Research from MIT indicates that a carcinogen present in certain medications and polluted drinking water may pose a greater threat to children than adults. The study on mice revealed that young mice exposed to this compound, NDMA, in drinking water exhibited significantly higher DNA damage and cancer rates compared to adults. This might clarify the link between childhood cancer and prenatal NDMA exposure in people near a contaminated site in Wilmington, Massachusetts, according to the researchers. The study highlights the importance of assessing carcinogen impacts across different ages.
“We hope safety testing groups will change their approach to include young animals, helping to identify carcinogens before public exposure,” said Bevin Engelward, an MIT biological engineering professor. Engelward emphasized the importance of cancer prevention over treatment. MIT postdoc Lindsay Volk led the paper, with Engelward as the senior author, published in Nature Communications.
NDMA, or N-Nitrosodimethylamine, is a byproduct of many industrial processes and is found in cigarette smoke and processed meats. It has been detected in drugs like valsartan, ranitidine, and metformin, and was found in Wilmington’s drinking water in the 1990s due to contamination from the Olin Chemical site. A 2021 Massachusetts Department of Health study suggested a link between this contamination and increased childhood cancer cases in Wilmington, with 22 cases diagnosed between 1990 and 2000. The contaminated wells were shut down in 2003.
Engelward and her team aimed to understand why NDMA affects children more than adults. Most carcinogen studies use mice aged 4 to 6 weeks or older. In this study, they tested two groups: 3-week-old juveniles and 3-month-old adults, both receiving water with low NDMA levels for two weeks. NDMA is metabolized into toxic compounds by the liver enzyme CYP2E1, leading to DNA damage.
Although both juvenile and adult mice showed similar DNA adduct levels, juveniles experienced more double-stranded DNA breaks, leading to liver cancer development. Adult mice had fewer breaks and mutations, with no severe liver pathology. “The initial DNA changes had vastly different effects based on age,” Engelward noted. Juvenile liver cells divide quickly, increasing mutation risks.
Volk highlighted the problem of using fully grown mice in toxicological studies, as they may not capture vulnerabilities in younger animals. While liver effects were prominent, some mice also developed lung cancer and lymphoma.
To expedite observing NDMA’s effects, researchers used mice with impaired DNA repair systems. However, even mice with normal DNA repair showed juvenile-specific NDMA-induced mutations, as their rapid cell growth encounters DNA adducts before repairs. Treating adult mice with thyroid hormone, which boosts liver cell proliferation, led to similar mutation rates as in juveniles.
Volk cautioned that adults are not immune to NDMA, as factors like genetics, age, diet, and health conditions can influence susceptibility. Adults with viral infections, high-fat diets, or chronic alcohol consumption might face increased NDMA vulnerability. Researchers are now examining how a high-fat diet impacts cancer development in NDMA-exposed mice. This study received funding from various National Institutes of Health and environmental research grants.
Original Source: news.mit.edu
