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An apple a day keeps the doctor away, right? Actually, the evidence is much more convincing that a healthy serving of broccoli a day may keep the oncologist away. Researchers have identified a number of natural substances, many in vegetables, that seem to protect against cancer. Now, they've figured out just how the veggies do it, a finding that may lead to ways to boost human resistance to the deadly disease.
Scientists from Johns Hopkins University in Baltimore and Japan's Tsukuba University believe that they have discovered the chemical mechanism that allows the body to protect itself from the effects of carcinogens and other harmful chemicals. "We've gained long-awaited proof of a basic mechanism that can reduce the risk of cancer," says Paul Talalay, a molecular pharmacologist at Johns Hopkins.
MALIGNANCY SHIELD. The key line of defense is a group of chemical catalysts, called phase II enzymes, that block toxins' ability to damage DNA and to trigger cancer. Some natural chemicals, such as one called sulforaphane that's found in broccoli, seem to trigger this system of "chemoprotection," causing the body to produce high levels of the beneficial enzymes. Researchers looked for genes that contain code for the production of various enzymes but reported inconclusive results.
The new research, which was reported on Mar. 12 in the Proceedings of the National Academy of Sciences, points to a universal molecule -- a protein known as Nrf2 that seems to act like a dimmer switch for cells. Increase levels of the protein in the body, and it turns up protection in the presence of carcinogens. Earlier research by Masayuki Yamamoto, a molecular biologist from Tsukuba University, showed that protective chemicals, such as those in plants, work by sparking cells' release of Nrf2. The protein then activates a DNA sequence common to the genes of all phase II enzymes, turning them all on.
To test the idea, the researchers created a strain of genetically engineered mice that lacked the ability to produce Nrf2. Their levels of phase II enzymes plummeted. Next, they exposed groups of mice with and without the genetic switch to a potent carcinogen found in cigarette smoke -- benzpyrene. While both groups developed tumors, those without Nrf2 had significantly more.
CLINICAL TRIALS. In a further experiment, mice exposed to the carcinogen were given a drug called oltipraz that's used to treat parasite infections but had been shown in earlier tests to increase levels of phase II enzymes and reduce cancer risk. The drug cut the number of tumors in normal mice in half. Those without Nrf2's protection were ridden with tumors, even with the drug. "Without the switch, the mice couldn't be protected," says Yamamoto.
Johns Hopkins team leader Thomas W. Kensler is wasting no time in seeing if the findings can be put to practical use -- he's already heading clinical trials of one chemoprotective drug in China and plans long-term clinical studies that should reveal a lowered incidence of cancer. "With slight changes in the switch, you can get a tremendous step up in a body's sensitivity to cancer agents," he asserts. "We have evidence that we can increase the levels of protection in people."
The research also promises to provide clues to why some people are more susceptible to cancer than others. And it may also offer a new way to test the effects of cancer-causing chemicals. "By turning down an organism's ability to squelch carcinogens, you get an exquisitely sensitive testing method, say, for which pollutants in the Chesapeake Bay cause tumors to form."
But until an anticancer pill exists that's the equivalent of an aspirin a day to fend off heart disease, we'll be left to our bodies' natural defenses. And we'll be doing ourselves a favor by giving our bodies a time-honored "broccoli boost."
By Alan Hall in New York Edited by Douglas Harbrecht
Copyright 2001 , by The McGraw-Hill Companies Inc. All rights reserved.
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