Benzo[ a ]pyrene promotes progression in tongue squamous cell carcinoma

Objectives Benzo[a]pyrene (B[ a ]P) is a member of the polycyclic aromatic hydrocarbon (PAH) family. Although the potent carcinogenicity of high‐dose B[ a ]P has been extensively reported, the effects of long‐term exposure to B[ a ]P on the progression of tongue squamous cell carcinoma (TSCC) are poorly understood. Methods In the present study, TSCC cells were treated with 5 or 50 nM of B[ a ]P for three months. The proliferation and chemoresistance of B[ a ]P‐treated cells to 5‐fluorouracil or cisplatin were detected by CCK8. The motility of the B[ a ]P‐treated cells was evaluated with wound healing analysis, invasion assay, and three‐dimensional culture in decellularized mouse tongue matrix. Xenograft assay was used to investigate the aggressiveness of B[ a ]P‐treated cells. Immunofluorescence staining, terminal restriction fragment assay, and whole‐genome sequence were used to determine the mutation spectrums. Results Long‐term 50 nM B[ a ]P‐treated cells exhibited increased aggressiveness and chemoresistance to 5‐fluorouracil or cisplatin. In addition, data from whole‐genome sequencing demonstrated that C:T to A:T transitions were the predominant nucleotide substitutions occurred in 50 nM B[ a ]P‐treated CAL27 cells. Furthermore, 102 non‐synonymous or stop‐gain mutations were enriched in the extracellular‐matrix‐receptor interactive pathway. Conclusions B[ a ]P exposure may contribute to genomic instability, and therefore, B[ a ]P may promote the progression of TSCC.