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APRIL 22, 1999

Do Environmental Pollutants Make Cancers More Aggressive? Unique Medical College Study Seeks Answers

If you have prostate cancer, could puffing a cigarette or breathing diesel fumes behind a bus make your cancer spread faster? That's a question Medical College of Wisconsin researchers, headed by Paul F. Lindholm, M.D., assistant professor of pathology, and Andre Balla, M.D., associate professor of pathology, are trying to answer. Their preliminary research suggests that aggressive prostate cancer cells are different from dormant cells, and that environmental pollutants (such as heavy metals, cigarette smoke, pesticides, or car and truck emissions) may cause slow-growing prostate cancers to become more aggressive. If they do, they may attack surrounding tissue, and spread more rapidly through the body.

Doctors have long known that some prostate cancer (cancer of the walnut-shaped gland that wraps around the urethra in males) grows very slowly and doesn't invade surrounding tissue, while other men's prostate cancers spread quickly and can lead to death. They didn't - and still don't - know why. This research may yield a clue.

"When most people think of environmental agents, they think of how these agents can CAUSE cancer," Dr. Balla said. "We are proposing that they also act on already established cancers."

In order to test their theory that environmental factors might play a role, Drs. Balla and Lindholm first had find out what made aggressive prostate cancer cells different from dormant cells. During the 1950s, investigators at other centers were able to grow prostate cancer cells in tissue cultures. Medical College researchers have isolated and identified ten genes that are turned on only in aggressive variants of those cells.

Their findings about these aggressive-associated genes and their behavior were presented at the American Association for Research meeting in Philadelphia on April 11, 1999.

Step two in their research is to find out if pollutants in the environment can turn non-aggressive prostate cancer cells into killer cells. They also want to find markers that indicate aggressive cancer behavior, and identify the target molecules in cancer cells to aid in finding a cure.

The researchers are subjecting non-aggressive cancer cells in the lab to environmental pollutants including certain insecticides, cadmium (a heavy metal present in batteries, cigarettes, contaminated water and food) and cigarette smoke tar. "Now we are finding out if some of those ten genes are activated by these environmental pollutants in less aggressive cells also," Dr. Balla said. "We don't know yet what these pollutants would do in experimental animals or in men with prostate cancer; what happens in tissue cultures may not happen in patients, but this is a very good start."

Drs. Balla and Lindholm began their research with a seed grant from the Medical College Cancer Center. They are continuing with a half-million dollar grant from the Environmental Protection Agency. The Medical College is the only place in the country presently studying this problem. Since prostate cancer is the most common male cancer and the second leading cause of cancer death in men in the United States, their research could benefit many.

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