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Induction of molecular endpoints by reactive oxygen species in human lung cells predicted by physical chemical properties of engineered nanoparticles
Ross, J., G. Nelson, C. Jones, AND S. Thai. Induction of molecular endpoints by reactive oxygen species in human lung cells predicted by physical chemical properties of engineered nanoparticles. American Association for Cancer Research Annual Meeting, Washington, DC, April 01 - 05, 2017.
This research, conducted under CSS 18.02, was designed to identify the properties of engineered nanomaterials that are associated with increased risk for adverse health effects. The data presented here demonstrate that for six different titanium oxide and two different cerium oxide nanomaterials assessed in vitro in human respiratory cells, assays for molecular sequelae of reactive oxygen species are about ten-fold more sensitive than cytotoxicity assays. Further, multiple regression identifies that the relative extents of ROS-associated molecular changes are predicted by trace levels of metals present in the nanomaterials.
A series of six titanium dioxide and two cerium oxide engineered nanomaterials were assessed for their ability to induce cytotoxicity, reactive oxygen species (ROS), and various types of DNA and protein damage in human respiratory BEAS-2B cells exposed in vitro for 72 hours at several concentrations. Although only limited cytotoxicity was observed at concentrations up to 300 µg/ml for all of the nanomaterials, significant increases in 8-oxo-deoxyguanosine, lipid peroxidation mediated protein adducts, and endogenous DNA adducts measured by 32P-postlabeling were detected at concentrations as low as 30 µg/ml, suggesting that molecular changes associated with ROS induction may provide a better means of assessing the low-dose hazards posed by nanomaterials. To identify molecular properties predictive of the ability of nanoparticles to induce ROS sequelae, a least absolute shrinkage and selection operator multiple regression approach has been used to identify relationships between assay outcomes and nanoparticle physical/chemical properties, including particle size, surface area, zeta potential, and elemental analysis. For several of the assay endpoints examined, concentrations of trace metals in the nanoparticles appear to be better predictors of assay outcomes than physical properties. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.