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Scientists Get Proof of Natural Anti-Cancer System

Reuters

Tuesday, March 13, 2001

By Will Dunham

WASHINGTON, Mar 13 (Reuters) - Researchers said on Monday they have confirmed the existence of a natural system used by the body to defend against the cancer-causing effects of toxic chemicals in food and the environment.

Scientists had long suspected that such a system existed, but researchers at Johns Hopkins University in Baltimore and Tsukuba University in Japan said they used tests involving genetically engineered mice to confirm it after 20 years of research.

The system appears to be a common one in many animals, the researchers said, adding that they were seeking ways to use the corresponding system in the human body to help protect people from cancer.

The body's protective system hinges on a sharp boost in protective enzymes--called phase II enzymes--that can dispose of toxic chemicals. The enzymes effectively neutralize toxins' ability to damage DNA and trigger cancer, the researchers said.

Scientists already knew that natural substances in plants, such as the sulforaphane in broccoli, as well as some synthetic chemicals, could tap into this system to provide a protective effect.

In two studies appearing in the Proceedings of the National Academy of Sciences, the researchers said they not only demonstrated the basic workings of the system in mice, but also found a "switch" that regulates it.

"We've gained long-awaited proof of a basic mechanism that can reduce the risk of cancer," Dr. Paul Talalay, a Johns Hopkins molecular pharmacologist who participated in the research, said in a statement.

He said that raising the levels of phase II enzymes can provide a "highly effective way" to guard against cancer.

"Our precise understanding of this system should make it fairly easy to design drugs that can fine-tune it," added Johns Hopkins researcher Thomas Kensler, a toxicologist who is overseeing early clinical trials of one such drug in China.

"We have evidence that we can increase the system's levels of protection in people and are planning long-term studies that would reveal any lowered incidence of cancer."

The researchers focused on strategies that cells use to control activity of the phase II enzymes. They knocked out the "switch"--a protein called Nrf2--in a bid to remove the protective system in genetically engineered mice.

The researchers exposed both the "switched-off" mice and normal mice to benzpyrene, a potent carcinogen found in cigarette smoke. They said both types of mice developed tumors, but the "switched-off" mice had many more.

In addition, scientists gave both the normal and the "switched-off" mice a drug called oltipraz, which is used for parasitic infections and has been shown to reduce cancer risk, along with the cigarette smoke carcinogen. The normal mice had their tumor number cut by half, but the other mice were tumor-ridden, even with the protective drug.



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Last updated: 14 March 2001