Using transgenic mice, Charles River scientists have traced a path that leads from inhaled styrene to cancer – a path that does not exist in humans.

Styrene, an organic compound used in the manufacture of latex and synthetic rubber, has long been suspected of having carcinogenic properties. Many research bodies have studied the issue, but no firm causal relationship has been found between styrene manufacturing and cancer in humans, despite the fact that the compound has been shown to cause cancer in mice.

Thanks to recently published research in the July online issue of Toxicological Sciences, part of this mystery may have been solved by a two year research project that was funded by the Styrene Information and Research Center (SIRC). SIRC represents styrene manufacturers and other interested industry groups. Using transgenic mice, researchers at CRL facilities in Maryland have traced a path that leads from inhaled styrene to cancer – a path that does not exist in humans.

“Certain cells in the lungs of mice contain high levels of an enzyme that exists in much lower levels in rat and human lungs,” said Dr. James T. Raymond, a CRL Senior Scientific Director and one of the study’s authors. “This enzyme breaks down styrene, and the resulting product damages and kills lung cells. Over time the lung keeps trying to heal the damage, but the constant damage/healing cycle can lead to cancer.”

Some of the mice used for the study were bred to express either the enzyme CYP2F2, which is common in mice, or the enzyme CYP2F1, which is the corresponding enzyme found in humans. Researchers found that mice who expressed the human enzyme , or the “humanized mice,” did not develop lung tumors, while those who expressed the mouse-typical enzyme CYP2F2 developed lung toxicity and tumors.

Although more research is always required, this study seems to explain the discrepancy between observed cancer in mice and the lack of corresponding cancer incidence among humans who work closely with styrene in manufacturing. It further illustrates that despite the enormous usefulness of laboratory mice in the sciences, it is important to remember that, in most cases, a human is not a mouse.