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Tumor promoters halt cell-cell 'talk.' (research on cancer-promoting agents)

Tumor promoters halt cell-cell "talk'

A new test for monitoring the ability ofliving, touching cells to chemically "communicate' may ultimately find use as a screening test to identify chemicals involved in causing cancer. Developed by scientists at Michigan State University in East Lansing, it uses a laser-fluorescence microscope system to peer inside cells growing in culture.

At the American Chemical Society'sspring national meeting in Denver this week, John Holland, a developer of the laser microscope system, described his instrument and its use in demonstrating the ability of some 100 known cancer-promoting agents--including phorbol esters (plant hormones), DDT, PCBs and saccharin--to shut down the transfer of chemical signals between adjacent cells. According to Holland, this signal shutdown may help explain why cancers are characterized by unregulated cell proliferation.

Carcinogenesis is believed to be amultistage process, initiated when exposure to some toxic agent triggers long-lived changes in a cell. The process is advanced by the cell's subsequent exposure to a promoting agent, which may not be carcinogenic by itself.

Ordinarily, healthy cells grow rapidlyonly until they begin touching. Then some mechanism triggers the cells suddenly to stop growing. Holland says it may be that chemical communications between touching cells serve as a stop-growth cue. If so, when these signals are blocked--as by tumor promoters-- affected cells could become deaf to the "stop proliferating' message.

The new test measures cell-to-cell communicationsby showing the movement of a fluorescing dye. Starting as an electrically neutral molecule, the dye can pass through cell membranes. Inside cells, however, enzymes cleave the dye into charged ions that can no longer pass through intact cell membranes. The only way for this dye signal to pass to another cell is through a pore-like "gap junction' that naturally forms to bridge touching cells.

Using the microscope, the researchersfocus a laser beam on a 1/25,000-inch spot. Where it shines on dye, a fluorescing spot appears whose intensity is calibrated by the computer. After destroying the dye in one of a pair of adjacent cells, the researchers watch to see whether the dye in the other cell diffuses back into the first.

Tests headed by James Trosko showedthat the dye won't move between cells that have been exposed to a cancer promoter--indicating damage to the gap junction, according to Holland. None of the dozens of non-cancer-promoting chemicals tested caused a similar breakdown.

If the association between tumor promotersand a communications shutdown proves universal and reliable, the scientists say, many carcinogen-screening studies presently using animals may be replaced by these much simpler, quicker, less costly and more easily interpreted cell-culture studies. "This test could reduce by a factor of 100 the number of animals needed' to identify new cancer promoters, says Holland.

Moreover, he says, data collected in thepast few weeks by Trosko suggest that tumor promoters fall into discrete classes of potency--classes that appear to be differentiated by their mechanism in disrupting cell communications.
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Author:Raloff, Janet
Publication:Science News
Date:Apr 11, 1987
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