Mutations Surge in Jam-Packed Cells

Cancer cells mutate rapidly, enabling them to outwit drugs and survive inhospitable conditions in the body. Scientists have generally thought that the rapid cell division in tumors is to blame, with the mutations resulting from errors as the cells copy their DNA. But it now seems that colon cancer cells, at least in a petri dish, have a different way to boost their mutation rate, which they can simply switch on in response to adverse conditions. The mechanism behind the dramatic rise, reported in tomorrow's issue of Science*, is a mystery.

Mark Meuth, a molecular geneticist at the University of Utah, Salt Lake City, was puzzled by an exception to the rule of rapid mutation in cancer cells: a cell line from a human colon cancer that when grown in a dish mutated at the same low rate as noncancerous cells. This was especially surprising because the cell line, called 2774, has a defective DNA repair mechanism; other cells with this defect accumulate mutations rapidly.

The mutation rate shot up, however, when Burt Richards, a scientist in Meuth's lab, accidentally allowed a dish of the tumor cells to overgrow. When the team left dishes of cells crowded for 2 weeks, they found that one highly mutating gene, called HPRT, had mutated 7900 times faster than in cells grown at low density, even though the crowded cells weren't dividing. Another cell line, also from colon cancer and called SK-UT-1, boosted its HPRT mutation rate 34 times after reaching a high concentration of cells.

Meuth says he doesn't know why the overcrowded cells mutate so readily, but he suspects that an adverse environment around the cells, such as the lack of nutrients or oxygen in cramped conditions, somehow switches on some mutation mechanism. Lawrence Loeb, a pathologist at the University of Washington, Seattle, says that if the researchers can discover the mechanism of the increased mutation rate, it could provide a new avenue of treatment for any cancer cell that uses it. "If the increase is due to something simple such as oxygen free radicals, we could give antioxidants," he says.

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