Abstract 132: Biomarkers of Cardiovascular Toxicity Following Benzene Exposure

Abstract

Benzene is a ubiquitous environmental pollutant abundant in plastics, petroleum products and cigarette smoke. Although hematopoietic and hepatic toxicity of benzene has been extensively studied, little is known about the effect of benzene on cardiovascular health. In this study, we assessed benzene exposure in a cohort of 210 participants with moderate to high CVD risk by measuring urinary benzene metabolite - trans, trans-muconic acid (t,t-MA). After adjusting for confounding variables we observed a 9% decrease in circulating levels of both early (AC133+) and late (AC133-) angiogenic cells for every 0.1mg t,t-MA/g creatinine increase in the urine. Uriniary t,t,MA levels were also positively associated with hyperlipidemia (P<0.02). Although smoking was associated with higher urinary levels of, t,t-MA, the association between benzene exposure and CVD risk was independent of smoking. In non-smokers, t,t-MA levels were positively associated with increased Framingham Risk Scores. Next, we examined the association of surrogate markers of cardiovascular functions and injury in male C57BL/6 mice exposed to HEPA-filtered air or benzene (50 ppm) for 6 hours/day for two (n=34/treatment) or six weeks (n=20/treatment). Both at two and six weeks of exposure to benzene increased fasting plasma glucose (13%, P<0.05), fasting insulin (39%, P<0.05) and HOMA-IR (72%, P<0.05); and platelet-leukocyte aggregates (PLAggs), a marker of platelet activation in vivo. This was accompanied by 26% decrease (P<0.05) in hepatic reduced glutathione level and activation of NF-κB in the liver and skeletal muscle. Moreover, after 6 weeks of benzene exposure plasma LDL and HDL were increased by 25% (P<0.05) and 5% (P<0.05) respectively; circulating endothelial microparticles were increased by 60% (P<0.05); and blood endothelial progenitor cells (EPCs) were decreased by 52% (P<0.05). These data suggest that exposure to benzene is associated with potential deficits in vascular repair and increased CVD risk.