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School of Public Health and Community Medicine - University of Washington - Summer 2006
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Toxicology In Action
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Student Research Day
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A Basis For Counseling | Explaining Health Effects

TOXICOLOGY IN ACTION

Our department's Toxicology program involves research ranging from basic to applied sciences. The following two stories about graduate student research explain some of the ways toxicological studies inform us about human health. The remainder of this issue summarizes the highlights of our 2005-2006 school year, including degrees, awards, and presentations at spring conferences.


A Basis For Counseling

A small snip of hair rarely changes anyone's life. But for Ami Tsuchiya, it revealed a level of mercury in her body so surprising that it spurred her toward a new course of study.

Ami Tsuchiya picture
Ami Tsuchiya takes a hair sample from a study participant for mercury analysis.
Photo by Alison Scherer.

While pursuing her master of public health degree in nutrition at the University of Washington in 2002, Tsuchiya took part in an environmental health class project focused on mercury exposure through fish consumption. Separately, she had an opportunity to have her hair tested.

"That project was really intriguing because, having a nutrition background, I thought fish was really good for you," she said. "And then I saw my mercury level. So I thought maybe I should really study this."

She entered the master's program in Toxicology and, this summer, will wrap up a study of mercury exposure among local Japanese women. For her thesis, Tsuchiya recruited Japanese women of childbearing age through a Kirkland clinic, run by nurse practitioner-midwife Sachiko Oshio. Tsuchiya estimated their methylmercury exposure based on reported fish consumption habits, mercury analysis of fish purchased locally, and biological samples of hair, blood, and toenails.

Professor Thomas Burbacher, Tsuchiya's advisor, introduced her to Washington State Department of Health (DOH) toxicologist Koenraad Mariën , who has a grant to study the topic. Tsuchiya's thesis work is part of a larger DOH study led by Mariën .

"The objective of this study is to determine if certain individuals or subpopulations within the Japanese and Korean communities may be overexposed to methylmercury obtained through the consumption of finfish and shellfish from Puget Sound as well as from other sources," Mariën said.

A 2003 study led by Clinical Assistant Professor Ruth Sechena revealed that Asian American and Pacific Islanders (AAPI) in King County consume, on average, more seafood than the general population. While the study included only small sample sizes, it raised the concern that AAPI seafood consumption practices may put this population at greater risk of mercury exposure.

Because the methylated form of mercury can move from the blood into the growing hair shaft, Tsuchiya's hair tests can indicate the level of methylmercury in the body. High body burdens of methylmercury have been associated with debilitating diseases of the nervous system. If pregnant women are exposed to too much methylmercury, it can result in birth defects in their children.

Study Interviews

At the Kirkland clinic, Tsuchiya visits with each participant three times during the study period. During the first visit, she asks them about their fish consumption habits using fish models she brought back from Japan to identify portion size and species. Next, she weighs participants and asks for their pregnancy status.

"Then I cut their hair, about the width of a pencil, from the nape of the neck," Tsuchiya said. "I wrap it in paper and send it to the lab." The nurse-midwife may also draw blood. After participants complete a self-administered food frequency questionnaire, Tsuchiya counsels them about their fish intake with the aid of a brochure published by DOH.

"I explain which fish are low in mercury, and which fish are high in mercury, especially shark, tile fish, tuna steak, king mackerel, and swordfish." Half of the brochure is dedicated to advice about canned tuna consumption. "But for our population, canned tuna isn't the problem...at the end of the study, we hope to make culturally appropriate brochures." At the second visit, Tsuchiya reviews the women's mercury test results. At the third visit, she follows up and collects more samples, and counsels the women.

Tsuchiya told one of her participants: "Your results show you are eating fish, which is good. You're at a [mercury] level where birth defects are not seen. Just keep doing what you're doing." She emphasized that fish is a low-fat, protein-rich food that belongs in a healthy, well-balanced diet. As with the other interviews, she offers to set up an appointment with Mariën if there are questions she can't answer or with a healthcare practitioner if results indicate high mercury exposure.

Family of Researchers

At this year's Student Research Day, Graduate Program Coordinator Matt Keifer introduced Tsuchiya. Keifer noted that he first met her a decade ago when she visited the campus with her late grandfather, Dr. Kenzaburo Tsuchiya, a prominent Japanese researcher who investigated the link between a painful bone-weakening disease known as itai-itai (literally "ouch-ouch") and cadmium contamination. "It's an honor to have his granddaughter at our school and presenting today," Keifer said (Mercury Exposure & Fish).

Mariën said Tsuchiya has been an ideal researcher for his study. "We are fortunate to have her working with us," he said. "Her bilingual skills, her knowledge of the Asian communities, as well as her master's degree in nutrition, have been of immense benefit during this endeavor."

Tsuchiya has enjoyed meeting so many people and offering them advice. "I want to do nutritional counseling and I think I'm most effective one-on-one," she said.

-Alison Scherer

For Futher Reading

DOH: Fish Facts for Healthy Nutrition:
http://www.doh.wa.gov/fish/default.htm

Sechena R, Nakano C, et al. 1999. Asian and Pacific Islander seafood consumption study. Available from http://www.epa.gov/r10earthoffices/oea/risk/a&pi.pdf

Mariën K, Patrick GM. 2001. Exposure analysis of five fish-consuming populations for overexposure to methylmercury. J Expo Anal Environ Epidemiol 11(3):193-206

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EXPLAINING HEALTH EFFECTS

In a specially designed research laboratory near campus, mice inhale carefully diluted and aged diesel exhaust intended to mimic urban air pollution. If you've ever spent time waiting for the bus in the U-District, you might know how these mice feel.

Epidemiological research shows that when ambient particulate air pollution levels rise, so do instances of cardiovascular effects and death. Diesel exhaust, the largest contributor to urban ambient air pollution, plays center stage in a University of Washington study of cardiovascular effects. The results might shed light on ways to minimize human health effects in the future.

Ami Tsuchiya picture
Lisa Corey in the lab.
Photo by Alison Scherer.

"It would be nice to figure out why there are cardiovascular changes involved with increases in particulate matter, because at that point we could potentially stop them," said researcher Lisa Corey. Corey, who received her master's degree in Toxicology here, is two years into the Toxicology PhD program. She began participating in this research project autumn quarter.

The mice, which lack a gene known as Apolipoprotein E, are used as a model of cardiovascular disease because they form advanced atherosclerotic plaques similar to those of humans, she said. Apolipoprotein E is a carrier for cholesterol in the blood, said Professor Dan Luchtel, Corey's advisor. "If you don't have the ApoE molecule, cholesterol builds up in blood vessel walls, leading to atherosclerosis," he said. In the human population, there are three versions of this gene, and genotype is associated with a variety of health effects.

During study experiments, the so-called ApoE-/-mice are exposed to exhaust at the lab for as short as one day to as long as eight weeks. Exposure levels range from filtered air to 400 mg/m3, which Luchtel describes as "like standing right behind a bus tailpipe. That's a hefty dose." He said ambient exposures to humans are generally 2 to 15 mg/m3.

"We're trying to understand the pathophysiological mechanism of response," Luchtel said. To do so, the study aims to measure several endpoints, including pathological changes in plaque formation and plaque stability, and markers of inflammation in the blood and lungs.

"It's likely that there is a complex mechanism from exposure to adverse effects that involves inflammation, which we will measure in various ways," Corey said. When (particulate matter) enters the lungs, it activates cells that call upon other inflammatory cells by secreting cytokines. We can measure changes in cell counts and cytokine levels."

She said that small airborne particles might be able to enter the bloodstream from the lungs and migrate elsewhere in the body. "There are also studies in animals suggesting that the smallest particles can be taken up by olfactory nerves and go from the nose directly to the brain," she said.

Using surgically implanted radio transmitters, Corey also measures heart rate changes among mice exposed continuously for eight weeks to diesel exhaust. Although researchers are not clear why particulate air pollution affects heart rate, direct damage to the lungs or action on nerves to the brain might be responsible. "Decreases in (heart rate variability) are considered adverse because it means that your heart cannot adjust or adapt to the changes that you throw at it," Corey said. "For example, you would collapse and faint if you had to run up a flight of stairs if your heart rate didn't increase to get more oxygen to your brain and muscles." Preliminary results show the mice experience decreased heart rate variability with increasing duration of exposure.
-Alison Scherer

For Futher Reading

OSHA health and safety topic: Diesel exhaust http://www.osha.gov/SLTC/dieselexhaust/index.html

American Lung Association of Washington newsletter story on diesel bus emissions http://www.alaw.org/pdfs/breathing_newsletters/2003_march_17/diesel_paper_2003.pdf