Chemical promotes cancer development in fish The experiments were fishy. But they appear to have uncovered something that rodent studies missed: a potential cancer risk posed by a compound used to manufacture nonstick coatings.

By mimicking the action of estrogen, this chemical, perfluorooctanoic acid, can promote cancer development, researchers report in an upcoming Environmental Health Perspectives.

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Better known as PFOA, perfluorooctanoic acid is the nonstick agent that DuPont developed and used to launch its Teflon line of products more than 50 years ago. PFOA-based nonstick chemicals now appear in everything from carpets and fry pans to microwave popcorn bags.

Studies performed in the early 1990s showed that PFOA could induce liver tumors in rats. The mechanism by which it did this, though - a proliferation of subcellular features known as peroxisomes - isn't applicable in humans. This led many toxicologists to generally close the book on PFOA as a potential carcinogen.

"But our data indicate the book is not closed," says Abby D. Benninghoff of Oregon State University in Corvallis. Working with juvenile rainbow trout, her team has just shown that in animals given a carcinogen, PFOA can double the cancer incidence. Treating carcinogen-exposed fish with estrogen does the same thing.

Additional tests further linked PFOA's estrogenic alter ego to its cancer-fostering role.

The new paper "shows that PFOA can promote liver tumors in a fish model that has been used as a human model for two decades," says John A. McLachlan, director of the Tulane/Xavier Center for Bioenvironmental Research in New Orleans.

Some liver cancers in people have also been linked to estrogen-like drugs. McLachlan points out that three years ago the International Agency for Research on Cancer linked liver-cancer risk to such estrogenic agents as birth control pills and post-menopausal synthetic estrogens.

In humans, estrogens have been linked most strongly with risk of reproductive-system tumors. Rodent studies have linked PFOA with tumors in those tissues as well, notes Kristina Thayer of the National Institute of Environmental Health Sciences, in Research Triangle Park, N.C. Considering the spectrum of tumors associated with PFOA in rodents, she says some scientists suspected that one mechanism couldn't explain it all. The Oregon State study now "helps confirm that there's more going on than just peroxisome proliferation."

Benninghoff's team worked with trout because "like humans, they don't respond to chemicals that cause peroxisome proliferation." The researchers exposed 10-week-old fish to aflatoxin, a fungal poison, for 30 minutes. Some fish were then exposed chronically for the next 30 weeks to PFOA at any of several doses.

Between 10 and 30 percent of the fish exposed only to the aflatoxin eventually developed a liver tumor or two. In contrast, 60 to 70 percent of the animals that also got high doses of PFOA developed liver cancer. PFOA-treated fish sometimes ended up with six or more tumors. Meanwhile, PFOA caused no tumors in the absence of pretreatment with aflatoxin.

Eight major companies make PFOA. Concerned by the emerging evidence of the chemical's toxicity, the Environmental Protection Agency got those manufacturers to agree two years ago to phase down their production of PFOA and related compounds by 95 percent by 2010.