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丙烯醛通过刺激 DNA 损伤诱导的细胞凋亡对间质细胞发挥遗传毒性作用。

Acrolein exerts a genotoxic effect in the Leydig cells by stimulating DNA damage-induced apoptosis.

机构信息

Department of Biology, Faculty of Science, Istanbul University, Vezneciler, 34134, Istanbul, Turkey.

出版信息

Environ Sci Pollut Res Int. 2020 May;27(13):15869-15877. doi: 10.1007/s11356-020-08124-5. Epub 2020 Feb 24.

DOI:10.1007/s11356-020-08124-5
PMID:32090303
Abstract

Acrolein is a highly reactive unsaturated organic molecule and has harmful effects on human health. Acrolein is generally formed in heat-treated foods above 150 °C, as well as in the combustion of gasoline, wood industry, plastic waste, and tobacco smoke. In this study, the effects of acrolein on genotoxicity in Leydig cells and the underlying mechanisms are aimed to be clarified. In addition, the toxicogenomic profile of acrolein was studied in terms of both apoptosis and steroidogenesis. Real-time PCR and ELISA tests were used to analyses of steroidogenic endpoints. Apoptosis was evaluated with double fluorescence staining and gene expression analyses of related genes. Comet assay was used to determine the genotoxicity. The results showed that acrolein caused concentration-dependent inhibition on cell viability at 8 μM and above concentrations, decreased testosterone production at 13.6 and 19.7 μM concentrations, and suppressed expression levels of genes that play an important role in steroidogenic pathway. Furthermore, acrolein downregulated expression of anti-apoptotic Bcl2 gene and upregulated expression of pro-apoptotic Bax, Casp3, and Trp53 gene after 24-h treatment in 7.4, 13.6, and 19.7 μM acrolein-exposed Leydig cells. The results of comet assay showed that acrolein significantly induced tail length, tail % DNA, and Olive tail moment. Overall, it was concluded that acrolein-induced cell damage in Leydig cells may be due to formation of genetic damage in steroidogenesis and apoptosis.

摘要

丙烯醛是一种具有高反应性的不饱和有机分子,对人类健康有害。丙烯醛通常在 150°C 以上的热处理食品中形成,以及在汽油燃烧、木材工业、塑料废物和烟草烟雾中形成。在这项研究中,旨在阐明丙烯醛对睾丸间质细胞遗传毒性的影响及其潜在机制。此外,还研究了丙烯醛在凋亡和类固醇生成方面的毒代基因组特征。实时 PCR 和 ELISA 测试用于分析类固醇生成终点。通过双荧光染色和相关基因的表达分析评估凋亡。彗星试验用于确定遗传毒性。结果表明,丙烯醛在 8μM 及以上浓度下可引起浓度依赖性的细胞活力抑制,在 13.6μM 和 19.7μM 浓度下可降低睾酮的产生,并抑制在类固醇生成途径中起重要作用的基因的表达水平。此外,丙烯醛在 7.4μM、13.6μM 和 19.7μM 丙烯醛暴露的睾丸间质细胞中,在 24 小时处理后下调抗凋亡 Bcl2 基因的表达,上调促凋亡 Bax、Casp3 和 Trp53 基因的表达。彗星试验的结果表明,丙烯醛显著诱导尾长、尾%DNA 和 Olive 尾矩。总体而言,结论是丙烯醛诱导的睾丸间质细胞损伤可能是由于类固醇生成和凋亡中的遗传损伤形成所致。

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