| Epidemiological studies have provided compelling statistical evidence for associations between airborne particulate matter (PM) exposures and negative health effects. Additionally, numerous toxicological studies have demonstrated that beyond certain thresholds, airborne PM has the potential to introduce DNA damage, cytotoxicity and oxidative stress in mammalian cells. More recent toxicological research on indoor and outdoor PM focuses on individual biomarker analyses, often generalizing cellular damage pathways to solitary mechanisms. There is a need to develop broader screening approaches, which can more comprehensively describe the conglomerate biological activity that PM may convey to respiratory exposure. In response to this need, a suite of toxicological assays was adapted to assess major toxicological modes associated with common PM classes. To this end, the analytical panel developed here employed human cell lines (lung epithelial and phagocytic monocytes) to address the following modes of fundamental cellular responses previously linked with PM exposure: necrotic and apoptotic cytotoxicity, genotoxicity and oxidative stress. The assays utilized were optimized to be relatively rapid, while delivering high confidence in identifying individual toxicity mechanisms, as well as clear indications of the potential for synergistic effects.;A cohort of dose-response relationships was established for diesel exhaust particles (DEP) and diesel exhaust extracts which demonstrated clear modal differences in DEP's ability to exert toxicological effects in human lung cells lines. This approach was extended to include a model bioaerosol (glucan), and combinations of DEP and bioaerosol. The results of this suite presented converging lines of evidence for synergist toxicological effects resulting from the co-exposure of common bioaerosol components with diesel exhaust. |
