Benzo(a)pyrene [B(a)P], which is a carcinogen, is a substance most typically known in cigarette smoke and considered as an important intermediary of lung cancer. The enzyme CYP1A1 is crucial for the metabolic conversion of B(a)P into the intermediates that induce carcinogenesis. Stimulation of the aryl hydrocarbon receptor, which is regulated by B(a)P, is thought to induce numerous signaling cascades. Interruption in the mitogen‐activated protein kinase (MAPK) pathway causes changes in cellular processes and may alter the AhR pathway. The aim of this investigation is to examine the potential ability of a flavonoid pinocembrin (PCB) to alleviate B(a)P toxicity and analyze the underlying molecular mechanisms. We found that PCB inhibited DNA adduct formation by attenuating CYP1A1 expression through the suppression of the AhR/Src/ERK pathways. PCB mitigated the B(a)P‐stimulated DNA damage, inhibited Src and ERK1/2 expression, decreased CYP1A1 expression, and reduced the B(a)P‐induced stimulation of NF‐κB and MAPK signaling in lung epithelial cells. Finally, the activity of CYP1A1 and Src in lung tissues from mice supplemented with PCB was noticeably decreased and lower than that in lung tissues from mice supplemented with B(a)P alone. Collectively, these data suggest that PCB may alleviate the toxic effects of PAHs, which are important environmental pollutants.

中文翻译：

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Pinocembrin通过多种途径减弱苯并（a）induced诱导的CYP1A1表达

苯并（一py [B（a）P]是致癌物，是卷烟烟雾中最常见的物质，被认为是肺癌的重要媒介。CYP1A1酶对于B（a）P代谢转化为诱导癌变的中间体至关重要。由B（a）P调节的芳烃受体的刺激被认为诱导了许多信号级联反应。丝裂原激活的蛋白激酶（MAPK）途径的中断会导致细胞过程发生变化，并可能改变AhR途径。这项研究的目的是检查类黄酮pinocembrin（PCB）减轻B（a）P毒性的潜在能力，并分析潜在的分子机制。我们发现PCB通过抑制AhR / Src / ERK途径来减弱CYP1A1的表达，从而抑制DNA加合物的形成。PCB减轻B（a）P刺激的DNA损伤，抑制Src和ERK1 / 2表达，降低CYP1A1表达，并减少B（a）P诱导的肺上皮细胞对NF-κB和MAPK信号的刺激。最后，CYP1A1和Src活性在添加了PCB的小鼠的肺组织中显着降低，并且低于单独添加了B（a）P的小鼠的肺组织中的CYP1A1和Src活性。总体而言，这些数据表明PCB可以减轻PAH的毒性作用，PAH是重要的环境污染物。CYP1A1和Src的活性在单独添加PCB的小鼠的肺组织中显着降低，并低于单独添加B（a）P的小鼠的肺组织中的CYP1A1和Src活性。总体而言，这些数据表明PCB可以减轻PAH的毒性作用，PAH是重要的环境污染物。CYP1A1和Src的活性在单独添加PCB的小鼠的肺组织中显着降低，并低于单独添加B（a）P的小鼠的肺组织中的CYP1A1和Src活性。总体而言，这些数据表明PCB可以减轻PAH的毒性作用，PAH是重要的环境污染物。