The synergistic effect of chemical carcinogens enhances Epstein-Barr virus reactivation and tumor progression of nasopharyngeal carcinoma cells.
The synergistic effect of chemical carcinogens enhances Epstein-Barr virus reactivation and tumor progression of nasopharyngeal carcinoma cells.
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DOI：
10.1371/journal.pone.0044810
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chen JY
中科院分区：
文献类型：
--
作者：
Fang CY;Huang SY;Wu CC;Hsu HY;Chou SP;Tsai CH;Chang Y;Takada K;Chen JY
血清流行病学研究表明，EB病毒(EBV)的重新激活与鼻咽癌(NPC)的发生有关。N-亚硝基化合物、苯酚和丁酸盐是从鼻咽癌高危地区采集的食品和草药样本中发现的化学物质。这些化学物质已被报道为鼻咽癌发生的危险因素，但其潜在的机制尚不完全清楚。我们先前已经证明，小剂量N-甲基-N‘-硝基-N-亚硝基(MNNG，0.1µg/ml)与12-O-十四酰佛波醇-13-乙酸酯(TPA)和丁酸钠(SB)在增强携带EBV的鼻咽癌细胞的EBV再激活和基因组不稳定性方面具有协同作用。考虑到鼻咽癌高发区居民可能经常接触这些化学致癌物，阐明化学物质与EBV的关系及其在鼻咽癌发生中的作用是至关重要的。在这项研究中，我们构建了一个细胞培养模型，显示在TPA/SB和MNNG联合治疗后，鼻咽癌细胞中EBV反复激活后，基因组不稳定、肿瘤标志物基因表达的变化和致瘤性增加。用MNNG、TPA/SB或TPA/SB联合MNNG周期性地处理潜伏感染EBV、NA的鼻咽癌细胞和相应的EBV阴性鼻咽癌细胞NPC-TW01。在化学诱导的EB病毒反复激活的情况下，TPA/SB和MNNG联合处理的NA细胞的基因组不稳定程度显著高于单独处理的NA细胞。在反复激活EBV后，NA细胞的Matrigel侵袭力以及在小鼠体内的致瘤性也得到了增强。基因芯片的表达谱分析表明，EBV反复激活后，许多致癌相关基因发生了变化，在细胞系中观察到的几种异常与鼻咽癌病变的变化相对应。这些结果表明，化学致癌物之间的协同作用可以增强EBV的重新激活，并在过度重复激活的情况下，导致癌症标志基因表达的改变，从而促进鼻咽癌的成瘤。
Seroepidemiological studies imply a correlation between Epstein-Barr virus (EBV) reactivation and the development of nasopharyngeal carcinoma (NPC). N-nitroso compounds, phorbols, and butyrates are chemicals found in food and herb samples collected from NPC high-risk areas. These chemicals have been reported to be risk factors contributing to the development of NPC, however, the underlying mechanism is not fully understood. We have demonstrated previously that low dose N-methyl-N’-nitro-N-nitrosoguanidine (MNNG, 0.1 µg/ml) had a synergistic effect with 12-O-tetradecanoylphorbol-13-acetate (TPA) and sodium butyrate (SB) in enhancing EBV reactivation and genome instability in NPC cells harboring EBV. Considering that residents in NPC high-risk areas may contact regularly with these chemical carcinogens, it is vital to elucidate the relation between chemicals and EBV and their contributions to the carcinogenesis of NPC. In this study, we constructed a cell culture model to show that genome instability, alterations of cancer hallmark gene expression, and tumorigenicity were increased after recurrent EBV reactivation in NPC cells following combined treatment of TPA/SB and MNNG. NPC cells latently infected with EBV, NA, and the corresponding EBV-negative cell, NPC-TW01, were periodically treated with MNNG, TPA/SB, or TPA/SB combined with MNNG. With chemically-induced recurrent reactivation of EBV, the degree of genome instability was significantly enhanced in NA cells treated with a combination of TPA/SB and MNNG than those treated individually. The Matrigel invasiveness, as well as the tumorigenicity in mouse, was also enhanced in NA cells after recurrent EBV reactivation. Expression profile analysis by microarray indicates that many carcinogenesis-related genes were altered after recurrent EBV reactivation, and several aberrations observed in cell lines correspond to alterations in NPC lesions. These results indicate that cooperation between chemical carcinogens can enhance the reactivation of EBV and, over recurrent reactivations, lead to alteration of cancer hallmark gene expression with resultant enhancement of tumorigenesis in NPC.
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影响因子：
3.7
作者：
Chang YH;Lee CP;Su MT;Wang JT;Chen JY;Lin SF;Tsai CH;Hsieh MJ;Takada K;Chen MR
通讯作者：
Chen MR
影响因子：
3.8
作者：
Dodd, Lori E.;Sengupta, Srikumar;Hildesheim, Allan
通讯作者：
Hildesheim, Allan
DOI：
10.1006/bbrc.2000.3393
发表时间：
2000-09-07
影响因子：
3.1
作者：
Bahrenberg, G;Brauers, A;Jakse, G
通讯作者：
Jakse, G
影响因子：
12.7
作者：
CHEN, JY;CHEN, CJ;YANG, CS
通讯作者：
YANG, CS
影响因子：
3.8
作者：
Feng, P;Ren, EC;Hu, H
通讯作者：
Hu, H