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Asbestos fiber shape may trigger radicals.

Asbestos fiber shape may trigger radicals

Researchers have discovered how one type of asbestos stimulates cells to release oxygen radicals, highly reactive molecules that seem to play a key role in asbestos-related lung diseases.

The finding, described in the August TOXICOLOGY AND APPLIED PHARMACOLOGY, may help researchers develop treatments for a debilitating respiratory condition called asbestosis, says study coauthor Andrij Holian, a molecular toxicologist at the University of Texas Medical School at Houston.

Asbestos can trigger excessive collagen production in the lung that causes asbestosis, explains coauthor Paul L. Roney, now with Versar Inc., an environmental consulting firm in Springfield, Va. Researchers suspect the interaction of asbestos fibers and alveolar macrophages, white blood cells in the lung, triggers the release of superoxide anion, a highly reactive free radical that stimulates production of collagen fibers.

The two major types of asbestos fibers, serpentine and amphibole, have chemical and structural differences that may influence their interactions with cells. In their study, Roney and Holian screened both forms of asbestos for their ability to stimulate alveolar macrophages from guinea pigs to produce superoxide anions. They found that chrysotile fibers, a form of serpentine asbestos, adhered to the surface of guinea pig macrophages. This binding sets off a chain of events, activating an enzyme that cleaves a fat molecule in the cell membrane, which generates two chemical messengers. One elevates calcium levels in the cell; the other sets in motion a chain of enzymatic events that ultimately converts molecular oxygen into oxygen radicals.

"What our research has shown is that chrysotile asbestos is capable of directly activating one of the most important cell signaling pathways," Roney says.

Amphibole forms of asbestos didn't stimulate those pathways in guinea pig cells, the researchers say. But in cells extracted from human volunteers, Holian says, "both fibers stimulate the human alveolar macrophage to produce supreoxide anion." Holian isn't sure how serpentine asbestos stimulates free radical production, but he's confident structural differences between the two fibers influence their reactions with cells.

Holian says research he described in an abstract in the April AMERICAN REVIEW OF RESPIRATORY DISEASE shows that extra-cellular calcium prolongs the asbestos stimulation of the superoxide anion production. He speculates that calcium channel blocker drugs, already used to treat heart disease, might be used to treat asbestosis patients.
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Title Annotation:research into treating respiratory condition asbestosis
Author:Loupe, Diane E.
Publication:Science News
Date:Sep 9, 1989
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