Cumulative metabolic effects of low-dose benzo(a)pyrene exposure on human cells

Benzo(a)pyrene (B[a]P) is a common environmental and foodborne pollutant which has been identified as a Group I carcinogen. Although the carcinogenicity of B[a]P has been illustrated, its comprehensive influence on metabolism and further relevance in adverse health outcomes are not well understood. To investigate the global metabolic effects of long-term B[a]P exposure at environmental dosage, we utilized the human SMMC-7721 cell-based B[a]P exposure models to perform a metabolomics study and network analysis. A total of 316 biochemicals were identified and 104 metabolites were found to be significantly altered. Bioinformatics analysis showed that the amino acid, carbohydrate, and lipid metabolism pathways and the nucleotide metabolism pathway were influenced by prolonged B[a]P exposure. Notably, the metabolic effects of B[a]P varied with different dosages. In addition, B[a]P exposure caused a decline in the glycolysis process but enhanced the glycolytic capability of SMMC-7721 cells in vitro. These findings establish the overall B[a]P-induced metabolic network, characterize the metabolic effects of chronic and environmental B[a]P exposure on human-relevant cells, and enhance the understanding of the adverse outcome pathway frame of B[a]P.