Epidemiological Study links NDMA to Cancer
Wilmington Massachusetts is a leafy suburb just north of Boston. With classic New England homes and maple trees it provides an idyllic setting for family life. Nevertheless, in the 1990s, mothers started noticing that many of their children had cancer. When a proper study was done, it was discovered that 24 children out of a town of approximately 18,000 had cancer, which is six times higher than the national average. People living in Wilmington wanted to know what had caused so many cases of childhood cancer in their town, and they turned their attention to their drinking water. Knowing that the Olin chemical company had operated in Wilmington for many years, and that the site was used for many other chemical companies prior to Olin, town members wondered if it was possible that chemical waste had made its way from the Olin site to their drinking water wells.
When town members went to local officials to express their concern about the safety of their drinking water, their concerns were largely dismissed, and they were told that their water was safe. However, local residents did not give up. Remarkably, residents combed through historic documents trying to figure out if dangerous chemicals could have made their way into their water. They learned that in fact, chemical waste had been dumped into unlined pools and lagoons adjacent to the factory raising the possibility that millions of gallons of waste may have seeped into the earth. With no formal training in chemistry, Debbie Duggan and Suzanne Sullivan started wondering if N-nitrosodimethylamine (NDMA) was in their water. They were worried about NDMA because it was well-established that NDMA is a potent carcinogen in animal models. They insisted that the town well water be tested for the presence of NDMA. When testing was finally done, it was discovered that indeed, NDMA was in the town well water that had been drunk by thousands of people for many years.
Although officials did not necessarily agree that NDMA had been a health problem, the wells were nevertheless closed in 2003. Soon thereafter, concerned about contaminated municipal water, the EPA designated the Olin site as a Superfund site. However, people living in Wilmington wanted more research. They wanted a public health study to be done to determine if NDMA was linked to cancer in their children. The study took quite some time.
Meanwhile, there was a serendipitous event. At a committee meeting at MIT, J. E. From Wilmington mass met John Essigmann, a well-recognized Prof. of toxicology and chemistry. She explained to Prof. Essigmann that people living in Wilmington were worried that a Superfund site was responsible for a childhood cancer cluster. When she said that the primary concern was NDMA, Prof. Essigmann was stunned. NDMA is a chemical that is closely related to other chemicals that he had been studying for more than 20 years. Furthermore, there were nearly half a dozen other faculty at MIT who also were studying chemicals related to NDMA. This gave Prof. Essigmann the idea that perhaps a team could be assembled to address the needs of the community and so he recruited fellow faculty and other leaders to put forth the concept of a new Superfund research program at MIT. At a meeting with William Suk and Michelle Heacock (Director and member of the NIEHS Superfund research program leadership team, respectively), the MIT team was encouraged to apply for a Superfund grant. In 2017, the MIT Superfund research program was created with Prof. Bevin Engelward and Prof. John Essigmann as the director, and codirector of the program. Later, Noelle Selin agreed to contribute as a codirector.
The focus of the MIT Superfund research program is on alkylating agents. These are chemicals that create adducts on DNA, disrupting its structure and thus promoting mutagenesis and toxicity. In particular, the MIT team studies NDMA and polycyclic aromatic hydrocarbons (PAHs). In terms of NDMA, the team has made progress in creating sensors. Dr. Maggie He, member of the swagger lab, created a carbon nanotube sensor for NDMA in air. More recently, Jessica Beard from the Swagger lab has been developing a sensor for NDMA in water. In parallel, biologists applied their skills to study the mutagenic and carcinogenic effects of NDMA, with an emphasis on gene environment interactions that might modulate susceptibility. Jennifer Kay, Joshua Corrigan, and Amanda Armijo (from the Engelward and Essigmann laboratories) made the discovery that a particular DNA repair enzyme has a profound effect on the biological consequences of NDMA. (See https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00178-9) When too low, animals suffer from DNA damage induced mutations in cancer, and when too high, animals suffer from DNA damage induced toxicity. This remarkable discovery paves the way for human studies, wherein the role of this repair enzyme can be studied in terms of its relationship to vulnerability to NDMA exposure.
Meanwhile, the epidemiological study of NDMA performed by the Massachusetts Department of Public Health was finally released some 20 years since the time when NDMA was discovered to be in the town’s drinking water. Town members were both stunned and dismayed to learn that NDMA exposure in utero was associated with an increased risk of childhood cancer, though the presence of other chemicals in the drinking water may have contributed. At the same time, town members felt vindicated having struggled for decades for both cleanup and answers. And at MIT, researchers became even more highly motivated to solve problems related to NDMA exposure. In fact, the team hopes to expand its work not only on NDMA but on related N-nitrosamines that have also been found at Superfund sites. While significant funding is being lined up for cleanup, key decisions with regard to how much cleanup should be done are pending. The MIT team aims to learn more about the biology of NDMA and related N-nitrosamines so as to contribute to informed decisions about the extent to which cleanup should be performed. In addition, MIT biological engineers aim to develop biomarkers that predict the downstream health consequences of NDMA long before disease onset. This is particularly important given that exposure to NDMA takes years to show up as cancer. The MIT team has also recruited new members who have expertise in water remediation. By bringing together a cross disciplinary team the MIT SRP has the potential to make a significant impact on public health by helping to protect people from hazardous chemicals.
