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β-六氯环己烷驱动人正常支气管上皮细胞系 BEAS-2B 的癌变。

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B.

机构信息

Department of Biochemical Sciences "A.Rossi-Fanelli", Sapienza University, P.le A.Moro 5, 00185 Rome, Italy.

Enrico ed Enrica Sovena Foundation, 00199 Rome, Italy.

出版信息

Int J Mol Sci. 2021 May 29;22(11):5834. doi: 10.3390/ijms22115834.

Abstract

Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on β-hexachlorocyclohexane (β-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of β-HCH, already established in our previous studies, the aim of this work is to assess whether β-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM β-HCH. The obtained results strongly support the carcinogenic potential of β-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize β-HCH, which appears to be a full-fledged carcinogenic agent.

摘要

有机氯农药构成了环境污染物的主体,其中许多化合物被发现对人类具有致癌性。在所有这些化合物中,β-六氯环己烷(β-HCH)引起了越来越多的关注,它实际上是六氯环己烷家族中最危险、同时也是研究最少的成员。考虑到β-HCH 具有多方面的生化活性,这在我们之前的研究中已经得到了证实,本工作的目的是评估β-HCH 是否也能引发细胞恶性转化,从而导致癌症的发生。为此,我们用 10µMβ-HCH 处理人正常支气管上皮细胞系 BEAS-2B,进行了相关实验。所得结果强烈支持β-HCH 的致癌潜能,其通过非遗传毒性(致癌信号通路的激活和增殖活性)和间接遗传毒性(ROS 产生和 DNA 损伤)机制来实现,这些机制显著影响细胞的宏观特征和功能,如细胞形态、细胞周期谱和细胞凋亡。考虑到所有这些因素,本研究提供了进一步表征β-HCH 的重要元素,表明其是一种完全的致癌剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bedf/8199278/f8789f451987/ijms-22-05834-g001.jpg

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