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组蛋白乙酰化是表观遗传修饰的一种重要方式。肿瘤细胞的组蛋白大部分呈现低乙酰化状态,而组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitor,HDACi)可以增加肿瘤细胞的乙酰化水平,诱导细胞周期阻滞及凋亡。曲古菌素A (trichostatin A,TSA)是组蛋白去乙酰化酶抑制剂的代表药物之一,能够提高肿瘤细胞组蛋白和非组蛋白的乙酰化水平。傅里叶变换红外(Fourier Transform Infrared,FTIR)光谱可以对无染色、无标记的生物样品进行无损检测,具有特征性明显、快速、分辨率高、重复性好等优点,已被广泛用于细胞的微观生物过程的研究。本文利用红外光谱技术结合免疫荧光技术的手段,研究TSA处理细胞后的乙酰化作用效果,发现红外光谱中甲基与亚甲基的伸缩振动强度之比能够表征细胞内的乙酰化水平变化,然后基于红外光谱的分析结果预测了乙酰化状态不同的细胞辐射敏感性的变化。结果表明,乙酰化细胞的辐射损伤效应可以通过甲基与亚甲基的伸缩振动强度之比进行评价,且该比值与细胞的辐射敏感性呈正相关,表明红外光谱技术可以辅助预测细胞的辐射敏感性,并进行细胞表观遗传学特征与辐射效应关系的研究。Histone acetylation is one of important epigenetic modifications, and histone in most of tumor cells shows low acetylation state. However, histone deacetylase inhibitor (HDACi) can correct abnormal acetylation status, induce cell cycle arrest and apoptosis. Trichostatin A (TSA) is one of the representatives of histone deacetylase inhibitors, which can inhibit histone deacetylase, increase the acetylation level of histone and nonhistone in cell. Fourier transform infrared (FTIR) spectroscopy is a powerful analytical tool which can detect nondestructively, quatitatively and quantitatively biological samples without bio-tagging and bio-labeling. FTIR spectroscopy technology has multiple advantages, including finger-print characteristics, rapid analysis, high resolution and good repeatability. Therefore, it has been widely used in the research of biological processes. This work applied FTIR spectroscopy to study the changes in cells treated with TSA, compared the acetylation level according to FTIR intensity ratio of methyl to methylene stretching vibration, and based on the FTIR analysis predicted the radiosensitivity of the cells with different acetylation levels. As a result, we have verified that the damage caused by radiation in acetylated cells can be evaluated by the ratio of methyl and methylene intensity which is positively correlated with cellular radiosensitivity. Therefore, this work demonstrates that FTIR spectroscopy can be useful for the prediction of radiosensitivity and may also open a door for the study of relationship between epigenetics and radiation bio-effects. 相似文献
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用腺病毒重组体(AdCMV p53/GFP)转染经0.5, 1.0和2.0 Gy γ射线辐射处理的前列腺癌细胞[PC 3( nullp53)], 用克隆形成法检测细胞增殖能力, 用流式细胞分析法测定腺病毒重组体转染率和外源性p53蛋白表达。 结果提示, 辐射诱导使腺病毒重组体转染PC 3细胞提高7%—39%。 辐射联合 AdCMV p53 转染组p53表达水平提高18.5%—35.4%。 与单纯 AdCMV p53 转染组和单纯辐射组相比, 辐射联合 AdCMV-p53 转染组细胞存活率分别降低25%—64%和22%—65%。 To determine whether low dose pre irradiation could enhance adenovirus mediated p53 transfer and expression in human prostate adenocarcinoma, the PC 3 cells were pre exposed to γ rays, and then infected with replication deficient adenovirus recombinant vectors, containing human wild type p53 (AdCMV p53) or green fluorescent protein gene (AdCMV GFP) respectively (γ ray irradiation + AdCMV p53 /GFP infection). The exogenous gene transfer and expression were detected by flow cytometric analysis. The GFP transfer frequencies in γ irradiation + AdCMV GFP infection groups were 7%—39% more than those in AdCMV GFP infection groups. The p53 levels in the γ irradiation + AdCMV p53 infection groups were 18.5%—35.4% more than those in AdCMV p53 infection groups (p<0.05),suggesting that low dose (less than or equal to 1.0 Gy) irradiation could significantly promote exogenous p53 transfer and expression in the PC 3 cells. The survival fractions for the γ irradiation + AdCMV p53 infection groups were 25%—64%, 22%—65% less than those for AdCMV p53 infection, or γ irradiation groups, respectively (p<0.05). 相似文献
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重点综述了Siah, HIF, NF-κB和DNA-PK蛋白与肿瘤细胞辐射敏感性关系的最新研究进展。 总结了中国科学院重离子束辐射生物医学重点实验室近几年来在BRCA1等肿瘤细胞辐射敏感性相关蛋白方面的研究工作。 简介了HLET C离子束治疗肿瘤的优点。 展望了此实验室借助兰州重离子研究装置(HIRFL)提供的C离子束研究肿瘤细胞辐射敏感性相关蛋白的目标和方向。 The research progress of tumor cells radiosensitivity associated protein Siah, HIF,NF-κB and DNA-PK are summarized and reviewed. The recent works of our laboratory on tumor cells radiosensitivity associated proteins such as BRCA1 are demonstrated. In the present review, we focused on discussions about the advantages of heavy ion therapy and its possible application in the research of radiosensitivity associated proteins. At the end of this review, we highlighted the future trend and potential targets in the study of tumor cells radiosensitivity associated proteins. 相似文献
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重离子辐射哺乳动物细胞敏感性的分子机理 总被引:14,自引:8,他引:6
研究了用传能线密度125.5keV/μm的12C6+辐照小鼠黑色素瘤、中国仓鼠肺、人的宫颈癌、人的肝癌细胞的敏感性以及DNA双链断裂和DNA双链断裂片段分布,结果表明细胞敏感性与DNA双链断裂之间没有一致的关系,提出了细胞辐射敏感性的一种可能的分子机理,即DNA序列敏感性位点协同DNA双链断裂互补性机理.由此解释了4种细胞系的不同敏感性问题. Four types of cells, melanoma B16, cervical squamous carcinima HeLa, Chinese hamster V79 and hepatoma SMMC 7721, were irradiated by 125.5 keV/μm carbon ions. Celullar sensitivities to irradiation indicated by D50 , DNA double strand break (DSB) and distribution of DSB fragments expressed by molecular weight are studied. The results show that there is not a consistent relationship between cellular sensitivity and DNA DSB induction, a possible molecular mechanism of radiosensitivity which... 相似文献
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本研究旨在探讨羧甲基-β-1,3葡聚糖(CMG)对人肝癌HepG2细胞X射线或12C6+离子束辐射敏感性的影响。首先用CCK-8法检测CMG对HepG2细胞的生长抑制情况,得到半数抑制浓度(IC50)为120.6μg/mL。用浓度为0.1×IC50的CMG预处理HepG2细胞24 h,再给予2 Gy X射线或12C6+离子束辐照(CMG+辐照组);CMG未处理组直接接受2 Gy X射线或12C6+离子束辐照(辐照组)。对比分析辐照组和CMG+辐照组细胞的克隆存活、DNA损伤、凋亡与周期分布、细胞内活性氧(ROS)水平。发现:与X射线辐照组相比,相同剂量的12C6+离子辐照组克隆存活率更小,DNA损伤和周期阻滞更加严重,细胞凋亡率和细胞内ROS水平也更高。与单独X射线或12C6+离子束辐照组相比,CMG+辐照组克隆存活率明显降低,细胞凋亡率随辐照后CMG作用时间的延长而明显增加,CMG使辐照后细胞内ROS维持在一个较高的水平,同时CMG明显加重了单独辐照诱导的DNA损伤和周期阻滞。结果表明,与X射线相比,HepG2细胞对相同剂量的12C6+离子辐射更敏感;CMG可增加HepG2细胞对X射线或12C6+离子辐射的敏感性;CMG可能通过增加受照HepG2细胞内的ROS水平,加剧辐照诱导的DNA损伤,促进辐射诱导细胞凋亡而起到辐射增敏作用。This study aims to investigate the effect of carboxymethy-β-1, 3-glucan (CMG) on the sensitivity of human hepatoma HepG2 cells to X-rays or 12C6+ ions irradiation. First, the inhibitory effect of CMG on the growth of HepG2 cells was detected by CCK-8 assay, and the half maximal inhibitory concentration (IC50) was 120.6 μg/mL. HepG2 cells were pretreated with CMG at a concentration of 0.1×IC50 for 24 h and then irradiated with 2 Gy X-ray or 12C6+ ion beams (CMG + irradiation group). CMG untreated group was directly irradiated by 2 Gy X-rays or 12C6+ ions beam (irradiation group). The clone survival, DNA damage, cell apoptosis, cell cycle distribution, and intracellular reactive oxygen species (ROS) levels in irradiation group and CMG + irradiation group were comparatively analyzed. The results showed that the clone survival rate was lower, DNA damage and cycle arrest were more serious, and the rate of apoptosis and intracellular ROS levels were higher in 12C6+ ions irradiation group than those in the same dose of X-rays irradiation group. Compared with X-rays or 12C6+ ions irradiation group, the clone survival rate of CMG + irradiation group was significantly decreased, and the apoptosis rate significantly increased with the prolongation of CMG treatment post-irradiation; CMG maintained intracellular ROS at a higher level after irradiation, CMG also significantly aggravated radiation-induced DNA damage and cycle arrest. These results indicated that HepG2 cells were more sensitive to 12C6+ ions radiation than those at the same dose of X-rays. CMG increased the sensitivity of HepG2 cells to X-rays or 12C6+ ions irradiation by increasing intracellular ROS level, exacerbating radiation-induced DNA damage and promoting radiation-induced apoptosis in irradiated HepG2 cells. 相似文献
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本研究将FUZZY聚类分析方法首次应用于辐射生物学和植物辐射育种,对普通小麦品种辐射敏感性作了FUZZY聚类分析.供试的小麦品种,按其对γ-射线的辐射敏感性强弱分为极敏感型、敏感型、中间型、迟钝型和极迟钝型五类.这一结果对小麦辐射育种工作中选择适宜的辐照材料、确定最佳的辐照剂量,从而提高辐射诱变效率具有重要的指导意义.研究还表明,采用FUZZY聚类分析对植物的品种辐射敏感性进行分类较其他方法具有更强的可靠性. 相似文献
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Ju Cheol Son Dong Woo Kang Kwang Mo Yang Kang-Yell Choi Tae Gen Son Do Sik Min 《Experimental & molecular medicine》2013,45(8):e38
Radiation and drug resistance remain the major challenges and causes of mortality in the treatment of locally advanced, recurrent and metastatic breast cancer. Dysregulation of phospholipase D (PLD) has been found in several human cancers and is associated with resistance to anticancer drugs. In the present study, we evaluated the effects of PLD inhibition on cell survival, cell death and DNA damage after exposure to ionizing radiation (IR). Combined IR treatment and PLD inhibition led to an increase in the radiation-induced apoptosis of MDA-MB-231 metastatic breast cancer cells. The selective inhibition of PLD1 and PLD2 led to a significant decrease in the IR-induced colony formation of breast cancer cells. Moreover, PLD inhibition suppressed the radiation-induced activation of extracellular signal-regulated kinase and enhanced the radiation-stimulated phosphorylation of the mitogen-activated protein kinases p38 and c-Jun N-terminal kinase. Furthermore, PLD inhibition, in combination with radiation, was very effective at inducing DNA damage, when compared with radiation alone. Taken together, these results suggest that PLD may be a useful target molecule for the enhancement of the radiotherapy effect. 相似文献
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Poly(p‐phenylene) with Poly(ethylene glycol) Chains and Amino Groups as a Functional Platform for Controlled Drug Release and Radiotherapy 下载免费PDF全文
Bahar Guler Huseyin Akbulut Firat Baris Barlas Caner Geyik Dilek Odaci Demirkol Ahmet Murat Senisik Halil Armagan Arican Hakan Coskunol Suna Timur Yusuf Yagci 《Macromolecular bioscience》2016,16(5):730-737
Conventional cancer treatments such as chemotherapy, radiotherapy, or combination of these two result in side effects, which lower the quality of life of the patients. To overcome problems with these methods, altering the drug properties by conjugating them to carrier polymers has emerged. Such polymeric carriers also hold the potential to make tumor cells more sensitive to radiation therapy. Herein, poly(p‐phenylene) (PPP) polymer with poly(ethylene glycol) (PEG) chains and primary amino groups (PPP‐NH2‐g‐PEG) is synthesized and conjugated with anticancer drug Doxorubicin (DOX). pH dependent drug release experiments are performed at pH 5.3 and pH 7.4, respectively. Cell viability studies on human cervix adenocarcinoma cells show that lower doses of DOX inhibit cell proliferation when conjugated with nontoxic doses of PPP‐NH2‐g‐PEG polymer. Additionally, PPP‐NH2‐g‐PEG/Cys/DOX bioconjugate significantly increases radiosensitive properties of DOX. It is possible to use lower doses of DOX when conjugated to PPP‐NH2‐g‐PEG in combination with radiotherapy.
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Fluorescence studies on radiation oxidative damage to membranes with implications to cellular radiosensitivity 总被引:2,自引:0,他引:2
K. P. Mishra 《Journal of Chemical Sciences》2002,114(6):705-711
Radiation oxidative damage to plasma membrane and its consequences to cellular radiosensitivity have received increasing attention
in the past few years. This review gives a brief account of radiation oxidative damage in model and cellular membranes with
particular emphasis on results from our laboratory. Fluorescence and ESR spin probes have been employed to investigate the
structural and functional alterations in membranes after y-irradiation. Changes in the lipid bilayer in irradiated unilamellar
liposomes prepared from egg yolk lecithin (EYL) were measured by using diphenylhexatriene (DPH) as a probe. The observed increase
in DPH polarization and decrease in fluorescence intensity after γ-irradiation of liposomes imply radiation-induced decrease
in bilayer fluidity. Inclusion of cholesterol in liposome was found to protect lipids against radiation damage, possibly by
modulation of bilayer organization e.g. lipid packing. Measurements on dipalmitoyl phosphatidylcholine (DPPC) liposomes loaded
with 6-carboxyfluorescein (CF) showed radiation dose-dependent release of the probe indicating radiation-induced increased
permeability. Changes in plasma membrane permeability of thymocytes were monitored by fluorescein diacetate (FDA) and induced
intracellular reactive oxygen species (ROS) were determined by 2,7-dichlorodihydro fluorescein diacetate (DCH-FDA). Results
suggest a correlation between ROS generation and membrane permeability changes induced by radiation within therapeutic doses
(0-10 Gy). It is concluded that increase in membrane permeability was the result of ROS-mediated oxidative reactions, which
might trigger processes leading to apoptotic cell death after radiation exposure. 相似文献
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