Data from epigenetic research can be incorporated into the risk assessment process and used to inform regulatory decisions, according to Rebecca Fry, Ph.D., from the University of North Carolina at Chapel Hill (UNC). Fry presented her research on inorganic arsenic as a case study during the May 4 U.S. Environmental Protection Agency (EPA) Cutting Edge Speaker Series in Research Triangle Park (RTP).
“Arsenic is a high priority for the agency, as well as for the larger scientific community,” said John Vandenberg, Ph.D., director of the EPA National Center for Environmental Assessment, RTP Division. “Dr. Fry’s research goes from a molecular level all the way up to the population and community level, which is unique. Her work is incredibly insightful and important, particularly since we are currently working on the risk assessment of inorganic arsenic.”
Fry directs the UNC Superfund Research Program (SRP) Center(https://tools.niehs.nih.gov/srp/programs/Program_detail.cfm?Project_ID=P42ES005948) and has been exploring the health impacts of metals for almost two decades.
Focus on critical early life exposures
Using data from a group of pregnant women exposed to arsenic in drinking water in Gomez Palacio, Mexico, Fry and her team are studying how early life exposure to arsenic is related to adverse health outcomes.
“Studies in animals and human populations have shown that early life exposure to arsenic, such as in utero or early childhood, is associated with an increased risk of infants being born at lower birthweight,” noted Fry. “Of concern, these early life exposures are also associated with increased mortality and risk of disease later in life.”
Although they have found that infant birthweight decreases with increasing arsenic exposure, Fry is also interested in identifying the key molecular events that trigger such outcomes. “Arsenic can act through several molecular mechanisms to cause disease, but it is unknown which of these mechanisms is the most important for the adverse outcome or what the precise biological chain of events is,” she said.
Epigenetic changes as key molecular events
According to Fry, epigenetic modifications, which alter the way genetic information and proteins are expressed without directly changing DNA, may represent important biological mechanisms underlying disease. For example, her team found that DNA methylation, which serves as a molecular switch to turn genes on or off, increased with arsenic exposure across the population.
Fry’s lab identified one imprinted gene, called KCNQ1, that illustrated this trend. It is heavily involved in fetal growth, size, and weight. “One very interesting feature of imprinted genes is that their methylation likely occurs in the DNA of the parent’s reproductive cells prior to conception,” Fry said. “This points to preconception as a potential additional critical window of exposure, from an intervention standpoint.”
Epigenetic research used for risk assessment
Epigenetic changes could potentially be used as biological markers to indicate exposure to certain toxicants or to indicate early signs of disease, Fry said. Epigenetic data can also be incorporated into benchmark dose modeling, which would allow researchers to estimate the lowest exposure level associated with methylation of the target gene.
“Incorporating epigenetic research into the risk assessment process will help scientists and decision makers identify molecular mechanisms underlying disease, and estimate exposure concentrations that are associated with adverse health outcomes in the population,” she emphasized.
(Adeline Lopez is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)