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Your Environment. Your Health.

December 2018 Superfund Research Program Science Digest

Superfund Research Program Science Digest
Balancing Scientific Excellence with Research Relevance


Nutrition and Environmental Health

Basket full of produce

Superfund Research Program (SRP) scientists and engineers are using a variety of methods to explore the role of nutrition in protecting against chemical toxicity and associated diseases. Their work is providing unique insights regarding interventions that reduce the burden of disease associated with exposure to hazardous substances and improve human health.

Folate Interventions to Address Arsenic Exposure

In 2000, researchers at the Columbia University SRP Center established a large prospective cohort study in Bangladesh called the Health Effects of Arsenic Longitudinal Study (HEALS). Led by former Center Director Joseph Graziano, Ph.D., and Habibul Ahsan, M.D., HEALS data has directly linked arsenic exposure to a variety of negative health outcomes, including skin lesions, cardiovascular disease, and impaired lung function.

Building off extensive work in the HEALS cohort, Mary Gamble, Ph.D., has explored the role of nutrition, specifically folate, in arsenic metabolism and detoxification. Her team previously found that folate influences arsenic methylation and went on to report that folate deficiency is a risk factor for arsenic-induced skin lesions. They also found that folate nutritional status may explain some of the differences in arsenic metabolism between individuals and, therefore, their susceptibility to arsenic toxicity.

Gamble has conducted randomized clinical trials, which demonstrate that folate supplementation facilitates arsenic methylation and lowers blood arsenic, while possibly reducing arsenic's toxic effects, thus pointing toward an alternative intervention strategy.

Fruits and Vegetables to Counter Health Effects of PCBs

Handful of blackberries

Blackberries, the state fruit of Kentucky, are rich in healthy polyphenols.
(Photo courtesy of the University of Kentucky SRP Center)

Researchers led by Bernhard Hennig, Ph.D., at the University of Kentucky (UK) SRP Center have examined the impacts of dietary components on cellular responses to polychlorinated biphenyl (PCB) exposure. Their work has identified a link between exposure to PCBs, diet, and cardiovascular disease.

They discovered that certain nutrients called polyphenols, found in fruits, vegetables, and spices, can protect against the harmful effects of PCB exposure. Specifically, they reported that polyphenols protect cells from damage, such as oxidative stress and inflammation, associated with PCBs. They further discovered that diets rich in polyphenols can reduce the risk for PCB-associated type 2 diabetes in humans.

Based on this research, the UK SRP Center has been working to reduce the harmful effects of PCB exposure by educating the community and conducting nutritional interventions. The Center’s Community Engagement Core has offered cooking classes that teach healthy behaviors, as well as how to prepare fruits and vegetables and incorporate them into healthy meals.

How Diet Interacts with Toxins to Harm Health

While nutrition has been shown to play an important protective role in toxicant-induced disease, some researchers have discovered that components of unhealthy diets can worsen the health impacts of hazardous substances.

Michael Karin, Ph.D., from the University of California, San Diego (UCSD) SRP Center has explored the role of nutrition, specifically high-fat diet, in liver cancer in mice. His work has identified that a high-fat diet triggers an inflammatory response and elevates the production of cytokines, such as TNF and IL-6 important for cell signaling, which lead to hepatocellular carcinoma (HCC).

Karin’s team also has demonstrated that endoplasmic reticulum stress combined with a high-fat diet results in HCC. Their mechanistic research has helped identify anti-TNF therapy as a potential target to treat liver disease and prevent tumor progression.

Hennig’s team also has made important discoveries about the role of unhealthy fats in worsening the harmful effects of PCB exposure. For example, Hennig’s laboratory demonstrated that the type of fat in the diet, not just the amount of fat, can make a difference in cell damage triggered by environmental chemicals. They found that an omega 6 fatty acid called linoleic acid can increase PCB-induced endothelial dysfunction, an underlying step in the development of heart disease.

Identifying Dietary Sources of Contaminants and Informing Health Protections


The chemical structure of arsenic resembles important plant nutrients, causing it to be taken up into the plant.
(Photo courtesy of the Dartmouth SRP Center)

The Dartmouth SRP Center has been investigating rice as an important human exposure route for arsenic. In 2012, researchers led by Brian Jackson, Ph.D., used advanced techniques to measure arsenic concentrations in several rice-based products. The study resulted in breakthrough information on high levels of arsenic in brown rice syrup, a substitute for corn syrup in many foods, including toddler formula.

This discovery informed the Food and Drug Administration’s Inorganic Arsenic in Rice Cereals for Infants: Action Level Draft Guidance for Industry and contributed to a science synthesis project, the Collaborative on Food with Arsenic and associated Risk and Regulation, published in Science of the Total Environment. It also has informed a Government Accountability Office examination of federal policies pertaining to arsenic in food.

Based on Center findings, the Dartmouth SRP Research Translation Core developed Arsenic and You, a website providing comprehensive information on arsenic in food, water, and other sources.

A recent commentary from Dartmouth, Opportunities and Challenges for Dietary Arsenic Intervention, introduces a framework for interventions at all stages of the food supply chain, from field to plate. This model can be used to identify monitoring, intervention, and communication opportunities to mitigate dietary arsenic exposure. For example, researchers led by Mary Lou Guerinot, Ph.D., have been working to understand arsenic uptake, transport, and storage in rice plants. As part of this work, they are determining which genes help the plant keep arsenic from entering through the root system. This represents an intervention opportunity at the first step of the food supply chain during food growing and production.

Finally, led by Julian Schroeder, Ph.D., UCSD SRP researchers have explored the molecular mechanisms by which plants accumulate metals. This may offer opportunities for limiting toxic metal and arsenic accumulation in edible plant tissues.

Measuring and Reducing Contaminants in Garden Produce

Researchers at the University of Arizona (UA) SRP Center are working to understand how people are exposed to arsenic in mine wastes and the potential health impacts of those exposures. For example, they characterized arsenic uptake in homegrown vegetables in mining-affected soils, including which vegetables accumulated the most arsenic.

Led by Mónica Ramírez-Andreotta, Ph.D., the UA SRP Center’s Research Translation Core worked with residents of Dewey-Humboldt, Arizona to investigate the uptake of arsenic in commonly grown vegetables and to evaluate arsenic exposure and potential risk to local vegetable gardeners. As part of their citizen science research project, called Gardenroots, they found that the main sources of arsenic exposure were drinking water and incidental soil ingestion. They also learned that arsenic concentrations were higher in homegrown vegetables than store-brought produce.

The researchers reported the study results back to the community and provided more information on how to interpret those results. The team also provided handouts outlining recommended safe gardening practices to help reduce one’s arsenic exposure.

A group of people standing in a garden

Community members, UCSD researchers, and SRP staff at the OVGG.
(Photo courtesy of Keith Pezzoli)

Led by Keith Pezzoli, Ph.D., the UCSD SRP Center’s Community Engagement Core works to address concerns about toxicants in soil, water, and plants through urban agriculture. They have been working to transform a 20,000 square foot vacant lot into the Ocean View Growing Grounds (OVGG), which includes a community garden, food forest, and neighborhood-based environmental research and learning center.

Because the OVGG is on a brownfields site, the team tested fruits and vegetables grown there to make sure they were safe to eat. They analyzed plant tissues to monitor whether metals accumulated in the plants over time.

Through the OVGG project, the team is working to address the combined effects of poverty, obesity, environmental pollution and degradation, and lack of access to fresh fruits and vegetables. This solutions-oriented approach to environmental health concerns offers the community a unique place to grow nutritious food and to learn about urban agriculture and healthy eating.

Addressing Tribal Community Concerns

Artwork illustrating DNA damage and repair

The UNM METALS Center uses Native American art and symbolism to communicate their scientific research. The artwork above illustrates how uranium damages DNA (left) and how zinc can repair DNA damage (center) to protect immune cells and function (right).
(Photo courtesy of the UNM SRP Center)

The University of New Mexico (UNM) Metals Exposure and Toxicity Assessment on Tribal Lands in the Southwest (METALS) SRP Center focuses on risk reduction for Native Americans exposed to hazardous metal mixtures from abandoned uranium mine waste. In addition to understanding how metals move through the environment and impact human health, the team is exploring zinc supplementation as a strategy to lessen the harmful effects of metal exposures on the immune system. The UNM SRP Center team, led by the Community Engagement and Research Translation Cores, have worked to communicate findings using Native American art and symbolism.

The Brown University SRP Center’s Community Engagement Core has been working to address the concerns of Native American communities about contaminated fish in tribal waters. Led by Marcella Thompson, Ph.D., the team has been working to assess the impacts of environmental contamination on the Narragansett Tribe and to facilitate informed decision making regarding contaminated fish in tribal waters and fish consumption among tribal leaders and members. The team is exploring a complex relationship between food, culture, and toxicants in the environment through their Namaus Project, which translates to “all things fish” in the Narragansett language.

A shed, a tipi, and salmon

OSU researchers compared shed and tipi smoking structures (A, D) and salmon placement (B, E) used for traditional salmon smoking to evaluate exposure to PAHs.
(Photo courtesy of Forsberg et al. 2013. Effect of Native American fish smoking methods on dietary exposure to polycyclic aromatic hydrocarbons and possible risks to human health. J Agric Food Chem. 60(27):6899-6906.)

Researchers at the Oregon State University (OSU) SRP Center have collaborated with two northwestern tribes, the Swinomish and the Samish, to analyze important cultural foods for contaminants like polycyclic aromatic hydrocarbons (PAHs). The team has used several approaches to understand the effect of traditional Native American fish smoking methods on dietary exposure to PAHs and has developed an approach for sharing research data with tribal communities. They found that while different smoking approaches did not influence PAH concentrations in fish, traditionally smoked salmon were 40 - 430 times higher in PAHs than commercial products, posing an elevated cancer risk for this population.

In response to tribal concerns about contaminants in butter clams, the OSU SRP Center team collected clams for analysis and deployed passive pore-water samplers in the sediment. To preserve important cultural resources, the team is also developing a method to predict the concentration of PAHs in foods like crayfish and butter clams without sampling them directly.