Despite numerous studies on the toxicities of planar polycyclic aromatic hydrocarbons (PAHs), very little is known about the toxicological profiles of non-planar PAHs. In the present study, the cytotoxicity of corannulene (COR), a typical bowl-shaped PAH with a myriad of applications in the area of material chemistry, and benzo[a]pyrene (BaP), a typical planar PAH with similar molecular weight, were systematically compared in various cell lines. Compared with BaP, exposure to COR resulted in less cytotoxic responses in both human (HepG2) and murine (Hepa1-6) hepatoma cells, which was characterized with a slower cellular accumulation as well as a weaker induction of cytochrome P450 1 (CYP1/Cyp1) isozymes. Knockdown of aryl hydrocarbon receptor (AhR) by siRNA attenuated the inductive effect of COR on CYP1A/Cyp1a mRNA levels in these two cell lines. Further analysis revealed that derivatization greatly influenced the cytotoxicity of COR, which was positively correlated with their binding affinities to the AhR, as demonstrated by in silico molecular docking. Overall, these results suggest that AhR appears to be involved in the cytotoxic responses of COR and its derivatives, providing a fundamental understanding of the biological effects of bowl-like PAHs.

中文翻译：

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芳烃受体参与玉米蒌烯及其衍生物的细胞毒性

尽管对平面多环芳烃 (PAH) 的毒性进行了大量研究，但对非平面多环芳烃的毒理学特征知之甚少。在本研究中，corannulene (COR) 是一种在材料化学领域具有广泛应用的典型碗状多环芳烃，而苯并 [a] 芘 (BaP) 是一种具有相似分子量的典型平面多环芳烃，在各种细胞系中进行了系统比较。与 BaP 相比，暴露于 COR 导致人 (HepG2) 和鼠 (Hepa1-6) 肝癌细胞的细胞毒性反应较少，其特征是细胞积累较慢，并且对细胞色素 P450 1 (CYP1/Cyp1) 的诱导较弱) 同工酶。siRNA 对芳烃受体 (AhR) 的敲低减弱了 COR 对这两种细胞系中 CYP1A/Cyp1a mRNA 水平的诱导作用。进一步的分析表明，衍生化极大地影响了 COR 的细胞毒性，这与它们对 AhR 的结合亲和力呈正相关，如硅分子对接所证明的那样。总体而言，这些结果表明 AhR 似乎参与了 COR 及其衍生物的细胞毒性反应，提供了对碗状多环芳烃的生物学效应的基本理解。