Food-Relevant Polycyclic Aromatic Hydrocarbons Disrupt Intestinal Barrier and Xenobiotic Metabolism in Mouse, Pig, and Human Epithelial Cells.
TL;DR
Because BaP may not fully account for the toxicity of all PAHs, this study provides relevant quantitative benchmarks for intestinal toxicity, advancing knowledge on current PAH exposure risk assessment.
Abstract
Despite their well-established carcinogenicity, the effects of dietary polycyclic aromatic hydrocarbons (PAHs) on intestinal cells remain poorly understood. Additionally, toxicity studies are often based on animal models, and interspecies differences in xenobiotic metabolism may limit extrapolation to human exposure. The cytotoxic and toxicogenomic effects of seven food-relevant PAHs-benz[a]anthracene (BAA), benzo[a]pyrene (BaP), benzo[b]fluoranthene (BBF), benzo[k]fluoranthene (BKF), chrysene (CHRY), indeno[1,2,3-cd]pyrene (INDE), and dibenz[a,h]anthracene (DBAHA)-were investigated in mouse (C57BL/6), pig (IPEC-J2), and human (HIEC-6) intestinal epithelial cells. Viability assays showed that the LC50 values of the PAHs for the mouse and pig models were 5-7 and 6-9 μg/mL, respectively, compared with 12-17 μg/mL in human cells. A conserved transcriptional response to PAH exposure was observed across all cell lines, including upregulation of xenobiotic metabolism genes (ahr, cyp1a1, cyp1b1, gst) and proliferation gene marker (ki67), and downregulation of barrier and junction genes (muc2, cdh1). PAH-treated HIEC-6 cells showed metabolic activation, with cyp1a1 and cyp1b1 upregulated more than 32-fold. Immunofluorescence microscopy experiments supported our findings of decreased MUC2 protein after PAH treatment. Because BaP may not fully account for the toxicity of all PAHs, our study provides relevant quantitative benchmarks for intestinal toxicity, advancing knowledge on current PAH exposure risk assessment.
