Researchers at Oregon State University have pioneered a method that allows them to track tiny amounts of a possible carcinogen in humans, work they hope will give them insight into how the body deals with these compounds.
At issue are compounds called polycyclic aromatic hydrocarbons, PAHs for short. These substances are the product of the incomplete combustion of carbon, and we run across them routinely as part of our daily lives – in auto exhaust, for example, but also in foods such as smoked meats.
“They’re found in vegetables, fruits, cereals, dairy products,” said David Williams, who directs the Superfund Research Program at OSU and also serves as a professor in the College of Agricultural Sciences and with the Linus Pauling Institute. “They’re pretty much ubiquitous.”
They’re also the subject of increasing concern in the scientific world – PAHs or PAH mixtures have been named as three of the top 10 chemicals of concern by the Agency of Toxic Substances Disease Registry.
Williams and Erin Madeen, a doctoral student at OSU, along with other collaborators at Oregon State University and the Pacific Northwest National Laboratory developed analytic methods for PAH research. The accelerator mass spectrometry capacity at the Lawrence Livermore National Laboratory in California is used to examine blood samples taken from test subjects who have ingested a small amount of a PAH – in one case, dibenzo (def,p)-chrysene.
The amount of the PAH ingested in capsule form is about the same amount that someone would eat in a 5-ounce serving of smoked meat.
The accelerator mass spectrometer at Livermore then is able to look in exquisite detail at the blood samples, which are taken at timed intervals from the subjects, and is able to track even the tiniest amounts of the PAHs as the body deals with them.
Madeen helped design the protocols for the experimental work. She said the proposal initially raised eyebrows in that it involved giving tiny amounts of a suspected carcinogen to human subjects.
“But there should be a context for everything,” she said. “This is the level of PAHs that an average person does consume in their diet every day. So this is no extra burden than what a person would already have had in their diet.” Experts who reviewed the experiment determined that it adds no additional risk to its subjects, she said.
Williams has been researching PAHs for more than three decades. He got the idea to enlist the high-tech equipment at Livermore after visiting the lab as part of an unrelated trip to assess research proposals for the National Institutes of Health.
“It just blew me away,” he said. “When I saw the power of that, I said, ‘I’ve really got to do this someday and work this into my research program.’”
The opportunity to do that came after OSU won grants as part of the Superfund Research Program at the National Institute of Environmental Health Sciences. That work isn’t involved as much with the cleanup of Superfund sites as it is in determining the effects of exposure to the chemicals found at Superfund sites.
And using the accelerator mass spectrometry capacity at Livermore adds an exciting new dimension to that work.
“Up until now, people in risk assessment … have had to rely on really high-dose animal models,” Williams said. “If you look at the dose we give a person, it’s about 100 million times less than the dose you’d have to give a mouse. That’s the power of this instrument and this approach.”
Added Madeen: “That’s pretty exciting because this is at a realistic dose. This is actually what happens on a daily basis in any given person.”
Early results from the recent OSU tests tend to confirm a general truth about PAHs — that our bodies are actually fairly efficient at metabolizing them. But, as Madeen noted, metabolism can be a two-edged sword: Some of the results suggest that the metabolism clears the way for the compound to be excreted from the body — but, along that path, the compound also is capable of finding and binding with DNA.
And Williams and Madeen already are recruiting volunteers for follow-up studies, all of it made possible by a powerful procedure that lets them peer more closely into the workings of the body than ever before.