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丙烯醛处理的肺腺癌细胞中 DNA 损伤基因的反应。

Response of DNA damage genes in acrolein-treated lung adenocarcinoma cells.

机构信息

College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX, 77004, USA.

Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, 1102 Bates St. Feigin Center, Houston, TX, 77030, USA.

出版信息

Mol Cell Biochem. 2019 Jan;450(1-2):187-198. doi: 10.1007/s11010-018-3385-x. Epub 2018 Jul 2.

Abstract

Acrolein is a α-β-unsaturated aldehyde and is toxic to human upon its exposure from the environment. Sources of exposure to acrolein can be from heating cooking oil, automobile exhaust, tobacco smoke, and plastic waste. Acrolein exposure to lung is a major concern because of its volatile nature and due to its presence in the urban atmospheric air. Acrolein being highly reactive forms DNA and protein adducts, thereby making the cells vulnerable to long-term damage. Such long-term effect can lead to high susceptibility towards malignant transformation as has been reported in cigarette smokers. The response of DNA damaging genes by acrolein can perhaps give an insight to the cause of damage in the DNA by acrolein. The aim of this study was to examine the response of the DNA damage responsive genes by acrolein in A549 lung adenocarcinoma cells. Acrolein treatment at IC50 concentration showed a robust response of the DNA repair genes but eventually failed to rescue the cells from undergoing apoptosis. The cells pretreated with acrolein and followed by growing the same cells in fresh medium in the absence of acrolein did not help the cells to proliferate. These results conclude that exposure to acrolein marks long-lasting damage to DNA, irrespective of the DNA repair response.

摘要

丙烯醛是一种α-β-不饱和醛,在环境中暴露时对人体有毒。丙烯醛的暴露源可以来自加热食用油、汽车尾气、烟草烟雾和塑料废物。由于其挥发性和存在于城市大气空气中,丙烯醛对肺部的暴露是一个主要关注点。丙烯醛具有高反应性,会形成 DNA 和蛋白质加合物,从而使细胞容易受到长期损伤。正如在吸烟者中所报道的那样,这种长期影响可能导致恶性转化的高易感性。丙烯醛对 DNA 损伤基因的反应也许可以深入了解丙烯醛对 DNA 损伤的原因。本研究的目的是研究丙烯醛在 A549 肺腺癌细胞中对 DNA 损伤反应基因的反应。在 IC50 浓度下用丙烯醛处理显示出 DNA 修复基因的强烈反应,但最终未能阻止细胞发生凋亡。用丙烯醛预处理细胞,然后在没有丙烯醛的新鲜培养基中继续培养相同的细胞,无助于细胞增殖。这些结果表明,暴露于丙烯醛会对 DNA 造成持久的损伤,无论是否有 DNA 修复反应。

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