after that initial damage. In juvenile mice, the DNA adducts led to significant accumulation of double-stranded DNA breaks, which occur when cells try to repair adducts. These breaks produce mutations that eventually lead to the development of liver cancer.On the other hand, in adult mice, there were essentially no double-stranded breaks and significantly fewer mutations compared to juveniles. The livers did not develop severe pathology, including tumors, even though they experienced the same initial level of DNA adducts.“The initial structural changes to the DNA had very different consequences depending on age. The double-stranded breaks were exclusively observed in the young,” Engelward said.More experiments showed that these differences stemmed from differences in the rates of cell proliferation. Cells in the juvenile liver divide rapidly, leading to more mutations compared to the cells of adult liver that rarely divide.“This really emphasizes the overall problem that we’re trying to highlight in the paper. With toxicological studies, oftentimes the standard is to use fully grown mice. 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,” MIT postdoc Lindsay Volk is the lead author of the paper, said.A few of the mice also developed other types of cancer, including lung cancer and lymphoma.The risk of NDMA exposure surely affects adults. “We certainly don’t want to say that adults are completely resistant to NDMA. Everything impacts your susceptibility to a carcinogen, whether that’s your genetics, your age, your diet, or so forth. In adults, if they have a viral infection, or a high fat diet, or chronic binge alcohol drinking, this can impact proliferation within the liver and potentially make them susceptible to NDMA,” Volk said.The researchers are now investigating how a high-fat diet might influence cancer development in mice exposed to NDMA.