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.
Keywords: benzo[a]pyrene; genomic instability; tongue squamous cell carcinoma.
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