A toxicology suite adapted for comparing parallel toxicity responses of model human lung cells to diesel exhaust particles and their extracts

摘要

Epidemiological studies have shown that exposure to airborne particulate matter can be an important risk factor for some common respiratory diseases. While many studies have shown that particulate matter exposures are associated with inflammatory reactions, the role of specific cellular responses in the manifestation of primary hypersensitivities, and the progression of respiratory diseases remains unclear. In order to better understand mechanisms by which particulate matter can exert adverse health effects, more robust approaches to support in vitro studies are warranted. In response to this need, a group of accepted toxicology assays were adapted to create an analytical suite for screening and evaluating the effects of important, ubiquitous atmospheric pollutants on two model human lung cell lines (epithelial and immature macrophage). To demonstrate the utility of this suite, responses to intact diesel exhaust particles, and mass-based equivalent doses of their organic extracts were examined. Results suggest that extracts have the potential to induce greater biological responses than those associated with their colloidal counterpart. Additionally, macrophage cells appear to be more susceptible to the cytotoxic effects of both intact diesel exhaust particles and their organic extract, than epithelial cells tested in parallel. As designed, the suite provided a more robust basis for characterizing toxicity mechanisms than the analysis of any individual assay. Findings suggest that cellular responses to particulate matter are cell line dependent, and show that the collection and preparation of PM and/or their extracts have the potential to impact cellular responses relevant to screening fundamental elements of respiratory toxicity.