Chronic exposure to polystyrene microplastics increased the chemosensitivity of normal human liver cells via ABC transporter inhibition

Microplastics (MPs) are ubiquitous in environmental compartments and consumer products. Although liver is frequently reported to be a target organ of MP accumulation in mammals, few studies have focused on MP hepatoxicity in humans. In this study, we used normal human liver cells, THLE-2, to assess the acute and chronic toxicity of polystyrene (PS) MPs with sizes of 0.1 and 1 mu m. The results showed that after 48 h of exposure, both kinds of PS MPs could enter THLE-2 cells and cause no obviously acute cytotoxicity at <20 mu g/mL. In contrast, metabolomic analysis revealed that 90 days of PS MPs exposure at environmentally relevant dose (0.2 mu g/mL) could significantly alter the metabolic profiles of the cells, especially the nanosized MPs. KEGG pathway analysis showed that the ATP-binding cassette (ABC) transporter pathway was the most significantly changed pathway. Cell functional tests confirmed that chronic PS MP treatment could inhibit the activity of the ABC efflux transporter and further increase the cytotoxicity of arsenic, indicating that the PS MPs had a chemosensitizing effect. These findings underline the chronic risk of MPs to human liver.