How Free Radicals Abet a Cancer rascal

Ras gets radical.

When a waiter suggests the salad bar, there is a good reason to load up on the greens: They're full of antioxidants thought to sop up free radicals, corrosive molecules that already had a bad reputation because they can damage DNA and perhaps lead to cancer. Now researchers report in today's issue of Science* that one kind of free radical also helps a protein called Ras transmit a signal that stimulates normal cell growth and--when it goes haywire--sparks the uncontrolled cell division leading to cancer.

Ras sends its growth-stimulating message to the nucleus through superoxide, as well as through the MAP kinases (MAPK and MAPKK).
A team led by Pascal Goldschmidt-Clermont, a cardiologist at Ohio State University in Columbus, measured the levels of superoxide--a free radical made of an oxygen molecule with an extra electron--in cultured mouse cells. Team members found that cells with a mutated ras gene--one that causes the cell-division pathway to get stuck in the "on" position--produce more superoxide than do cells with the normal ras gene. Chemically blocking the pathway sharply reduced superoxide concentrations. When the team treated cells to produce less superoxide in response to Ras, the DNA replication during cell division abated, suggesting that superoxide stimulates DNA synthesis.

Other experts are intrigued by the finding. Roger Davis, a cell biologist at the University of Massachusetts Medical Center in Worcester, predicts that linking oxygen free radicals to Ras-activated growth "will cause a lot of people to rethink the mechanisms of growth control." What's more, says cell biologist Marc Symons of Onyx Pharmaceuticals in Richmond, California, because the Ras pathway can spur tumor growth, "the elements in [this] pathway are all good [anticancer] drug targets."

* For more details, Science Online subscribers can link to the full text of the Report.

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