Abstract

Benzo(a)pyrene (BaP) is a representative polycyclic aromatic hydrocarbon (PAH) compound, which has been implicated in cancer initiation and promotion. Although BaP is one of the most extensively studied pollutants, the underlying mechanisms through which BaP affects reactive oxygen species (ROS)/hypoxia-inducible factor 1α (HIF-1α)/heme oxygenase 1(HO-1) signaling during lung or breast carcinogenesis are not yet fully understood. In this study, we analyzed the effects of 0 (control), 1, 5, or 25 µM BaP exposure on A549 and MCF-7 cancer cells, by evaluating cell viability, cell cycle, and regulatory protein expression, metabolic gene expression, and ROS/HIF-1α/HO-1 signaling. Cell viability increased following exposure to 1 and 5 µM BaP in A549 cells but decreased following exposure to all concentrations of BaP in MCF-7 cells. BaP significantly increased the proportions of cells in S and G2/M phases, with concomitant reductions in the proportions of cells in G0/G1 phase, following 5 and 25 µM exposure, which was accompanied by the upregulation of the regulatory proteins cyclin A, cyclin B, cyclin-dependent kinase (CDK)1, and CDK2. The subsequent upregulation of cytochrome p450 (CYP)1A1, CYP1B1, CYP3A4, epoxide hydrolase (EH), aldo-keto reductase (AKRC1) expression, and the attenuation of multi-drug resistance protein 4 (MRP4), glutathione-S-transferase (GST)1A1, and GST1B1 were also observed in both cell lines. Moreover, the induction of ROS and the modulation of HIF-1α and HO-1 were observed after BaP exposure. Taken together, these findings suggest that BaP affects proliferation with reference to metabolic genes and ROS/HIF-1α/HO-1 signaling in A549 and MCF-7 cancer cells.

摘要

苯并（a）芘（BaP）是一种具有代表性的多环芳烃（PAH）化合物，与癌症的发生和促进有关。尽管 BaP 是研究最广泛的污染物之一，但 BaP 在肺癌或乳腺癌发生过程中影响活性氧 (ROS)/缺氧诱导因子 1α (HIF-1α)/血红素加氧酶 1(HO-1) 信号传导的潜在机制还没有完全理解。在这项研究中，我们通过评估细胞活力、细胞周期和调节蛋白表达、代谢基因表达和ROS/HIF-1α/HO-1 信号。在 A549 细胞中暴露于 1 和 5 µM BaP 后细胞活力增加，但在 MCF-7 细胞中暴露于所有浓度的 BaP 后细胞活力降低。BaP 显着增加 S 和 G2/M 期细胞的比例，同时 G0/G1 期的细胞比例在 5 和 25 µM 暴露后降低，同时伴随着调节蛋白 cyclin A、cyclin 的上调B，细胞周期蛋白依赖性激酶 (CDK)1 和 CDK2。随后上调细胞色素 p450 (CYP)1A1、CYP1B1、CYP3A4、环氧化物水解酶 (EH)、醛酮还原酶 (AKRC1) 的表达，并减弱多药耐药蛋白 4 (MRP4)、谷胱甘肽-S-转移酶 (在两种细胞系中也观察到 GST)1A1 和 GST1B1。此外，在 BaP 暴露后观察到 ROS 的诱导和 HIF-1α 和 HO-1 的调节。综合起来，