Mechanistic toxicity assessment of fine particulate matter emitted from fuel combustion via pathway-based approaches in human cells.

Fuel exhaust particulate matter (FEPM) is an important source of air pollution worldwide. However, the comparative and mechanistic toxicity of FEPMs emitted from combustion of different fuels is still not fully understood. This study employed pathway-based approaches via human cells to evaluate mechanistic toxicity of FEPMs. The results showed that FEPMs caused concentration-dependent (0.1-200 μg/mL) cytotoxicity and oxidative stress. FEPMs at low concentration (10 μg/mL) induced cell cycle arrest in S and G2 phases, while high level of FEPMs (200 μg/mL) caused cell cycle arrest in G1 phase. Different FEPMs induced distinct expression profiles of toxicity-related genes, illustrating different toxic mechanisms. Furthermore, FEPMs inhibited the phosphorylation of protein kinase A (PKA), which related with reproductive toxicity. Spearman rank correlations among the chemicals carried by FEPMs and the toxic effects revealed that PAHs and metals promoted cell cycle arrest in the G1 phase and suppressed PKA activity. Furthermore, PAHs (Nap and Acy) and metals (Al and Pb) in FEPMs were highly and positively correlated with the expression of genes involved in apoptosis, ER stress, metal stress and inflammation. Our findings offered more mechanistic information of FEPMs at the level of subcellular toxicity and help to better understand their potential health effects.