Non-targeted metabolomics of multiple human cells revealing differential toxic effects of perfluorooctanoic acid

Differences in toxic effects of contaminants among human cells are essential for evaluating their health risks to humans. In this study, non-targeted metabolomics of multiple human cell lines (A549 (lung), DLD-1 (intestine) and L-02 (liver) cells) was used to address the differential toxicity of perfluorooctanoic acid (PFOA). The number of differential metabolites (DMs) identified in the PFOA-treated A549 cells (67) was highest, followed by DLD-1 (12) and L-02 cells (10). The categorization of DMs was almost uniquely specific to each of cell lines. PFOA significantly promoted linoleic acid metabolism in L-02 cells whereas this metabolism was inhibited in the PFOA-treated A549 cells. The levels of interleukin (IL)-1β, IL-6, IL-8 and IL-13 were about 1.5 times higher in the PFOA-treated A549 and L-02 cells than in the controls. PFOA stimulated the biosynthesis of arginine and the metabolism of vitamin B6 in A549 cells. Arginine and vitamin B6 supplemented into cell culture effectively decreased the levels of IL-6 and IL-8. The inhibition of purine metabolism by PFOA resulted in the arrestation of DLD-1 cells at the G0/G1-phase. Our results suggest that the differential toxicity of PFOA related to exposure pathways could be elucidated by metabolic profiles specific to various human cells.