Radon-induced reduced apoptosis in human bronchial epithelial cells with knockdown of mitochondria DNA.
Radon-induced reduced apoptosis in human bronchial epithelial cells with knockdown of mitochondria DNA.
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DOI：
10.1080/15287394.2012.699841
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Tong J
中科院分区：
文献类型：
--
作者：
Li BY;Sun J;Wei H;Cheng YZ;Xue L;Cheng ZH;Wan JM;Wang AQ;Hei TK;Tong J
氡及其子体吸入被认为是诱发肺癌的诱因。为探讨线粒体在氡致癌中的作用，用溴化乙锭(EB)处理人支气管上皮细胞(ρ−+)，建立了部分耗竭线粒体DNA(ρ)细胞系。ρ−细胞的特征表明存在功能障碍的线粒体，因此可能为研究线粒体的作用提供可靠的模型。在气体吸入室中，ρ−和ρ+细胞暴露在由氡源产生的氡气中。结果表明，氡照射后ρ−和ρ+细胞的凋亡率均显著增加。此外，ρ−细胞的凋亡率低于ρ+细胞。进一步发现，氡对线粒体DNA缺失的HBE细胞线粒体膜电位有抑制作用。暴露于氡的ρ−和ρ+细胞产生的活性氧(ROS)明显增加。ρ−细胞周期时相分布与ρ+细胞不同。氡照射后ρ+细胞G2/M期增加，S期减少。在ρ−细胞中，G1、G2/M和S群体与氡暴露的细胞相似。结论：氡诱导的ROS生成、基质金属蛋白酶和细胞周期的改变都归因于细胞凋亡的减少，从而可能触发和促进细胞转化，从而导致癌症的发生。我们的研究表明，利用ρ−基因敲除的线粒体HBE细胞可以作为研究线粒体在致癌疾病中所起作用的可靠模型。
Radon and radon progeny inhalation exposure are recognized to induce lung cancer. To explore the role of mitochondria in radon-induced carcinogenesis in humans, an in vitro partially depleted mitochondrial DNA (mtDNA) cell line (ρ−) was generated by treatment of human bronchial epithelial (HBE) cells (ρ+) with ethidium bromide (EB). The characterization of ρ− cells indicated the presence of dysfunctional mitochondria and might thus serve a reliable model to investigate the role of mitochondria. In a gas inhalation chamber, ρ− and ρ+ cells were exposed to radon gas produced by a radium source. Results showed that apoptosis was significantly increased both in ρ− and ρ+ cells irradiated by radon. Moreover, apoptosis in ρ− cells showed a lower level than in ρ+ cells. Radon was further found to depress mitochondrial membrane potential (MMP) of HBE cells with knock-down mtDNA. Production of reactive oxygen species (ROS) was markedly elevated both in ρ− and ρ+ cells exposed to radon. The distribution of phases of cell cycle was different in ρ− compared to ρ+ cells. Radon-irradiation induced a rise in G2/M and decrease in S phase in ρ+ cells. In ρ− cells, G1, G2/M and S populations remained similar to cells exposed to radon. In conclusion, radon-induced changes in ROS generation, MMP and cell cycle are all attributed to reduction of apoptosis which may trigger and promote cell transformation leading to carcinogenesis. Our study indicates that the use of the ρ− knock-down mtDNA HBE cells may serve as a reliable model to study the role played by mitochondria in carcinogenic diseases.
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影响因子：
8
作者：
Huang, L;Snyder, AR;Morgan, WF
通讯作者：
Morgan, WF
DOI：
10.1080/15287390500260945
发表时间：
2006-04-01
影响因子：
2.6
作者：
Krewski, D;Lubin, JH;Wilcox, HB
通讯作者：
Wilcox, HB
DOI：
10.1196/annals.1354.022
发表时间：
2006-01-01
期刊：
UNDERSTANDING AND MODULATING AGING
影响因子：
--
作者：
Singh, Keshav K.
通讯作者：
Singh, Keshav K.
影响因子：
10.8
作者：
Mathur, A;Hong, Y;Erusalimsky, JD
通讯作者：
Erusalimsky, JD
影响因子：
11.2
作者：
Shidara, Y;Yamagata, K;Ohta, S
通讯作者：
Ohta, S