Effects of the butadiene metabolite diepoxybutane on endothelial cell and platelet function

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Butadiene, is used in the synthesis of rubber and is also found in cigarette smoke and car exhaust. It is a carcinogen and is also associated with cardiovascular disease. The most toxic metabolite, 1,4‐diepoxybutane (DEB), forms adducts with biomolecules. Consequently, we determined the effects of DEB on the function of endothelial cells and platelets. Human endothelial cells (EC) were exposed to 1 ‐10 μM DEB for 3‐7 days. DEB‐exposed EC were examined by FACS for cell surface expression of adhesion molecules, and for leukocyte transmigration. Dose‐dependent increases in ICAM‐1 (25%, P< 0.01 at 5 µM) and VCAM‐1 (30%, P< 0.01 at 5 µM) were observed. A dramatic increase in leukocyte transmigration (125%, P<0.01) through a monolayer of DEB‐treated EC was also observed. Cell proliferation was completely blocked by 4 days at 10 µM DEB and EC developed a morphology resembling senescent cells. However, EC that were treated for 7 days could still form endothelial tubes on matrigel. For platelets, human platelet rich plasma was treated with DEB for 1 hour and the effects on the rates of aggregation were determined by aggregometry. Significant concentration‐dependent increases in the rates of both thrombin‐ (35% P<0.01 at 5 μM) and collagen‐ (22% P<0.01 at 5 μM) induced activation were observed. These results indicate that butadiene exposure can cause inhibition of EC growth while augmenting ICAM‐1, VACM‐1, and platelet activity and retaining EC angiogenic capacity.