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用 G2 染色体放射敏感性检测法定量评估戊二醛对 MCF7 乳腺癌细胞的放射增敏作用。

The radiosensitizing potential of glutaraldehyde on MCF7 breast cancer cells as quantified by means of the G2-chromosomal radiosensitivity assay.

机构信息

Institute of Radioisotopes & Radiodiagnostic Products, National Center for Scientific Research, NCSR Demokritos Terma Patriarhou Gregoriou & Neapoleos, 153 10 Ag. Paraskevi Attikis, Athens, Greece.

出版信息

Mol Biol Rep. 2012 Jan;39(1):251-7. doi: 10.1007/s11033-011-0733-2. Epub 2011 May 10.

Abstract

Glutaraldehyde (GA) is a high production volume chemical that is very reactive with a wide spectrum of medical, scientific and industrial applications. Concerning the genotoxic and carcinogenic effect of GA, controversial results have been reported, while in humans no studies with positive carcinogenic results for GA have been published. However, our previous study concerning the combined effects of exposure to both GA and ionising radiation (IR) in peripheral blood lymphocytes of healthy donors has shown that non-genotoxic doses of the chemical induces a statistically significant increase in chromosomal radiosensitivity. The lack of information concerning the radiosensitizing potential of GA on cancerous cells triggered us to test the radiosensitizing effect of GA on breast cancer cells (MCF7). For this purpose the G2-chromosomal radiosensitivity assay (G2-assay) was used. The assay involves G2-phase irradiation and quantitation of the chromosomal fragility in the subsequent metaphase. The experimental data show that 48 h exposure to GA, at doses that are not clastogenic to MCF7 breast cancer cells enhances G2-chromosomal radiosensitivity of this cell line. In an effort to evaluate whether the observed increase in GAs-induced G2-chromosomal radiosensitization is linked to GA-induced alterations in the cell cycle and feedback control mechanism, Mitotic Index analysis was performed. The results have shown that such a mechanism cannot be directly related to the observed GA-induced increase in G2-chromosomal radiosensitivity. Since increased G2-chromosomal radiosensitivity has been linked with cancer proneness, the radiosensitizing effect of GA at non-clastogenic doses highlights its potential carcinogenic profile.

摘要

戊二醛(GA)是一种高产量的化学品,具有广泛的医学、科学和工业应用。关于 GA 的遗传毒性和致癌性作用,已经有报道称存在争议结果,而在人类中,尚未发表 GA 具有阳性致癌结果的研究。然而,我们之前关于健康供体外周血淋巴细胞中同时暴露于 GA 和电离辐射(IR)的联合效应的研究表明,该化学物质的非遗传毒性剂量会导致染色体辐射敏感性呈统计学显著增加。缺乏关于 GA 对癌细胞的放射增敏作用的信息促使我们测试 GA 对乳腺癌细胞(MCF7)的放射增敏作用。为此,我们使用了 G2 染色体放射敏感性测定法(G2 测定法)。该测定法涉及 G2 期照射和随后中期染色体脆性的定量。实验数据表明,48 小时暴露于 GA 剂量不会使 MCF7 乳腺癌细胞产生断裂,但会增强该细胞系的 G2 染色体辐射敏感性。为了评估观察到的 GA 诱导的 G2 染色体放射增敏作用是否与 GA 诱导的细胞周期和反馈控制机制改变有关,我们进行了有丝分裂指数分析。结果表明,这种机制不能直接与观察到的 GA 诱导的 G2 染色体放射增敏作用相关。由于增加的 G2 染色体辐射敏感性与癌症易感性有关,因此在非断裂剂量下 GA 的放射增敏作用突出了其潜在的致癌特征。

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