Environmental Factor

July 2011


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Superfund postdoc unravels arsenic exposure

By Melissa Kerr
July 2011

Courtney Kozul-Horvath, Ph.D.

Kozul-Horvath discussed her findings in a presentation titled "Developmental and Immunological Effects of Low Dose Arsenic Exposure in Mice." (Photo courtesy of Jennifer Weinberg)

Mary Gant

Bethesda, Md.-based NIEHS Legislative Liaison Mary Gant happened to be on campus and made a point of attending the talk. (Photo courtesy of Jennifer Weinberg)

Linda Birnbaum, Ph.D.

NIEHS/NTP Director Linda Birnbaum, Ph.D., doesn't get to as many talks as she'd like, but she wasn't about miss this one on arsenic and windows of susceptibility. Birnbaum had several questions for Kozul-Horvath about her future plans. (Photo courtesy of Jennifer Weinberg)

Arsenic exposure does not have to be in large doses in order to have severe damaging effects on a biological system, according to Courtney Kozul-Horvath, Ph.D.(http://www.dartmouth.edu/~toxmetal/about/research-team/faculty/courtney.html) Exit NIEHS, a Superfund Research Program trainee at Dartmouth Medical School who discussed her research June 17 at NIEHS. Kozul-Horvath became intrigued with the effects of environmental exposure to low doses of arsenic during her graduate work at Dartmouth, and she continues to investigate the threat of exposure to this dangerous metalloid on public health worldwide.

Arsenic in the United States

Arsenic is a naturally occurring element and can also enter drinking water as a by-product of agricultural and industrial activities. Human exposure to arsenic has resulted in a variety of health effects that include cancer of the lungs, skin, and liver. Kozul-Horvath cited a 2006 article(http://ehp03.niehs.nih.gov/article/info:doi%2F10.1289%2Fehp.114-a486a) published in Environmental Health Perspectives that described arsenic as the "liquid path to lung disease."

Because of the health effects caused by arsenic, in January 2006 the Environmental Protection Agency (EPA) lowered the acceptable level of arsenic in drinking water from 50 parts per billion (ppb) to 10 ppb.

Kozul-Horvath works in New Hampshire, which is also known as the "Arsenic State," and one of her earlier projects was an education video for people who rely on well water in parts of New England where arsenic levels are a threat to their health.

Download Media Player: Flash external sites  (http://get.adobe.com/flashplayer/)

"This is a problem because as much as 50 percent of the population in New Hampshire and Maine get their water from private wells, which are not regulated," she explained. Within this region, the typical level of arsenic found in private wells ranges from 1 to 100 ppb.

Arsenic in the lungs

"One of the hypotheses that I have been beating around for the last four years or so is that perhaps arsenic is able to elicit such a variety of different health effects, because maybe it affects the immune system," Kozul-Horvath said.

Kozul-Horvath's research team set up a study where two sets of mice were infected with a mouse-specific strain of H1N1 influenza virus. The mice were divided into two groups. One group was infected only with H1N1. The other group was exposed to 100 ppb of arsenic in their drinking water and then infected with H1N1.

The researchers found that the arsenic-exposed mice, although they were exposed to the same level of flu, had about 10-fold more of the virus in their lungs. Early in the infection, arsenic-exposed mice had no immune response to major infection of virus. Later in the infection, there is an overabundant response that leads to hemorrhaging within the lung.

"This tells us that these [CD8] cells in the arsenic-exposed mice are not functioning to clear the virus properly," Kozul-Horvath explained.

Arsenic exposure during early development

In the next phase of experiments, Kozul-Horvath and her team were interested in attempting to discern roles of arsenic exposure on the development of the immune response. This time using the EPA standard of 10 ppb, the research team used four mice groups: mice that have never been given arsenic, mice that are only exposed to arsenic during the postnatal period, mice that only experience arsenic exposure during the in utero period, and mice receiving arsenic during their entire developmental period. The results showed that the growth rate of the mice was significantly affected, regardless of when they were exposed, with females more affected than males.

Kozul-Horvath looks forward to continuing to determine the roles that low-levels of arsenic play in the development of the immune system. She would also like to explore further how arsenic exposure changes the immune system response to an infection of influenza.

"We keep lowering and lowering our dose, figuring that eventually we are going to bottom out and not see an effect, but we're just surprised one time after another by the types of things that we see in this model," she concluded.

(Melissa Kerr studies chemistry at North Carolina Central University. She is currently an intern in the NIEHS Office of Communications and Public Liaison.)

Bill Suk, Ph.D. and Courtney Kozul-Horvath, Ph.D.

Kozul-Horvath joined the host of her lecture, SRP Director Bill Suk, Ph.D., left, on the patio outside the NIEHS main building. (Photo courtesy of Jennifer Weinberg)

Heather Henry, Ph.D.

NIEHS Health Scientist Administrator Heather Henry, Ph.D., joined several other members of the SRP at the presentation. (Photo courtesy of Jennifer Weinberg)

Mike Waalkes, Ph.D.

NIEHS Principal Investigator Mike Waalkes, Ph.D., was literally on the edge of his seat as Kozul-Horvath described her data. Waalkes, who heads the NTP Inorganic Carcinogenesis Branch, is the author of what has been described as one of the three most important recent papers about arsenic. (Photo courtesy of Jennifer Weinberg)

An impressive list of honors and awards

Although Kozul-Horvath is still a young scientist, she has already been the recipient of several awards and commendations. The list includes awards from the Women in Toxicology Scholarship Fund, the Northeast Society of Toxicology, Molecular Biology Specialty Section, "Best Student Poster" at the Superfund Research Program's annual meetings in 2007 and 2008, various awards from the Society of Toxicology, and the "Outstanding Oral Presentation" award from the International Central and Eastern European Conference on Health and the Environment in 2008.

Just this past year, she was the recipient of NIEHS's annual award presented in honor of Karen Wetterhahn, Ph.D. (see story(http://www.niehs.nih.gov/news/newsletter/2010/december/spotlight-dartmouth.cfm)). Wetterhahn was a leader in heavy metals research who died in 1997 as a result of a lab accident. Kozul-Horvath exemplifies the qualities of scientific excellence the Wetterhahn award was designed to honor.

She is also a Ruth Kirschstein National Research Service Award fellowship awardee.



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