OREGON STATE UNIVERSITY

New Mechanism Identified for Action of Possible Carcinogen

05/16/2008

CORVALLIS, Ore. – Toxicologists at Oregon State University have identified a new biological mechanism by which a possible carcinogen – a chemical compound that’s widely used in everything from food wrappings to stain-resistant clothing – might increase cancer risk.

The findings were just reported in Environmental Health Perspectives, and relate to perfluorooctanoic acid, or PFOA. Commonly used for decades in many industrial processes, PFOA tends to persist in the environment and can be easily found in the blood of humans or many other animals all over the world.

The EPA is studying concerns about its possible role in developmental toxicity, cancer and other issues. Although in 2006 an EPA science advisory board voted to approve a recommendation that PFOA should be considered a “likely carcinogen,” the agency has made no final conclusions about its safety.

The new OSU study, done at the Sinnhuber Aquatic Research Laboratory with rainbow trout, concluded that PFOA significantly increased the incidence of liver tumors in a manner similar to the natural hormone estrogen – a very different mechanism than the way it had been shown to cause cancer in rodents.

“Laboratory rodents make very good animal models for many cancer studies, but this may not be one of them,” said Abby Benninghoff, a toxicologist with the OSU Department of Environmental and Molecular Toxicology and the Linus Pauling Institute . “The response of rodents and humans to PFOA exposure is most likely not the same. We have reason to believe that trout, which have been used to study cancer for 40 years, may react to PFOA exposure much more like humans do, and therefore provide more useful results.”

In rodents, Benninghoff said, exposure to high levels of PFOA causes a proliferation of “peroxisomes,” which are a part of normal cells that are involved in fat metabolism. Too much activity in these peroxisomes can increase oxidative stress, produce DNA damage and ultimately lead to cancer, researchers believe.

However, this “peroxisome proliferation” is much less of an issue with humans – or trout – perhaps because both humans and trout have fewer receptors that turn on the process of peroxisome proliferation. Because of that, it has been difficult to extrapolate to humans the findings about PFOA that were made with rodents.

By using microarrays that were able to study hundreds of genes in rainbow trout, scientists at OSU were able to identify a different way in which PFOA might cause cancer – it appears to mimic the action of the natural hormone estrogen. The researchers called it a “novel mechanism of carcinogenicity” for this chemical that merits further study.

In humans, several cancers have been linked to estrogen levels, including breast, uterine and ovarian cancer. Some cancer drugs are effective by blocking estrogen. Trout, as well as humans, are very sensitive to tumor promotion by estrogenic compounds.

“This does not, in itself, show that PFOA is a human carcinogen,” Benninghoff said. “However, it gives us an alternative way to understand how it might have those effects, and will provide direction for future research.”

PFOA is a member of a class of perfluorinated compounds that are widely used in many consumer products, such as lubricants, textile coatings, food wrappings, flame retardants, and other applications. PFOA has unusual chemical stability and tends to be found widely in animals, water supplies, and other areas. Some perfluorinated chemicals have been voluntarily removed from the market by manufacturers, but others – including PFOA – are still widely used.