ORGANIC-SOLVENTS ACTIVATE HUMAN PLATELETS THROUGH THE INOSITOL LIPID-LINKED SIGNAL-TRANSDUCTION SYSTEM

It has recently been proposed that occupational exposure to organic so lvents in vivo may lead to platelet activation and this has been subst antiated by exposure of platelets to solvents in vitro. The present wo rk was undertaken to study the effects of organic solvents on the plat elet inositol lipid signal transduction system. Human platelets that h ad been prelabelled with [P-32]P-1 were exposed to a saturated atmosph ere of the organic solvents toluene, xylene or hexane. Extracts were a nalyzed for metabolites of the polyphosphoinositide cycle and ATP. AU solvents studied induced a decrease in radioactivity in phosphatidylin ositol 4,5-bisphosphate together with an increase in radioactivities i n phosphatidylinositol 4-phosphate and phosphatidic acid. This is comp atible with solvent-induced activation of the cells through the inosit ol lipid pathway. In cells exposed to toluene or xylene we could detec t an increased level in inositol trisphosphates at 3 min of exposure. The solvent-induced changes in metabolic ATP could not explain the sol vent-induced effects on the inositol lipid metabolism. It is concluded that the organic solvents toluene, xylene and hexane can activate hum an platelets through the inositol lipid-linked transmembrane signal sy stem.