PFOA and PFOS-induced oxidative stress response in human microvascular endothelial cells.
Qian-Y; Ducatman-A; Leonard-S; Ward-R; Vallyathan-V; Castranova-V
Toxicologist 2010 Mar; 114(1):48
Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are the two most widely known perfluorinated chemicals (PFCs), which contain an eight-carbon backbone. They are man-made fluorocarbon-based acids that have been used in various industrial processes. They are non-biodegradable and persistent in the human body and environment. They are released directly from production processes, as well as from their use in manufacturing of new products. Human occupational and environmental exposure to PFOA and PFOS occurs globally. Accumulating surveillance data suggest associations between PFOA and PFOS exposures and adverse effects on human health, including lipid metabolism, uric acid metabolism, and reproductive risks. Whether these biomonitoring associations are etiologic remains a question. In this study, we demonstrated that exposure of human microvascular endothelial cells (HMVECs) to PFOA and PFOS induces the production of reactive oxygen species (ROS) at both high and low concentrations in a time-dependent manner. We have also found that PFOA exposure induces the production of ROS in a dose-dependent manner. Morphologically, we have found that exposure to PFOA and PFOS induces actin filament remodeling, endothelial permeability changes, and endothelial migration and in vitro enhancement of angiogenesis in HMVECs. Furthermore, we have demonstrated that the production of ROS plays a regulatory role in PFOA- and PFOS-induced actin filament remodeling and endothelial migration and permeability increase. Taken together, our results indicate that PFOA- and PFOS-induced ROS production may play a role in the aberrations of endothelial permeability barrier integrity. The results from this study may contribute to dissecting the molecular mechanisms involved in PFOA and PFOS toxicity.
Biological-effects; Cell-biology; Cellular-reactions; Chemical-composition; Chemical-hypersensitivity; Chemical-properties; Exposure-assessment; Exposure-levels; Exposure-methods; Health-hazards; Humans; Microbiology; Molecular-biology; Occupational-exposure
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah