Superfund Research Program
NDMA and DNA Alkylation Repair in the Liver: Impact of Gene-Environment Interactions on Cellular Responses, Mutations and Cancer
Year: 2018 2017
DNA repair is increasingly appreciated as a risk factor for cancer caused by environmental contaminants. The major objective of the Massachusetts Institute of Technology (MIT) SRP NDMA and DNA Alkylation Repair in the Liver: Impact of Gene-Environment Interactions on Cellular Responses, Mutations and Cancer Project is to reveal the impact of DNA repair factors (Aag and Mgmt) on susceptibility to N-nitrosodimethylamine (NDMA), a contaminant found in Superfund sites that is carcinogenic in animals. Together, Aag and Mgmt are responsible for repair of over 90 percent of NDMA-induced DNA damage. Studies are underway to reveal the impact of Aag and Mgmt on NDMA-induced mutations using genetically engineered mice. In addition to studies that are underway in animal models, the researchers have also developed methods for studying DNA damage and cytotoxicity in cultured mammalian cells. In particular, they have created a novel high-throughput platform for quantitation of cell survival (Ngo et al., “Microcolony Size Distribution Assay Enables High-Throughput Cell Survival Quantitation.” Cell Reports). Cytotoxicity assays are fundamental to a broad range of disciplines in the life-sciences. The novel “MicroColonyChip” is currently being used for analysis of NDMA-induced cytotoxicity as part of a collaboration with the Systems Toxicology of Environmental Contaminants Project. Taken together, ongoing studies are fundamental to the understanding of what makes some people more prone to cancer than others, and will enable analysis of DNA damage and DNA repair capacity in people as modulator of increased cancer risk caused by environmental chemical contaminants. The work is relevant to the Olin Chemical Superfund site in Wilmington, Massachusetts, where water is contaminated with NDMA.