Researchers Aim to Develop Blood Test to Determine Exposure to Dioxin And Related Compounds

BUFFALO, N.Y. -- A University at Buffalo research team has received a $770,000 grant to develop and validate certain biological markers in animals and humans that could lead to a simple blood test to determine exposure to dioxin and related chemical contaminants.

The researchers also will investigate whether these sensitive molecular and biochemical responses can determine if certain individuals are susceptible to the biologic and toxic activity of dioxin and related compounds.

The grant from the National Institute of Environmental Health Sciences is part of a major national research effort to develop ways to assess subtle human health responses to environmental insults, said James Olson, Ph.D., UB associate professor of pharmacology and therapeutics and the study's principal investigator. Olson is also associate director of the UB Toxicology Research Center.

"Our aim is to develop methods that might be applied in the next century to determine if a particular environmental circumstance is a health concern," Olson said. "Our project will investigate biological markers in mature animals, as well as newborns, which are more susceptible to the toxic activity of dioxin."

Olson said researchers at the University of Wisconsin exposed pregnant rats to very low doses of dioxin and found that the male offspring, at puberty, showed a lowered sperm count and abnormal development of the reproductive system.

"An environmental exposure that would cause that response in a human population would be a major problem," Olson added.

To assess the action of dioxin-like compounds in the body, Olson's team will concentrate on the part of a cell called the Ah receptor. The Ah receptor is necessary to initiate the wide range of biologic and toxic responses associated with exposure to dioxin and like compounds, Olson said.

He noted that when these compounds bind to the receptor, they go through structural changes and bind to DNA, which in turn initiates production of specific proteins called CYP1A1 and CYP1A2.

Olson's team will measure the presence of Ah receptor and CYP1A1 and CYP1A2 in tissue from maternal and fetal rat liver, placenta and white blood cells following exposure to dioxin. The researchers will determine if the presence of these substances can be used as markers, or indicators, of exposure, effect or susceptibility to dioxin and related compounds from environmental sources.

"If levels of Ah receptor indicate susceptibility to dioxin-like compounds," Olson said, "we can eventually predict who might be susceptible to effects from exposure to these compounds and who might not."

One part of the four-year project will use blood samples from persons known to have been exposed to dioxin-like compounds as a result of eating fish taken from Lake Ontario, where levels of these contaminants are high. Olson said eating contaminated fish and wildlife represents one of the greatest non-occupational exposures to dioxin-like compounds.

Olson's team will study biomarkers in white blood cells from this population for evidence of exposure to dioxin and related compounds. This part of the study is being conducted in collaboration with John Vena, Ph.D., associate professor of social and preventive medicine at UB.

Vena and the UB Toxicology Research Center are investigating the relationship between the consumption of fish from Lake Ontario, human exposure to dioxin-like environmental contaminants, and reproductive and developmental outcomes in a population of New York State anglers.

Another part of the study involves collecting placental tissues from a hospital in Oswego, N.Y., and assessing them for evidence of exposure to dioxin and related compounds. This part will be conducted in collaboration with Helen Daly, Ph.D., of the State University College at Oswego.

Olson's team also will investigate estrogen and caffeine metabolism as potential indicators of dioxin exposure in humans.

Co-investigators on the project are Vena and Thomas A Gasiewicz, Ph.D., of the University of Rochester. Other members of the team are Daly, Joyce A. Goldstein and George W. Lucier from the National Institute of Environmental Health Studies, and Miguel Rodriguez-Bigas from Roswell Park Cancer Institute in Buffalo.