Tuesday, September 6, 2011

Orarat Wangpradit, who earned a Ph.D. in human toxicology in 2011, researches toxic chemicals called PCBs (polychlorinated biphenyls). Once widely used in a wide range of applications, from paints to sealants and coolants, PCBs were banned in the United States in 1979.

Still, PCB contamination remains in our environment. Because PCBs are oil soluble, toxic levels of these chemicals can be found in fish and shellfish caught in areas such as the Great Lakes. Other instances of food source contamination have been documented, including problems with chicken, eggs, and pork. Exposure can also occur through inhaling PCB contaminated air or through skin contact with old electrical equipment. PCBs have been implicated in or related to cancer such as malignant melanoma, breast, and lung cancers in exposed populations.

Human toxicologists like Wangpradit and Garry Buettner, professor of radiation oncology and faculty member in human toxicology, research the details of interaction between such toxic chemicals and human cells. In the process, this team has studied disruptions that occur at a molecular level and can cause cells to develop mutations in their DNA.

These studies have led Wangpradit and Buettner to details about how human cells metabolize, or break down, PCBs. Normally, cells metabolize substances to derive and use life-sustaining components in those substances. This is how our bodies treat the substances we take in as food, transforming them into building blocks and fuel.

But when the substance is toxic, the game changes.

As Wangpradit and Buettner studied the ways in which human cells break down PCBs, they knew they needed to focus on the byproducts of that metabolic process – metabolites. Many PCB metabolites have been identified over the years, but Wangpradit and Buettner examined two types in particular.

Semiquinone and quinone free radicals are formed through metabolic processes of oxidizing PCBs. Semiquinones are the result of oxidation that removes one electron from the PCB-metabolite; quinones form when oxidation removes two electrons.

While the wider PCB research community has focused more on semiquinones, the University of Iowa researchers made a surprising discovery. They found that only quinones, not semiquinones, react with proteins and DNA to form a powerful bond that may lead to errors in DNA replication (mutation).

With two electrons missing, the quinones can form a covalent bond – a very strong bond that results from the sharing of one or more pairs of electrons.

“If these types of bonds are formed in cells, what does that mean? If these molecules make a bond with your enzymes or directly with DNA, new harmful chemistry can occur that can put an error into DNA that may result in mutations,” Buettner said.

Mutations in a cell’s DNA can lead to health concerns, including cancer, problems with immune function, and hormone disruption – all issues that have been associated with human exposure to PCBs.

“This is highly relevant to metabolism, to cancer research, and to other areas,” said Larry Robertson, professor of occupational and environmental health, director of the human toxicology program and Wangpradit’s mentor. “This is going to be fundamental and basic to our understanding of the chemistry and toxicology of foreign chemicals and how they are metabolically activated.”

For Wangpradit, this discovery was an exciting way to conclude her graduate college career at the UI.

Wangpradit came to the UI from Thailand on a Royal Thai Government Scholarship.

Royal Thai Scholarships provide full educational and living costs for an initial award of two years for a master’s program or four years for a doctoral program; extensions of one or two additional years are possible for students making good progress towards completion of a degree. The scholarship recipients are obligated to work for their government agency for twice the time they were supported.

Wangpradit also earned a master’s degree at the UI in occupational and environmental health in 2007. She is now teaching at Sirindhorn College of Public Health in Thailand.

Wangpradit would recommend attending the University of Iowa to other Thai students.

“It was really beneficial for me,” Wangpradit said. “Dr. Robertson is the PCB expert. For me, it was wonderful to have a broad array of experts with whom you can consult and get advice on your research.”

Buettner credits Wangpradit for playing a major role in this latest discovery. “She’s an idea generator who translated ideas into doable experiments,” Buettner said.