基于内切酶特异性剪切作用的疾病DNA电化学分析方法研究
|
摘要
随着国民经济和社会的不断发展、生活水平的不断提高,人们对自身健康的要求也越来越高,但各种疾病仍是危害人类健康的重要因素之一,它的发病和死亡率上升己引起人们的普遍关注,对各种疾病进行早期诊断和治疗对于提高疾病患者的生存率具有十分重要的意义。因此,早期诊断和疗效观察方法的研究已成为疾病防治研究领域的重要前沿课题之一。本论文旨在建立某些疾病DNA的电化学检测新方法,为某些疾病的临床诊断和疗效观察提供快速、准确和灵敏的方法。主要研究思路是将设计的探针DNA固定在适合的电极表面,然后将特定的电化学指示剂通过共价键合或特性吸附作用固定到探针DNA上；使探针DNA与具有特定疾病基因特征的DNA片段杂交,再经特异性内切酶作用后,记录指示剂分子电化学信号的变化,从而检测疾病DNA。本论文工作主要以丙型肝炎病毒(HCV)和DNA甲基化引起的恶性疾病基因为研究对象,建立HCV的电化学检测方法,实现DNA甲基化检测、DNA甲基化酶活性分析以及与DNA甲基化相关抗癌药物的筛选。主要内容如下：
1.利用限制性内切酶对特定DNA序列的特异性识别和剪切作用,建立了一种HCV特异性分析和检测的电化学方法。该方法是将电化学指示分子硫堇(Thionine)标记的特定序列DNA探针固定在Au电极表面,与目标cDNA(该目标cDNA与HCV的DNA序列有关)进行杂交,然后经限制性内切酶BamHI剪切。剪切后,电化学指示分子硫堇的电化学响应电流减小或消失,电流减小的幅度(Δi)与杂交的目标cDNA浓度有关,因而可实现HCV的电化学检测与分析。我们对各种可能影响检测的因素进行了详细研究,结果表明,在最佳条件下,Δi与目标cDNA在0.1-2.5μmol/L浓度范围内呈线性关系,最低检测限为0.02μmol/L(S/N=3)。并且,该方法能灵敏地分辨出完全互补和只有一个碱基错配的目标cDNA,具有好的选择性,并且能实现实时监测。
2.在前面的研究基础上,选用氧化还原可逆特性较好的羧基二茂铁(FcA)作为电化学指示分子,研究了所建立方法对HCV的电化学检测作用,目的是进一步提高HCV的检测灵敏度,降低其检测限。该方法是先将特定序列的探针DNA固定在Au电极表面并经电化学指示分子FcA标记,再与目标cDNA(该目标cDNA与HCV的DNA序列有关)进行杂交,然后被限制性内切酶BamHI剪切,根据氧化还原指示分子FcA的微分脉冲伏安(DPV)峰电流的变化(Δi)进行检测。用循环伏安及交流阻抗方法对探针DNA在Au电极表面的固定过程进行了表征,用循环伏安及DPV方法对FcA与探针DNA的作用进行了研究,并且,详细研究了杂交时间、离子强度、温度、溶液pH对探针DNA与目标cDNA杂交的影响,实验结果表明,Δi值与HCV DNA(cDNA)在0.05-4.0μmol/L范围内呈线性关系,最低检测限为(0.5±0.2)nmol/L(S/N=3)。该方法能用于识别只有1个错配碱基的目标cDNA并可用于实际样品中HCV的定量检测,具有简单、灵敏度高、特异性好、可实时监测等优点,理论上,只要简单地改变探针DNA的序列及限制性内切酶的种类,该方法就能用于分析检测其他类型的基因型病毒,从而发展成一种通用的DNA分析方法。
3.HCV基因分型对不同基因亚型病毒特异疫苗的研制及临床治疗药物的筛选等都有着十分重要的意义。我们发展了一种基于限制性内切酶BamHI联合金纳米颗粒(AuNPs)信号放大的HCV型别的电化学检测新方法。该方法是将硫堇-探针DNA固定到电极表面,并与HCV 1b型目标cDNA (244-mer)杂交,再经限制性内切酶BamHI剪切,记录剪切前后硫堇DPV峰电流的变化。结果表明,DPV峰电流(Δi)与目标cDNA在1×10-21-1×10-10mol/L浓度范围内呈线性关系,最低检测限达(3.1±0.8)×10-22 mol/L(S/N=3),与常用的罗氏检测HCV试剂盒方法相比(最低检测限是2.7×10-18mmol/L),检测限低4个数量级。而且,该方法还能用于从HCV 1、HCV1a HCV 1b、HCV 6a型中选择性地分辨出HCV 1b型,因而可用于HCV基因型别的检测。
4.发展了一种能用于DNA甲基化的检测、DNA甲基化转移酶活性的分析以及与DNA甲基化相关抗癌药物筛选的电化学方法。该方法是将FcA与探针DNA的3,端共价键合,与目标cDNA杂交后经甲基转移酶(M. SssI)将CpG序列中的胞嘧啶(C)甲基化,并经限制性内切酶HpaII剪切,未甲基化的DNA在特定位点被剪切,而甲基化的DNA不被剪切,根据FcA电化学信号在剪切前后的变化检测DNA甲基化水平、分析甲基化酶活性。我们还研究了抗癌药物5-氮杂胞嘧啶核苷(5-Aza)和5-氮杂-2'-脱氧胞嘧啶核苷(5-Aza-dC)对甲基转移酶活性的抑制作用,表明该方法可用于评估抗癌药物对DNA甲基化酶的抑制作用,并且可用于相关抗癌药物的筛选。
The aim of this thesis is to develop a electrochemical approach used for detection of hepatitis C virus (HCV), the determination of DNA methylation level, analysis the activity of methyltransferase, and evaluation and screen of the inhibitors of methyltransferase. As a general method of DNA detection, these studies are expected to be applicable to other type of DNA analysis. It has high potential application in molecular diagnostics of disease in clinical environments, and may be helpful for the discovery of anticancer drugs. The main results are as follows:
1. An electrochemical method for detection of oligonucleotides related to HCV sequence based on the site-specific cleavage by BamHI endonuclease is described. Thionine covalently linked to the probe DNA sequence is used as indicator. The thionine-labeled probe DNA was self-assembled on the surface of gold electrode and hybridized with target cDNA (an oligonucleotide related to HCV), then digestion with BamHI endonuclease. Electrochemical assay is performed by monitoring the alteration (△i) of the voltammetric signal of thionine before and after the hybridized DNA is digested by BamHI. Under the optimum condition, the value of△i has a linear relationship with the concentration of target cDNA in the region of 0.1 to 2.5μmol/L with a detection limit of 0.02μmol/L (at S/N=3). The proposed model displays a good selectivity by discriminating one-base mismatched cDNA sequence, and the ability to perform real-time monitoring.
2. Our previous study reported a preliminary study on the detection of HCV based on site-specific DNA cleavage of BamHI endonuclease using thionine-labeled probe. In this chapter, the further characterization and optimization of this new electrochemical sensing approach was continued with ferroceneacetic acid (FcA) as an electroactive label. FcA was selected as a label in this work since ferrocene and its derivatives have been considered as excellent probes in electrochemical DNA assays owing to their redox reversibility and synthetic versatility, the ability to promote the detection performance, and so forth. The method was developed by immobilizing a synthetic probe DNA on the surface of gold electrode via the -SH group at the 5'-terminus of the probe, and conjugating the electroactive label of FcA moiety to the 3'-terminus of the probe via formation of covalent bond between the -NH2 and -COOH groups. The FcA-labeled probe was then hybridized with target cDNA (an oligonucleotide related to HCV) and cleaved by BamHI endonuclease. It was demonstrated that the value of△i has a linear relationship with the concentration of the HCV DNA (cDNA) ranging from 0.05 to 4.0μmol/L, and the detection limit of (0.5±0.2) nmol/L at a signal/noise of 3. Moreover, it was successfully used in distinguishing the complementary sequence from the one-mismatched sequences with stability and reproducibility, and can also be used for detection of HCV in real clinical samples. The developed electrochemical approach, which is based on site-specific DNA cleavage of BamHI endonuclease, not only can qualitative and quantitative detect HCV, but also exhibits the advantages of ease of performance, good specificity and selectivity, and the ability to perform real-time monitoring. The developed protocol can be taken as a general method of DNA detection and is expected to be applicable to other type DNA analysis.
3. This chapter proposes a new strategy for the electrochemical detection of HCV RNA level and identification of HCV 1b genotype based on the site-specific cleavage of BamHI endonuclease combined with gold nanoparticles (AuNPs) signal amplification. A 244-mer cDNA from HCV 1a, HCV 1b, HCV 1, and HCV 6a, respectively, was analyzed using a synthetic 21-mer DNA probe, which has been assembled on the electrode surface via a bifunctional molecule of p-aminobenzoic acid (ABA). The results demonstrated that the developed approach can be used for specifically identification of the HCV 1b genotype and selective and sensitive detection of HCV 1b cDNA (244-mer) with a detection limit as low as (3.1±0.8)×10-22 mol/L (less than 200 molecules). Moreover, the developed method has an ability to discriminate the HCV 1b cDNA sequence from even single-base mismatched DNA sequence, to assay the HCV 1b cDNA level precisely from the mixture of HCV 1, HCV 1b, HCV 1a, and HCV 6a, and to detect HCV in real clinical samples. The protocol has high potential application in molecular diagnostics of HCV in clinical environments.
4. This chapter reports an electrochemical approach for the assay of MTase activity and the detection of DNA methylation of specific CpG sites. This approach is based on the voltammetric response of electroactive label (ferroceneacetic acid, FcA), which was conjugated to the 3'-terminus of the DNA, after the DNA hybrid was methylated by methyltransferase (M. Sssl) and further cleaved by HpaII endonuclease. After digested by Hpall, DNA hybrid was cleaved at specific site and electrochemical signals of FcA were decreased or disappeared. However, the cleavage of the endonuclease is blocked by CpG methylation. Therefore, the voltammetric signal after cleavage is related to the methylation status and MTase activity, which forms the basis of the assay of MTase activity and the determination of DNA methylation. The calibration curve indicates that the linear range of M. SssI assay is from 0.5 to 355 U/mL. The detection range of the developed method is much wider than that of previously reported MTase assays based on colorimetric approaches. The detection limit is estimated to be (0.1±0.02) U/mL at a signal/noise of 3. The validity of our developed method in evaluating and screening the inhibitors of M. Sssl was demonstrated by using 5-azacytidine (5-Aza) and 5-aza-2'-deoxycytidine (5-Aza-dC) as model inhibitors. In addition, This work develops an electrochemical approach for rapid detection of genomic DNA methylation level, assay of methyltransferase activity, and evaluation and screen of the inhibitors of methyltransferase. The screening of the inhibitors of MTase can be achieved based on the developed method and may be help for the discovery of anticancer drugs.
1.利用限制性内切酶对特定DNA序列的特异性识别和剪切作用,建立了一种HCV特异性分析和检测的电化学方法。该方法是将电化学指示分子硫堇(Thionine)标记的特定序列DNA探针固定在Au电极表面,与目标cDNA(该目标cDNA与HCV的DNA序列有关)进行杂交,然后经限制性内切酶BamHI剪切。剪切后,电化学指示分子硫堇的电化学响应电流减小或消失,电流减小的幅度(Δi)与杂交的目标cDNA浓度有关,因而可实现HCV的电化学检测与分析。我们对各种可能影响检测的因素进行了详细研究,结果表明,在最佳条件下,Δi与目标cDNA在0.1-2.5μmol/L浓度范围内呈线性关系,最低检测限为0.02μmol/L(S/N=3)。并且,该方法能灵敏地分辨出完全互补和只有一个碱基错配的目标cDNA,具有好的选择性,并且能实现实时监测。
2.在前面的研究基础上,选用氧化还原可逆特性较好的羧基二茂铁(FcA)作为电化学指示分子,研究了所建立方法对HCV的电化学检测作用,目的是进一步提高HCV的检测灵敏度,降低其检测限。该方法是先将特定序列的探针DNA固定在Au电极表面并经电化学指示分子FcA标记,再与目标cDNA(该目标cDNA与HCV的DNA序列有关)进行杂交,然后被限制性内切酶BamHI剪切,根据氧化还原指示分子FcA的微分脉冲伏安(DPV)峰电流的变化(Δi)进行检测。用循环伏安及交流阻抗方法对探针DNA在Au电极表面的固定过程进行了表征,用循环伏安及DPV方法对FcA与探针DNA的作用进行了研究,并且,详细研究了杂交时间、离子强度、温度、溶液pH对探针DNA与目标cDNA杂交的影响,实验结果表明,Δi值与HCV DNA(cDNA)在0.05-4.0μmol/L范围内呈线性关系,最低检测限为(0.5±0.2)nmol/L(S/N=3)。该方法能用于识别只有1个错配碱基的目标cDNA并可用于实际样品中HCV的定量检测,具有简单、灵敏度高、特异性好、可实时监测等优点,理论上,只要简单地改变探针DNA的序列及限制性内切酶的种类,该方法就能用于分析检测其他类型的基因型病毒,从而发展成一种通用的DNA分析方法。
3.HCV基因分型对不同基因亚型病毒特异疫苗的研制及临床治疗药物的筛选等都有着十分重要的意义。我们发展了一种基于限制性内切酶BamHI联合金纳米颗粒(AuNPs)信号放大的HCV型别的电化学检测新方法。该方法是将硫堇-探针DNA固定到电极表面,并与HCV 1b型目标cDNA (244-mer)杂交,再经限制性内切酶BamHI剪切,记录剪切前后硫堇DPV峰电流的变化。结果表明,DPV峰电流(Δi)与目标cDNA在1×10-21-1×10-10mol/L浓度范围内呈线性关系,最低检测限达(3.1±0.8)×10-22 mol/L(S/N=3),与常用的罗氏检测HCV试剂盒方法相比(最低检测限是2.7×10-18mmol/L),检测限低4个数量级。而且,该方法还能用于从HCV 1、HCV1a HCV 1b、HCV 6a型中选择性地分辨出HCV 1b型,因而可用于HCV基因型别的检测。
4.发展了一种能用于DNA甲基化的检测、DNA甲基化转移酶活性的分析以及与DNA甲基化相关抗癌药物筛选的电化学方法。该方法是将FcA与探针DNA的3,端共价键合,与目标cDNA杂交后经甲基转移酶(M. SssI)将CpG序列中的胞嘧啶(C)甲基化,并经限制性内切酶HpaII剪切,未甲基化的DNA在特定位点被剪切,而甲基化的DNA不被剪切,根据FcA电化学信号在剪切前后的变化检测DNA甲基化水平、分析甲基化酶活性。我们还研究了抗癌药物5-氮杂胞嘧啶核苷(5-Aza)和5-氮杂-2'-脱氧胞嘧啶核苷(5-Aza-dC)对甲基转移酶活性的抑制作用,表明该方法可用于评估抗癌药物对DNA甲基化酶的抑制作用,并且可用于相关抗癌药物的筛选。
The aim of this thesis is to develop a electrochemical approach used for detection of hepatitis C virus (HCV), the determination of DNA methylation level, analysis the activity of methyltransferase, and evaluation and screen of the inhibitors of methyltransferase. As a general method of DNA detection, these studies are expected to be applicable to other type of DNA analysis. It has high potential application in molecular diagnostics of disease in clinical environments, and may be helpful for the discovery of anticancer drugs. The main results are as follows:
1. An electrochemical method for detection of oligonucleotides related to HCV sequence based on the site-specific cleavage by BamHI endonuclease is described. Thionine covalently linked to the probe DNA sequence is used as indicator. The thionine-labeled probe DNA was self-assembled on the surface of gold electrode and hybridized with target cDNA (an oligonucleotide related to HCV), then digestion with BamHI endonuclease. Electrochemical assay is performed by monitoring the alteration (△i) of the voltammetric signal of thionine before and after the hybridized DNA is digested by BamHI. Under the optimum condition, the value of△i has a linear relationship with the concentration of target cDNA in the region of 0.1 to 2.5μmol/L with a detection limit of 0.02μmol/L (at S/N=3). The proposed model displays a good selectivity by discriminating one-base mismatched cDNA sequence, and the ability to perform real-time monitoring.
2. Our previous study reported a preliminary study on the detection of HCV based on site-specific DNA cleavage of BamHI endonuclease using thionine-labeled probe. In this chapter, the further characterization and optimization of this new electrochemical sensing approach was continued with ferroceneacetic acid (FcA) as an electroactive label. FcA was selected as a label in this work since ferrocene and its derivatives have been considered as excellent probes in electrochemical DNA assays owing to their redox reversibility and synthetic versatility, the ability to promote the detection performance, and so forth. The method was developed by immobilizing a synthetic probe DNA on the surface of gold electrode via the -SH group at the 5'-terminus of the probe, and conjugating the electroactive label of FcA moiety to the 3'-terminus of the probe via formation of covalent bond between the -NH2 and -COOH groups. The FcA-labeled probe was then hybridized with target cDNA (an oligonucleotide related to HCV) and cleaved by BamHI endonuclease. It was demonstrated that the value of△i has a linear relationship with the concentration of the HCV DNA (cDNA) ranging from 0.05 to 4.0μmol/L, and the detection limit of (0.5±0.2) nmol/L at a signal/noise of 3. Moreover, it was successfully used in distinguishing the complementary sequence from the one-mismatched sequences with stability and reproducibility, and can also be used for detection of HCV in real clinical samples. The developed electrochemical approach, which is based on site-specific DNA cleavage of BamHI endonuclease, not only can qualitative and quantitative detect HCV, but also exhibits the advantages of ease of performance, good specificity and selectivity, and the ability to perform real-time monitoring. The developed protocol can be taken as a general method of DNA detection and is expected to be applicable to other type DNA analysis.
3. This chapter proposes a new strategy for the electrochemical detection of HCV RNA level and identification of HCV 1b genotype based on the site-specific cleavage of BamHI endonuclease combined with gold nanoparticles (AuNPs) signal amplification. A 244-mer cDNA from HCV 1a, HCV 1b, HCV 1, and HCV 6a, respectively, was analyzed using a synthetic 21-mer DNA probe, which has been assembled on the electrode surface via a bifunctional molecule of p-aminobenzoic acid (ABA). The results demonstrated that the developed approach can be used for specifically identification of the HCV 1b genotype and selective and sensitive detection of HCV 1b cDNA (244-mer) with a detection limit as low as (3.1±0.8)×10-22 mol/L (less than 200 molecules). Moreover, the developed method has an ability to discriminate the HCV 1b cDNA sequence from even single-base mismatched DNA sequence, to assay the HCV 1b cDNA level precisely from the mixture of HCV 1, HCV 1b, HCV 1a, and HCV 6a, and to detect HCV in real clinical samples. The protocol has high potential application in molecular diagnostics of HCV in clinical environments.
4. This chapter reports an electrochemical approach for the assay of MTase activity and the detection of DNA methylation of specific CpG sites. This approach is based on the voltammetric response of electroactive label (ferroceneacetic acid, FcA), which was conjugated to the 3'-terminus of the DNA, after the DNA hybrid was methylated by methyltransferase (M. Sssl) and further cleaved by HpaII endonuclease. After digested by Hpall, DNA hybrid was cleaved at specific site and electrochemical signals of FcA were decreased or disappeared. However, the cleavage of the endonuclease is blocked by CpG methylation. Therefore, the voltammetric signal after cleavage is related to the methylation status and MTase activity, which forms the basis of the assay of MTase activity and the determination of DNA methylation. The calibration curve indicates that the linear range of M. SssI assay is from 0.5 to 355 U/mL. The detection range of the developed method is much wider than that of previously reported MTase assays based on colorimetric approaches. The detection limit is estimated to be (0.1±0.02) U/mL at a signal/noise of 3. The validity of our developed method in evaluating and screening the inhibitors of M. Sssl was demonstrated by using 5-azacytidine (5-Aza) and 5-aza-2'-deoxycytidine (5-Aza-dC) as model inhibitors. In addition, This work develops an electrochemical approach for rapid detection of genomic DNA methylation level, assay of methyltransferase activity, and evaluation and screen of the inhibitors of methyltransferase. The screening of the inhibitors of MTase can be achieved based on the developed method and may be help for the discovery of anticancer drugs.
引文
[1]M. T. Carter, A. J. Bard. Voltammetric studies of the interaction of tris (1, 10-phenanthroline) cobalt (Ⅲ) with DNA. Am. Chem. Soc.,1987,109(24):7528-7531.
[2]M. T. Carter, M. Rodriguez, A. J. Bard. Voltammetric studies of the interaction of metal chelates with DNA/tris-chelated complexes of cobalt (Ⅲ) and iron (Ⅱ) with 1, 10-phenanthroline and 2,2'-bipyridine. Am. Chem. Soc.,1989,111(24):8901-8911.
[3]D. W. Pang, H. D. Abruna. Micromethod for investigation of the interaction between DNA and redox-active molecules. Anal. Chem.,1998,70(15):3162-3169.
[4]Y. D. Zhao, D. W. Pang, Z. L. Wang, J. K. Cheng, Y. P. Qi. Electrochemical characterization of gold electrodes modified with DNA. Electroanal. Chem.,1997, 431(2):203-209.
[5]O. R. Alan, V. D. Rik, M. Estelle. Synthesis of a neodymium-quinolate complex for near-infrared electroluminescence applications. Thin Solid Films,2008,516(15): 5062-5068.
[6]周家宏,杨辉,邢巍,陆天虹.一个制备脱氧核糖核酸修饰电极的简便方法.应用化学,2001,18(7)：575-577.
[7]罗国安,梁琼麟,王义明.生命分析化学展望.药物分析杂志,2004,24(1)：100-105.
[8]王薇,王升富.抗癌药物与DNA作用的化学研究进展.化学通报,2003,5：317-322.
[9]S. Reisberg, L. A. Dang, Q. A. Nguyen. Label-free DNA electrochemical sensor based on a PNA-functionalized conductive polymer. Talanta,2008,76(1):206-210.
[10]E. Palecek, M. Fojta. Detecting DNA hybridization and damage. Anal. Chem.,2001, 73(1):74-83.
[11]K. M. Millan, A. Saraullo, S. R. Mikkelsen. Voltammetric DNA biosensor for cystic fibrosis based on a modified carbon paste electrode. Anal. Chem.,1994,66(18): 2943-2948.
[12]K. Hashimoto, K. Ito, Y. Ishimori. Sequence-specific gene detection with a gold electrode modified with DNA probes and electrochemically active dye. Anal. Chem., 1994,66(21):3830-3833.
[13]L. Q. Ren, X. J. Li, G. S. Li, Z. T. Zhao, B. Sun, F. Sun. Coxsackievirus B3 infection and itsmutation in keshan disease. World Journal of Gastroenterology,2004,10(22): 3299-3302.
[14]M. K. Shigenaga, B. N. Ames. Assays for 8-OhdG:a biomarker of in vivo oxidative DNA damage. Free Radic. Biol. Med.,1991,10(3-4):211-216.
[15]M. Berwick, P. Vineis. Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J. Natl. Cancer Inst.,2000,92(11):874-897.
[16]B. B. Zhou, S. J. Elledge. The DNA damage response:putting check points in perspective. Nature,2000,408(6811):433-439.
[17]G. I. Evan, K. H. Vousden. Proliferation cell cycle and apoptosis in cancer. Nature, 2001,411(6835):342-348.
[18]B. C. Aging, Sex and DNA repair. Academic Press Inc, New York:1991,224-228.
[19]M. Takata, M. S. Sasaki, E. Sonoda, C. Morrison, M. Hashimoto, H. Utsumi, Y. Yamaguchi-Iwai, A. Shinohara, S. Takeda. Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integnty in vertebrate ceils. EMBO J,1998,17:5497-5508.
[20]G. Schwrtsman, M. J. Ratain, G. M. Cragg, J. E. Wong, N. Saijo, D. R. Parkinson, Y. Fujiwara, R. Pazdur, D. J. Newman, R. Dagher, L. Di Leone. Anticancer drug discovery and develement throughout the world. J. Clin. Oncol.,2002,20:47-59.
[21]K. Tae, H. S. Lee, B. J. Park, C. W. Park, K. R. Kim, H. Y. Cho, L. H. Kim, B. L. Park, H. D. Shin. Association of DNA repair gene XRCCI polymorphisms with head and neck cancer in Korean population. Int. J. Cancer,2004,111(5):805-808.
[22]B. Hao, H. Wang, K. Zhou, Y. Li, X. Chen, G. Zhou, Y. Zhu, X. Miao, W. Tan, Q. Wei, D. Lin, F. He. Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma. Cancer Res., 2004,64(12):4378-4384.
[23]W. Zhou, G. Liu, D. P. Miller, S. W. Thurston, L. L. Xu, J. C. Wain, T. J. Lynch, L. Su, D. C. Christiani. Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk. Cancer Epidemiol Biomarkers Prev.,2003,12(4): 359-365.
[24]W. Zhou, G. Liu, D. P. Miller, S. W. Thurston, L. L. Xu, J. C. Wain, T. J. Lynch, L. Su, and D. C. Christiani. Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer. Cancer Res.,2002,62(5): 1377-1381.
[25]S. G. Leng, J. Cheng, Z. F. Pan, C. F. Huang, Y. Niu, Y. F. Dai, B. Li, F. S. He, Y. X. Zheng. Associations between XRCC1 and ERCC2 polymorphisms and DNA damage in peripheral blood lymphocyte among coke oven workers. Biomarkers,2004,9(4-5): 395-406.
[26]J. H. Hocijmakers. Genome maintenance mechanisms for P reventing cancer. Nature, 2001,411(6835):366-374.
[27]M. Goldfield. Some epidemiologic studies of transfusion-associated hepatitis. Infusionstherapie,1974,1(8):645-649.
[28]Q. L. Choo, G. Kuo, A. J. Weiner, L. R. Overby, D. W. Bradley, M. Houghton. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science,1989,244(4902):359-362.
[29]T. Arima, H. Shimomura, T. Nakajima, K. Kanai, H. Nagashima, T. Tsuji. Cloning of hepatitis C virus genomes and their properties. Gastroenterol. Jpn.,1990,25:72-76.
[30]A. Takamizawa, C. Mori, I. Fuke, S. Manabe, S. Murakami, J. Fujita, E. Onishi, T. Andoh, I. Yoshida, H. Okayama. Structure and organization of the hepatitis C virus genome isolated from human carriers. J. Virol.,1991,65(3):1105-1113.
[31]戚中田,杜平.丙型肝炎病毒与丙型肝焱.第1版.上海：上海科学技术出版社,1992.51-64.
[32]G. Randall, C. M. Rice, hepatitis C virus cell culture replication systems:their potential use for the development of antiviral therapies. Curr. Infect. Dis.,2001,14(6): 743-747.
[33]N. Kato. Genome of human hepatitis C virus (HCV):gene organization, sequence diversity, and variation. Microb. Comp. Genomics,2000,5(3):129-151.
[34]R. De Francesco, P. Neddermann, L. Tomei, C. Steinkuhler, P. Gallinari, A. Folgori. Biochemical and immunologic properties of the nonstructural proteins of the hepatitis C virus:implications for development of antiviral agents and vaccines. Semin. Liver Dis.,2000,20(1):69-83.
[35]A. Vario, R. Pistis, S. Boccato, A. Ferrari, A. Alberti. Prevalence and significance of hepatic steatosis in hepatitis C. J. Hepatol.,2003,38(2):179-180.
[36]G. K. K. Lau, H. Zhuang. Top hepatology issue in China. J. Gastroent. Hepatol.,2003, 18:A9.
[37]P. Skladal, C. S. Riccardi, H. Yamanaka, P. I. da Costa. Piezoelectric biosensors for real-time monitoring of hybridization and detection of the hepatitis C virus. J. Virol. Methods,2004,117:145-151.
[38]Q. L. Choo, A. J. Weiner, L. R. Overby, G. Kuo, M. Houghton, D. W. Bradley. Hepatitis C virus:the major causative agent of viral non-A, non-B hepatitis. Br. Med. Bull.,1990,46(2):423-441.
[39]S. L. Flamm. Chronic hepatitis C virus infection. JAMA,2003,289:2413-2417.
[40]R. Shirachi, H. Shiraishi, A. Tateda, K. Kikuchi, N. Ishida. Hepatitis "C" antigen in non-A, non-B post-transfusion hepatitis. Lancet,1978,2:853-856.
[41]A. Tateda, K. Kikuchi, Y. Numazaki, R. Shirachi, N. Ishida. Non-B hepatitis in Japanese recipients of blood transfusions:clinical and serologic studies after the introduction of laboratory screening of donor blood for hepatitis B surface antigen. J. Infect. Dis.,1979,139:511-518.
[42]G. Kuo, Q. L. Choo, H. J. Alter, G. L. Gitnick, A. G. Redeker, R. H. Purcell, T. Miyamura, J. L. Dienstag, M. J. Alter, C. E. Stevens. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science,1989, 244:362-364.
[43]G. J. Kotwal, B. M. Baroudy, I. K. Kuramoto, F. F. McDonald, G. M. Schiff, P. V. Holland, J. B. Zeldis. Detection of acute hepatitis C virus infection by ELISA using a synthetic peptide comprising a structural epitope. Proc. Natl. Acad. Sci. U.S.A.,1992, 89:4486-4489.
[44]杨东亮.丙型肝炎的病毒学检测指标及其临床意义.中华肝脏病杂志.2004,12(2)：104-105.
[45]王乐斌,赵久法.抗-HCV阴性献血员丙肝病毒感染及意义.临床医学.2000,25：442-442.
[46]Centers for Disease Control and Prevention (CDC). Hepatitis C virus transmission from an antibody-negative organ and tissue donor-United States.2000 to 2002. Morb. Mortal. Wkly. Rep.,2003,52:273-274.
[47]M. Willems, H. J. Metselaar, H. W. Tilanus, S. W. Schalm, R. A. de Man. Liver transplantation and hepatitis C. Transpl. Int.,2002,15:61-72.
[48]J. M. Pawlotsky. Use and interpretation of virological tests for hepatitis C. J. Hepatol., 2002,36:S65-S73.
[49]庄辉.重视丙型肝炎的研究.中华肝脏病杂志.2004,12：65-66.
[59]邢文革,郑怀竞.必须提高丙型肝炎病毒实验室检验结果的可信度.中华肝脏病杂志.2004,12：170-171.
[51]王宇明.重视我国丙型肝炎的研究.中华肝脏病杂志.2004,12：106-107.
[52]M. Darius, W. Takaji, K. Tokushige, R. I. Carlson, K. Krawczynski, J. R. Wands. Characterization of three novel monoclonal antibodies against hepatitis C virus core protein. J. Med. Virol.,1996,48:234-241.
[53]郭满盈,李谋深,李保仝,杨毓华.献血者血清中HCV NS3和核心蛋白抗原的检测及临床意义.中国输血杂志,2001,14：78-79.
[54]F. Lunel, P. Veillon, I. Fouchard-Hubert, V. Loustaud-Ratti, A. Abergel, C. Silvain, H. Rifflet, A. Blanchi, X. Causse, Y. Bacq, C. Payan. Fontevraud Study Group. Antiviral effect of ribavirin in early non-responders to interferon monotherapy assessed by kinetics of hepatitis C virus RNA and hepatitis C virus core antigen. J. Hepatol.,2003, 39(5):826-833.
[55]M. Maynard, M. Buti, J. I. Esteban, H. Tillmann, J. Wiegand, M. Manns, M. Martinot, P. Marcellin, P. Berthillon, G R. Picchio, P. Pradat, C. Trepo. Evaluation of the virological response during PEG-IFN/RIB treatment by HCV NAT or total HCV core AG testing leads to similar clinical decisions. J. Hepatol.,2003,38(2):156-156.
[56]G. Ballardini, P. Groff, F. Giostra, R. Francesconi, R. Miniero, S. Ghetti, D. Zauli, F. B. Bianchi. Hepatocellular codistribution of c100, c33, c22, and NS5 hepatitis C virus antigens detected by using immunopurified polyclonal spontaneous human antibodies. J. Hepatol.,1995,21:730-734.
[57]C. Pasquier, L. Bujan, M. Daudin, L. Righi, L. Berges, L. Thauvin, A. Berrebi, P. Massip, J. Puel, J. Izopet. Intermittent detection of hepatitis C virus (HCV) in semen from men with human immunodeficiency virus type 1 (HIV-1) and HCV. J. Med. Virol., 2003,69:344-349.
[58]陈佩兰,李琳,田惠英,陈良标.丙型肝炎患者外周血单个核细胞HCV和Fas抗原检测.军医进修学院学报,2000,21：215-217.
[59]T. Kashiwakuma, A. Hasegawa, T. Kajita, A. Takata, H. Mori, Y. Ohta, E. Tanaka, K. Kiyosawa, T. Tanaka, S. Tanaka, N. Hattori, M. Kohara. Detection of hepatitis C virus specific core protein in serum of patients by a sensitive fluorescence enzyme immunoassay (FEIA). J. Immunol. Methods,1996,190:79-89.
[60]K. Aoyagi, C. Ohue, K. Iida, T. Kimura, E. Tanaka, K. Kiyosawa, S. Yagi. Development of a simple and highly sensitive enzyme immunoassay for hepatitis C virus core antigen. J. Clin. Microbiol.,1999,37:1802-1808.
[61]李保仝,杨毓华,马勇,邵海枫,熊华,赵权,张小卫,武建国.丙型肝炎病毒核心抗原C33的测定.中华实验和临床病毒学杂志,1999,13：68-70.
[62]J. B. Kurtz, E. Boxall, N. Qusir, J. Shirley, D. Coleman, C. Chandler. The diagnostic singnificance of an assay for 'total' hepatitis C core antigen. J. Virol. Methods,2001,96: 127-132.
[63]A. M. Courouce, N. Le Marrec, F. Bouchardeau, A. Razer, M. Maniez, S. Laperche, N. Simon. Efficacy of HCV core antigen detection during the preseroconversion period. Transfusion,2000,40:1198-1202.
[64]S. R. Lee, J. Peterson, P. Niven, C. Bahl, E. Page, R. Deleys, D. Giordano-Schmidt, D. Baggett, G. Green. Efficacy of a hepatitis C virus core antigen enzyme-linked immunosorbent assay for the identification of 'window-phase' blood donations. Vox. Sanguinis,2001,80:19-23.
[65]S. B. Baylin, J. G. Herman. DNA hypermethylation in tumorigenesis:epigetics joins genetics. Trends Genet.,2000,16(4):168-174.
[66]A. Bird. DNA methylation patterns and epigenetic memory. Genes Dev.,2002,16 (1): 6-21.
[67]C. T. Wu, J. R. Morris. Genes, genetics, and epigenetics:A correspondence. Science, 2001,293(5532):1103-1105.
[68]A. P. Bird. CpG-rich islands and the function of DNA methylation. Nature,1986,. 321(6067):209-213.
[69]P. A. Jones, D. Takai. The role of DNA methylation in mammalian epigenetics. Science,2001,293(5532):1068-1070.
[70]Y. Yamada, H. Watanabe, F. Miura, H. Soejima, M. Uchiyama, T. Iwasaka, T. Mukai, Y. Sakaki, T. Ito. A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 21q. Genome Res.,2004,14(2):247-266.
[71]M. S. Greenblatt, W. P. Bennett, M. Hollstein, C. C. Harris. Mutations in the p53 tumor suppressor gene:Clues to cancer etiology and molecular pathogenesis. Cancer Res.,1994,54(18):4855-4878.
[72]S. Kimmins, P. Sassone-Corsi. Chromatin remoding and epigenetic features of germ cells. Nature,2005,434(7033):583-589.
[73]L. S. Dario, M. A. Rosa, E. Mariela, G. Roberto, C. Caterina. Chromatin remodeling agents for cancer therapy. Rev. Recent Clin. Trials,2008,3(3):192-203.
[74]G. Egger, G. N. Liang, A. Aparicio, P. A. Jones. Telomerase activity of sarcoma cell lines and fibroblasts is independent of P53 status. Nature,2004,429(6990):457-463.
[75]A. L. Carvalho, C. Jerenimo, M. M. Kim, R. Henrique, Z. Zhang, M. O. Hoque, S. Chang, M. Brait, C. S. Nayak, W. W. Jiang, Q. Claybourne, Y. Tokumaru, J. Lee, D. Goldenberg, E. Garrett-Mayer, S. Goodman, C. Moon, W. Koch, W. H. Westra, D. Sidransky, J. A. Califano. Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma. Clin. Cancer Res.,2008,14(1):97-107.
[76]A. S. Wilson, B. E. Power, P. L. Molloy. DNA hypomethylation and human diseases. Biochim. Biophys. Acta,2007,1775(1):138-162.
[77]M. Frommer, L. E. McDonald, D. S. Millar, C. M. Collis, F. Watt, G. W. Grigg, P. L. Molloy, C. L. Paul. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc. Natl. Acad. Sci. U.S.A., 1992,89(5):1827-1831.
[78]X. Liu, A. Clements, K. H. Zhao, R. Marmorstein. Structure of the human papillomavirus E7 oncoprotein and its mechanism for inactivation of the retinoblastoma tumor suppressor. J. Biol. Chem.,2006,281(1):578-586.
[79]A. M. Maxam, W. Gilbert. A new method for sequencing DNA. Proc. Natl. Acad. Sci. U.S.A.,1977,74(2):560-564.
[80]J. G. Herman, J. R. Graff, S. Myohanen, B. D. Nelkin, S. B. Baylin. Methylation-specific PCR:a novel PCR assay for methylation status of CpG islands. Proc. Natl. Acad. Sci. U.S.A.,1996,93(18):9821-9826.
[81]K. C. Kuo, R. A. McCune, C. W. Gehrke, R. Midgett, M. Ehrlich. Quantitative reversed-phase high performance liquid chromatographic determination of major and modified deoxyribonucleosides in DNA. Nucl. Acids Res.,1980,8(20):4763-4776.
[82]D. Deng, G. Deng, Y. Lv, J. Zhou, H. Xin. Analysis of the methylation in CpG island by denaturing high-performance liquid chromatography. National Medical Journal of China,2001,80(3):158-161.
[83]P. J. Oefner, G. K. Bonn, C. G. Huber, S. Nathakarnkitkool. Comparative study of capillary zone electrphoresis and high-performance liquid chromatography in the analysis of oligonucleotides and DNA. J. Chromatogr. A,1992,625(2):331-340.
[84]M. F. Fraga, E. Uriol, L. Borja-Diego, M. Berdasco, M. Esteller, M. J. Canal, R. Rodriguez. High-performance capillary electrophoretic method for the quantification of 5-methyl 2-deoxycytidine in genomic DNA:application to plant, animal and human cancer tissues. Electrophoresis,2002,23(11):1677-1681.
[85]张敏,汪国生,陈伟,汪云敏,李向培,阚明,何晓东.系统性红斑狼疮患者基因组DNA甲基化水平的研究.实用医学杂志,2009,25(6)：889-891.
[86]Y. M. Dennis Lo, I. H. N. Wong, J. Zhang, M. S. C. Tein, M. H. L. Ng, N. M. Hjelm. Quantitative analysis of aberrant p16 methylation using real-time quantitative methylation-specific polymerase chain reaction. Cancer Res.,1999,59(16): 3899-3903.
[87]C. A. Eads, K. D. Danenberg, K. Kawakami, L. B. Saltz, C. Blake, D. Shibata, P. V. Danenberg, P. W. Laird. MethyLight:a high-throughput assay to measure DNA methylation. Nucl. Acids Res.,2000,28(8):e32
[88]X. Yang, G. Qiu, S. Ye, X. Ding, Z. Ou, W. Wang, Y. He. Quantitative detection of DNA methylation by fluorescent quantitative real time PCR using SYBR Green I. Chinese J. Lab. Medicine,2007,30(4):433-434.
[89]C. Dabl, P. Guldberg. DNA methylation analysis techniques. Biogerontology,2003, 4(4):233-250.
[90]J. Worm, A. Aggerholm, P. Guldberg. In-tube DNA methylation profiling by fluorescence melting curve analysis. Clin. Chem.,2001,47(7):1183-1189.
[91]G. Clement, J. Benhattar. A methylation sensitive dot blot assay (MS-DBA) for the quantitative analysis of DNA methylation in clinical samples. J. Clin. Pathol.,2005, 58(2):155-158.
[92]F. Feng, H. Z. Wang, L. L. Han, S. Wang. Fluorescent conjugated polyelectrolyte as an indicator for convenient detection of DNA methylation. J. Am. Chem. Soc.,2008, 130(34):11338-11343.
[93]X. R. Duan, L. B. Liu, F. D. Feng, S. Wang. Cationic conjugated polymers for optical detection of DNA methylation, lesions, and single nucleotide polymorphisms. Acc. Chem. Res.,2010,43(2):260-270.
[94]K. Tanaka, K. Tainaka, T. Kamei, A. Okamoto. Direct labeling of 5-methylcytosine and its applications. J. Am. Chem. Soc.,2007,129(17):5612-5620.
[95]D. Kato, N. Sekioka, A. Ueda, R. Kurita, S. Hirono, K. Suzuki, O. Niwa. A nanocarbon film electrode as a platform for exploring DNA methylation. J. Am. Chem. Soc,2008,130(12):3716-3717.
[96]P. Wang, Z. B. Mai, Z. Dai, X. Y. Zou. Investigaton of DNA methylation by direct electrocatalytic oxidation. Chem. Commun.,2010,46(41):7781-7783.
[97]P. Hou, M. J. Ji, C. W. Ge, J. Y. Shen, S. Li, N. Y. He, Z. H. Lu. Detection of methylation of human p16Ink4a gene 5'-CpG islands by electrochemical method coupled with linker-PCR. Nucl. Acids Res.,2003,31(16):e92
[98]S. N. Liu, P. Wu, W. Li, H. Zhang, C. X. Cai. Electrochemical approach for detection of DNA methylation and assay of the methyltrans ferase activity. Chem. Commun., 2011,47,2844-2846.
[99]C. Chen, G. T. Song, J. S. Ren, X, G, Qu. A simple and sensitive colorimetric pH meter based on DNA conformational switch and gold nanoparticle aggregation. Chem. Commun.,2008, (46):6149-6151.
[100]J. Geng, K. G. Qu, J. S. Ren, X. G. Qu. Rapid and efficient screening of Alzheimer's desease β-amyloid inhibitors using label-free gold nanoparticles. Mol. BioSyst.,2010, 6(12):2389-2391.
[101]C. Chen, G. T. Song, X. J. Yang, J. S. Ren, X. G. Qu. The Kudo 5 total elbow replacement in the treatment of the rheumatoid elbow:results at a minimum of ten years. Biochimie,2010,92(10):1416-1421.
[102]X. L. Zhua, Y. X. Liu, J. H. Yang, Z. Q. Liang, G. X. Li. Gold nanoparticle-based colorimetric assay of single-nucleotide polymorphism of triplex DNA. Biosens. Bioelectron.,2010,25(9):2135-2139.
[103]W. Li, Z. L. Liu, H. Lin, Z. Nie, J. H. Chen, X. H. Xu, S. Z. Yao. Label-free colorimetric assay for methyltransferase activity based on a novel methylation-responsive DNAzyme strategy.Anal. Chem.,2010,82(5):1935-1941.
[104]X. Y. Xu, M. S. Han, C. A. Mirkin. A gold-nanoparticle-based real-time colorimetric screening method for endonuclease activity and inhibition. Angew. Chem. Int. Ed., 2007,46(19):3468-3470.
[105]W. Xu, X. J. Xue, T. H. Li, H. Q. Zeng, X. G. Liu. Ultrasensitive and selective colorimetric DNA detection by nicking endonuclease assisted nanoparticle amplification. Angew. Chem. Int. Ed.,2009,48(37):6849-6852.
[106]T. Liu, J. Zhao, D. M. Zhang, G. X. Li. Novel method to detect DNA methylation using gold nanoparticles coupled with enzyme-linkage reactions. Anal. Chem.,2010, 82(1):229-233.
[107]M. L. Gonzalgo, P. A. Jones. Rapid quantitation of methylation differences at specific sites using methylation-sensitive single nucleotide primer extension (Ms-SNuPE). Nucl. Acids Res.,1997,25(12):2529-2531.
[108]A. Bergerat, W. Guschlbauer, G. V. Fazakerley. Allosteric and catalytic binding of S-adenosylmethionine to escherichia coli DNA adenine methyltransferase monitored by 3H NMR. Proc. Natl. Acad. Sci. U.S.A.,1991,88(15):6394-6397.
[109]M. Maekawa, K. Sugano, H. Kashiwabara, M. Ushiama, S. Fujita, M. Yoshimori, T. Kakizoe. DNA methylation analysis using bisulfite treatment and PCR-single strand conformation polymorphism in colorectal cancer showing microsatellite instability. Biochem. Biophys. Res. Commun.,1999,262(3):671-676.
[110]A. Aggerholm, P. Guldberg, M. Hokland, P. Hokland. Extensive intra-and interindividual heterogeneity of p15INK4B methylation in acute myeloid leukemia. Cancer Res.,1999,59(2):436-441.
[111]C. M. Rodriguez Lopez, B. G. Asenjo, A. J. Lioyd, M. J. Wilkinson. Direct detection and quantification of methylation in nucleic acid sequences using high-resolution melting analysis. Anal. Chem.,2010,82(21):9100-9108.
[112]X. L. Wang, Y. L. Song, M. Y. Song, Z. X. Wang, T. Li, H. L. Wang. Fluorescence polarization combined capillary electrophoresis immunoassay for the sensitive detection of genomic DNA methylation. Anal. Chem.,2009,81(19):7885-7891.
[113]W. Nomura, C. F. Barbas. In vivo site-specific DNA methylation with a designed sequence-enabled DNA methylase. J. Am. Chem. Soc.,2007,129(28):8676-8677.
[114]M. Ehrich, J. Turner, P. Gibbs, L. Lipton, M. Giovanneti, C. Cantor, D. van den Boom. Cytosine methylation profiling of cancer cell lines. Proc. Nat. Acad. Sci. U.S.A., 2008,105(12):4844-4849.
[115]J. C. Mathers. Reversal of DNA hypomethylation by folic acid supplements:possible role in colorectal cancer prevention. Gut,2005,54(4):579-581.
[116]J. M. Trasler. Genete inpriting setting dpigenet patterns for the next generation. Reproduction Fertility and Development,2006,18(1-2):63-69.
[117]M. Esteller, P. G. Corn, S. B. Baylin, J. G. Herman. A gene hypermethylation profile of human cancer. Cancer Res.,2001,61(8):3225-3229.
[118]张静,来茂德,陈俭.结直肠癌及结直肠粘膜P16基因5’CpG岛甲基化状态的研究,中华病理学杂志,2000,29(2)：95-98.
[119]R. Henrique, F. R. Ribeiro, D. Fonseca, M. O. Hoque, A. L. Carvalho, V. L. Costa, M. Pinto, J. Oliveira, M. R. Teixeira, D. Sidransky, C. Jeronimo. High promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients. Clin. Cancer Res.,2007,13(20):6122-6129.
[120]M. R. Abbaszadegan, O. Moaven, H. R. Sima, K. Ghafarzadegan, A. A'rabi, M. N. Forghani, H. R. Raziee, A. Mashhadinejad, M. Jafarzadeh, E. Esmaili-Shandiz, E. Dadkhah..P16 promoter hypermethylation:a useful serum marker for early detection of gastric cancer. World J. Gastroenterol.,2008,14(13):2055-2060.
[121]C. B. Wilcox, B. E. Baysal, H. H. Gallion, M. A. Strange, J. A. DeLoia. High resolution methylation analysis of the BRCA1 promoter in ovarian tumors. Cancer Genet. Cytogenet.,2005,159(2):114-122.
[122]Y. L. Choi, S. Y. Kang, Y. K. Shin, J. S. Choi, S. H. Kim, S. J. Lee, D. S. Bae, G. Ahn. Aberrant hypermethylation of RASSF1A promoter in ovarian borderline tumors and carcinomas. Virchows Arch.,2006,448(3):331-336.
[123]M. Widschwendter, G. C. Jiang, C. Woods, H. M. Muller, H. Fiegl, G. Goebel, C. Marth, E. Muller-Holzner, A. G. Zeimet, P. W. Laird, M. Ehrlich. DNA hypomethylation and ovarian cancer biology. Cancer Res.,2004,64(13):4472-4480.
[124]O. El-Maarri, U. Herbiniaux, J. Walter, J. Oldenburg. A rapid, quantitative, non-radioactive bisulfite-SNuPE-IP RP HPLC assay for methylation analysis at specific CpG sites. Nucl. Acids Res.,2002,30(6):e25.
[125]K. Rand, W. J. Qu, T. Ho, S. J. Clark, P. Molloy. Conversion-specific detection of DNA methylation using real-time polymerase chain reaction (ConLight-MSP) to avoid false positives. Methods,2002,27(2):114-120.
[126]M. W. Y. Chan, L. W. Chan, N. L. S. Tang, K. W. Lo, J. H. M. Tong, A. W. H. Chan, H. Y. Cheung, W. S. Wong, P. S. F. Chan, F. M. M. Lai, K. F. To. Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients. Int. J. cancer,2003,104(5):611-616.
[127]J. Huang, X. Zhang, M. Zhang, J. D. Zhu, Y. L. Zhang, Y. Lin, K. S. Wang, X. F. Qi, Q. Zhang, G. Z. Liu, J. Yu, Y. Cui, P. Y. Yang, Z. Q. Wang, Z. G. Han. Up-regulation of DLK1 gene could contribute to human hepatocellular carcinoma. Carcinogenesis,2007, 28(5):1094-1103.
[128]J. D. Zhu. The altered DNA methylation pattern and its implications in liver cancer. Cell Res.,2005,15(4):272-280.
[129]J. Zhu. DNA methylation and tumors diagnosis. Journal of Diagnostics Concepts & Practice,2009,8(1):15-19.
[130]J. D. Zhu. Life expectancy benefits of gastric bypass surgery. J. Hepatobiliary Pancreat. Surg.,2006,13(4):265-273.
[131]J. D. Zhu, X. B. Yao. Use of DNA methylation for cancer detection and molecular classification. J. Biochem. Mol. Biol.,2007,40(2):135-141.
[132]M. F. Paz, M. F. Fraga, S. Avila, M. Z. Guo, M. Pollan, J. G. Herman, M. Esteller. A systematic profile of DNA methylation in human cancer cell lines. Cancer Res.,2003, 63(5):1114-1121.
[133]B. S. Mann, J. R. Johnson, M. H. Cohen, R. Justice, R. Pazdur. FDA approval summary:vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist,2007,12(10):1247-1252.
[134]J. A. Karam, J. H. Fan, J. Stanfield, E. Richer, E. A. Benaim, E. Frenkel, P. Antich, A. I. Sagalowsky, R. P. Mason, J. T. Hsieh. The use of histone deacetylase inhibitor FK228 and DNA hypomethylation agent 5-azacytidine in human bladder cancer therapy. Int. J. Cancer,2007,120(8):1795-1802.
[135]H. Kasai, K. Kawai. DNA methylation at the C-5 position of cytosine by methyl radicals:A possible role for epigenetic change during carcinogenesis by environmental agents. Chem. Res. Toxicol.,2009,22(6):984-989.
[136]P. Siedlecki, R. G. Boy, T. Musch, B. Brueckner, S. Suhai, F. Lyko, P. Zielenkiewicz. Discovery of two novel, small-molecule inhibitors of DNA methylation. J. Med. Chem.,2006,49(2):678-683.
[137]K. Miki, E. Shimizu, S. Yano, K. Tani, S. Sone. Demethylation by 5-aza-2'-deoxycytidine (5-azadC) of p16INK4A gene results in downregulation of vascular endothelial growth factor expression in human lung cancer cell lines. Oncol. Res.,2000,12(8):335-342.
[138]X. Cui, T. Wakai, Y. Shirai, N. Yokoyama, K. Hatakeyama, S. Hirano. Arsenic trioxide inhibits DNA methyltransferase and restores methylation-silenced genes in human liver cancer cells. Hum. Pathol.,2006,37(3):298-311.
[139]K. O. Uhm, E. S. Lee, Y. M. Lee, H. S. Kim, Y. N. Park, S. H. Park. Aberrant promoter CpG islands methylation of tumor suppressor genes in cholangiocarcinoma. Oncol. Res.,2008,17(4):151-157.
[140]N. Fujita, S. Horiike, R. Sugimoto, H. Tanaka, M. Iwasa, Y. Kobayashi, K. Hasegawa, N. Ma, S. Kawanishi, Y. Adachi. Hepatic oxidative DNA damage correlates with iron overload in chronic hepatitis C patients. Free Radical Biol. Med.,2007,42(3): 353-362.
[141]K. Kiyosawa, T. Sodeyama, E. Tanaka, Y. Gibo, K. Yoshizawa, Y. Nakano, S. Furuta, Y. Akahane, K. Nishioka, R. H. Purcell, H. J. Alter. Interrelationship of blood transfusion, nonA, nonB hepatitis and hepatocellula r carcionoma; Analysis by detection of antibody to hepatitis C virus. J. Hepatol.,1990,12:671-675.
[142]H. Le Guillou-Guillemette, F. Lunel-Fabiani. Detection and quantification of serum or plasma HCV RNA:mini review of commercially available assays, in hepatitis C: Methods and Protocols (2nd edn); H. Tang, Ed., Humana Press:Totowa, NJ,2009, Vol. 510, pp.3-14.
[143]W. P. Hofmann, V. Dries, E. Herrmann, B. Gartner, S. Zeuzem, C. Sarrazin. Comparison of transcription mediated amplification (TMA) and reverse transcription polymerase chain reaction (RT-PCR) for detection of hepatitis C virus RNA in liver tissue. J. Clin. Virol.,2005,32:289-293.
[144]E. Engvall, P. Perlmann. Enzyme-linked immunosorbent assay, elisa:Ⅲ. quantitation of specific antibodies by enzyme-labeled anti-immunoglobulin in antigen-coated tubes. J. Immunol.,1972,109:129-135
[145]C. L. van der Poel, H. W. Reesink, J. J. P. van Boven, H. T. M. Cuypers, I. Winkel, P. J. Exel-Oehlers, W. Schaasberg, P. N. Lelie, A. J. Weiner, A. Polito, S. Quan, R. Di Nello, M. Houghton, D. Mulder-Folkerts, A. Leentvaar-Kuypers. Confirmation of hepatitis C virus infection by new four-antigen recombinant immunoblot assay. The lancet,1991,337(8737):317-319.
[146]M. W. Pfaffl. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res.,2001,29(9):e45.
[147]M. Musiani, S. Venturoli, G. Gallinella, M. Zerbini. Qualitative PCR-ELISA protocol for the detection and typing of viral genomes. Nature Protocols,2007,2, 2502-2510.
[148]M. L. Collins, B. Irvine, D. Tyner, E. Fine, C. Zayati, C. Chang, T. Horn, D. Ahle, J. Detmer, L. P. Shen, J. Kolberg, S. Bushnell, M. S. Urdea, D. D. Ho. A branched DNA signal amplification assay for quantification of nucleic acid targets below 100 molecules/ml. Nucleic Acids Research,1997,25(15):2979-2984.
[149]R. S. Lanciotti, A. J. Kerst. Nucleic Acid Sequence-Based Amplification Assays for Rapid Detection of West Nile and St. Louis Encephalitis Viruses. J. Clin. Microbiol., 2001,39(12):4506-4513.
[150]T. Umemura, R. Y. H. Wang, C. Schechterly, J. W. Shih, K. Kiyosawa, H. J. Alter. Quantitative analysis of anti-hepatitis C virus antibody-secreting B cells in patients with chronic hepatitis C. J. Hepatol.,2006,43(1):91-99.
[151]S. Erensoy. Diagnosis of hepatitis C virus (HCV) infection and laboratory monitoring of its therapy. J. Clin. Virol.,2001,21:271-281.
[152]S. C. Lee, A. Antony, N. Lee, J. Leibow, J. Q. Yang, S. Soviero, K. Gutekunst, M. Rosenstraus. Improved version 2.0 qualitative and quantitative AMPLICOR reverse transcription-PCR tests for hepatitis C virus RNA:calibration to international units, enhanced genotype reactivity, and performance characteristics. J. Clin. Microbiol., 2000,38(11):4171-4179.
[153]Y. C. Lin, M. Y. Huang, K. C. Young, T. T. Chang, C. Y. Wu. A rapid micro-polymerase chain reaction system for hepatitis C virus amplicication. Sens. Actuators B,2000,71:2-8.
[154]R. C. Hollingsworth, P. Sillekens, P. Van Deursen, K. R. Neal, W. L. Lrving, Trent HCV Study Group. Serum HCV RNA levels assessed by quantitative NASBA:stability of viral load over time, and lack of correlation with liver disease. J. Hepatol.,1996, 25(3):301-306.
[155]M. Damen, P. Sillekens, H. T. M. Cuypers, I. Frantzen, R. Melsert. Characterization of the quantitative HCV NASBA assay. J. Virol. Methods,1999,82(1):45-54.
[156]A. Guichon, H. Chiaprelli, A. Martinez, C. Rodrigues, A. Trento, C. J. Russi, G. Carballal. Evaluation of a new NASBA assay for the qualitative detection of hepatitis C virus based on the NucliSens Basic Kit reagents. J. Clin. Virol.,2004,29(2):84-91.
[157]P. M. Richalet-Secordel, F. Poisson, M. H. V. van Regenmortel. Uses of biosensor technology in the development of probes for viral diagnosis. Clin. Diagn. Virol.,1996, 5:111-119.
[158]D. OiMeara, Z. B. Yun, A. Sonnerborg, O. Weiland, J. Lundeberg. Cooperative oligonucleotides mediating direct capture of hepatitis C virus RNA from serum. J. Clin. Microbiol.,1998,36(9):2454-2459.
[159]J. Griffin, A. K. Singh, D. Senapati, E. Lee, K. Gaylor, J. Jones-Boone, P. C. Ray. Sequence specific HCV-RNA quantification using size dependent nonlinear optical properties of gold nanoparticles. Small,2009,5(7):839-845.
[160]G. Bildan, M. Billon, T. Livache, G. Mathis, A. Roget, L. M. Torres- Rodriguez. Conducting polymers as a link between biomolecules and microelectronics. Synth. Met., 1999,102:1363-1365.
[161]C. S. Riccardi, K. Dahmouche, C. V. Santilli, P. I. da Costa, H. Yamanaka. Immobilization of streptavidin in sol-gel films:application on the diagnosis of hepatitis C virus. Talanta,2006,70(3):637-643.
[162]C. S. Riccardi, C. Kranz, J. Kowalik, H.Yamanaka, B. Mizaikoff, M. Josowicz. Label-free DNA detection of hepatitis C virus based on modified conducting polypyrrole films at microelectrodes and atomic force microscopy tip-integrated electrodes. Anal. Chem.,2008,80(1):237-245.
[163]A. E. Radi, J. L. A. Sanchez, E. Baldrich, C. K. O'Sullivan. Reagentless, reusable, ultrasensitive electrochemical molecular beacon aptasensor. J. Am. Chem. Soc.,2006, 128(1):117-124.
[164]Y. Zhang, Y. Wang, H. Wang, J. H. Jiang, G L. Shen, R. Q. Yu, J. H. Li. Based on the proximity-dependent surface hybridization assay. Anal. Chem.,2009,81(5): 1982-1987.
[165]Z. Fang, S. O. Kelley. Direct electrocatalytic mRNA detection using PNA-nanowire sensors. Anal. Chem.,2009,81(2):612-617.
[166]X. Zhang, K. Jiao, S. Liu, Y. W. Hu. Readily reusable electrochemical DNA hybridization biosensor based on the interaction of DNA with single-walled carbon nanotubes. Anal. Chem.,2009,81(15):6006-6012.
[167]J. S. Swensen, Y. Xiao, B. S. Ferguson, A. Lubin, R. Lai, A. J Heeger, K. W. Plaxco, H. T. Soh. Continuous, real-time monitoring of cocaine in undiluted blood serum via a microfluidic, electrochemical aptamer-based sensor. J. Am. Chem. Soc.,2009,131(12): 4262-4266.
[168]K. J. Cash, A. J. Heeger, K. W. Plaxco, Y. Xiao. Optimization of a reusable, DNA pseudoknot-based electrochemical sensor for sequence-specific DNA detection in blood serum. Anal. Chem.,2009,81(2):656-661.
[169]B. Li, Y. Du, H. Wei, S. Dong. Unmodified gold nanoparticles as a colorimetric probe for potassium DNA aptamers. Chem. Commun.,2007:3780-3782.
[170]J. Yuan, W. Guo, X. Yang, E. Wang. Anticancer drug-DNA interactions measured using a photoinduced electron-transfer mechanism based on luminescent quantum dots. Anal. Chem.,2009,81(1):362-368.
[171]H. X. Ju, Y. K. Ye, Y. L. Zhu. Electrochemical study of interaction between nile blue and immobilized single- or double-stranded DNA and its application for cDNA recognition. Electrochim. Acta,2005,50(6):1361-1367.
[172]C. Yao, T. Zhu, J. Tang, R. Wu, Q. Chen, M. Chen, B. Zhang, J. Huang, W. Fu,. Hybridization assay of hepatiis B virus by QCM peptide nucleic acid. Biosens. Bioelectron.,2008,23(6):879-885.
[173]H. T. Zhao, H. X. Ju. Biosensor for hepatitis B virus DNA PCR production and electrochemical study of the interaction of di (2,2'-bipyridine) osmium (Ⅲ) with DNA. Electroanalysis,2004,16(19):1642-1646.
[174]M. Kobayashi, K. B. Takashi, M. Saito, S. Kaji, M. Oomura. Electrochemical DNA quantification based on aggregation induced by Hoechst 33258. Electrochem. Commun.,2004,6(4):337-343.
[175]T. K. Ye, J. H. Zhao, F. Yan, Y. L. Zhu, H. X. Ju. Electrochemical behavior and detection of hepatitis B virus DNA PCR production at gold electrode, Biosens. Bioelectron.,2003,18(12):1501-1508.
[176]H. X. Ju, Y. K. Ye, J. H. Zhao, Y. L. Zhu. Hybridization biosensor using di (2, 2'-bipyridine) osmium (Ⅲ) as electrochemical indicator for detection of polymerase chain reaction product of hepatitis B virus DNA. Anal. Biochem.,2003,313:255-261.
[177]B. Meric, K. Kerman, D. Ozkan, A. Erdem, M. Ozsoz. Electrochemical DNA biosensor for the detection of TT and Hepatitis B virus from PCR amplified real samples by using Methylene Blue. Talanta,2002,56(5):837-846.
[178]D. K. Xu, K. Huang, Z. H. Liu, L. Ma. Microfabricated disposable DNA sensor based on enzymatic amplfication electrochemical detection. Electroanalysis,2001, 13(10):882-887.
[179]G. Nardone, J. George, J. G Chirikjian. Differences in the kinetic properties of BamHI endonuclease and methylase with linear DNA substrates. J. Biol. Chem.,1986, 261(26):12128-12133.
[180]S. Krishnan, E. G. Hvastkovs, B. Bajrami, I. Jansson, J. B. Schenkman, J. F. Rusling. Dehydroacetic acid and its derivatives in organic synthesis:synthesis of some new 2-substituted-4-(5-bromo-4-hydroxy-6-methyl-2H-pyran-2-one-3-y1) thiazoles. Chem. Commun.,2007:1713-1715.
[191]Y. Jin, W. Lu, J. Hu, X. Yao, J. H. Li. Site-specific DNA cleavage by EcoRI endounclease real-time probed by ferrocene capped gold nanoparticles. Electrochem. Commun.,2007,9(5):1086-1090.
[182]G Piperberg, O. I. Wilner, O. Yehezkeli, R. Tel-Vered, I. Willner. Control of bioelectrocatalytic transformations on DNA scaffolds. J. Am. Chem. Soc.,2009, 131(25):8724-8725.
[183]F. Ricci, A. J. Bonham, A. C. Mason, N. O. Reich, K. W. Plaxco. Reagentless, electrochemical approach for the specific detection of double- and single-stranded DNA binding proteins. Anal. Chem.,2009,81(4):1608-1614.
[184]M. Fojta, T. Kubicarova, E. Paleaek. Cleavage of supercoiled DNA by deoxyribonuclease I in solution and at the electrode surface. Electroanalysis,1999, 11(14):1005-1012.
[185]Z. Dai, J. Chen, F. Yan, H. Ju, Electrochemical sensor for immunoassay of carcinoembryonic antigen based on thionine monolayer modified gold electrode. Cancer Detection and Prevention,2005,29 (3):233-240.
[186]D. OiMeara, Z. B. Yun, A. Sonnerborg O. Weiland, J. Lundeberg. Cooperative oligonucleotides mediating direct capture of hepatitis C virus RNA from serum. J. Clin. Microbiol.,1998,36(9):2454-2459.
[187]J. Griffin, A. K. Singh, D. Senapati, E. Lee, K. Gaylor, J. Jones-Boone, P. C. Ray. Sequence specific HCV-RNA quantification using size dependent nonlinear optical properties of gold nanoparticles. Small,2009,5(7):839-845.
[188]H. A. Kozlowska, B. E. Conway, A. Hamelin, L. J. Stoicoviciu. Elementary steps of electrochemical oxidation of single-crystal planes of Au Part Ⅱ. A chemical and structural basis of oxidation of the (Ⅲ) plane. J. Electroanal. Chem.,1987,228(1): 429-453.
[189]R. Szamocki, A. Velichko, C. Holzapfel, A. Lasagni, F. Miicklich, S. Ravaine, A. Kuhn, R. Hempelmann. Macroporous ultramicroelectrodes for improved electroanalytical measurements. Anal. Chem.,2007,79(2):533-539.
[190]H. Qian, L. He. Surface-initiated activators generated by electron transfer for atom transfer radical polymerization in detection of DNA point mutation. Anal. Chem.,2009, 81(11):4536-4542.
[191]R. Lao, S. Song, H. Wu, L. Wang, Z. Zhang, L. He, C. Fan. Electrochemical interrogation of DNA monolayers on gold surfaces. Anal. Chem.,2005,77(19): 6475-6480.
[192]A. B. Steel, T. M. Herne, M. J. Tarlov. Electrochemical quantitation of DNA immobilized on gold. Anal. Chem.,1998,70(22):4670-4677.
[193]X. Luo, T. M. H. Lee, I. M. Hsing. Immobilization-free sequence-specific electrochemical detection of DNA using ferrocene-labeled peptide nucleic acid. Anal. Chem.,2008,80(19):7341-7346.
[194]B. Hinsch, M. R. Kula. Physical and kinetic properties of the site specific endonuclease BamHI from Bacillus amylolique-faciens. Nucleic Acids Res.,1980,8(3): 623-633.
[195]L. E. Englerl, P. Sapienzal, L. F. Dorner, R. Kucera, I. Schildkraut, L. Jen-Jacobson. The energetics of the interaction of BamHI endonuclease with its recognition site GGATCC. J. Mol. Bioi.,2001,307:619-636.
[196]A. J. Bard, L. R. Faulkner, Electrochemical Methods:Fundamentals and Applications (2nd edn), John Wiley & Sons:New York,2001.
[197]H. Zhao, H. Ju. Multilayer membranes for glucose biosensing via layer-by-layer assembly of multiwall carbon nanotubes and glucose oxidase, Anal. Biochem.,2006, 350:138-144.
[198]Y. Yin, P. Wu, Y. Lu, P. Du, Y. Shi, C. X. Cai. Immobilization and direct electrochemistry of cytochrome c at a single-walled carbon nanotube-modified electrode, J. Solid State Electrochem.,2007,11:390-397.
[199]M. Wang, Y. Shen, Y. Liu, T. Wang, F. Zhao, B. Liu, S. Dong. Direct electrochemistry of microperoxidase 11 using carbon nanotube modified electrodes J. Electroanal. Chem.,2005,578:121-127.
[200]F. Patolsky, Y. Weizmann, I. Willner. Redox-active nucleic-acid replica for the amplified bioelectrocatalytic detection of viral DNA. J. Am. Chem. Soc.,2002,124(5): 770-772.
[201]J. Wang, J. Li, A. J. Baca, J. Hu, F. Zhou, W. Yan, D. W. Pang. Amplified voltammetric detection of DNA hybridization via oxidation of ferrocene caps on gold nanoparticle/streptavidin conjugates. Anal. Chem.,2003,75(15):3941-3945.
[202]J. Liu, S. Tian, L. Tiefenauer, P. E. Nielson, W. Knoll. Simultaneously amplified electrochemical and surface plasmon resonce optical detection of DNA hybridization based on ferrocene-streptavidin conjugates. Anal. Chem.,2005,77(9):2756-2761.
[203]A. S. Georgopoulou, D. M. P. Mingos, A. J. P. White, D. J. Williams, B. R. Horrocks, A. Houlton. Bifunctional ferrocene derivatives for molecular recognition of DNA duplexes. J. Chem. Soc., Dalton Trans.,2000:2969-2974.
[204]A. Anne, A. Bouhardon, J. Moiroux.3'-ferrocene-labeled oligonucleotide chains end-tethered to gold electrode surfaces:Novel model systems for exploring flexibility of short DNA using cyclic voltammetry. J. Am. Chem. Soc.,2003,125(5):1112-1113.
[205]E. Laviron. The use of linear potential sweep voltammetry and of a.c. voltammetry for the study of the surface electrochemical reaction of strongly adsorbed systems and of redox modified electrodes. J. Electroanal. Chem.,1979,100(1-2):263-270.
[206]K. Uosaki, Y. Sato, H. Kita. Electrochemical characteristics of a gold electrode modified with a self-assembled monolayer of ferrocenylalkanethiols. Langmuir,1991, 7(7):1510-1514.
[207]C. Fan, K. W. Plaxco, A. J. Heeger. Electrochemical interrogation of conformational changes as a reagentless method for the sequence-specific detection of DNA. Proc. Natl. Acad. Sci. U.S.A.,2003,100(16):9134-9137.
[208]W. C. Liao, J. Ho. Attomole DNA electrochemical sensor for the detection of escherichia coli O157. Anal. Chem.,2009,81(7):2470-2476.
[209]M. A. Joyce, D. L. Tyrrell. The cell biology of hepatitis C virus. Microb. Infect., 2010,14:263-271.
[210]M. A. Joyce, K. A. Walters, S. E. Lamb, M. M. Yeh, L. F. Zhu, N. Kneteman, J. S. Doyle, M. G. Katze, D. L. Tyrrell. HCV induces oxidative and ER stress, and sensitizes infected cells to apoptosis in SCID/Alb-uPA mice. PloS Pathog.,2009,5(2):e1000291.
[211]J. R. Thomas, P. J. Hergenrother. Targeting RNA with small molecules. Chem. Rev., 2008,108(4):1171-1224.
[212]H. Huang, Y. Chen, J. Ye. Inhibition of hepatitis C virus replication by peroxidation of arachidonate and restoration by vitamin E. Proc. Natl. Acad. Sci. U.S.A.,2007, 104(47):18666-18670.
[213]S. N. Liu, Y. J. Hu, J. Jin, H. Zhang, C. X. Cai. Electrochemical detection of hepatitis C virus based on site-specific DNA cleavage of BamHI endonuclease. Chem. Commun.,2009,1635-1637.
[214]S. N. Liu, Q. Wang, D. X. Chen, J. Jin, Y. J. Hu, P. Wu, H. Zhang, C. X. Cai. Electrochemical approach for the specific detection of hepatitis C virus based on site-specific DNA cleavage of BamHI endonuclease. Anal. Methods,2009,2:135-142.
[215]N. A. Antonishyn, V. M. Ast, R. R. McDonald, R. K. Chaudhary, L. Lin, A. P. Andonov, G. B. Horsman. Rapid genotyping of hepatitis C virus by primer-specific extension analysis. J. Clin. Microbiol.,2005,43(10):5158-5163.
[216]M. D. William-Carey, W. Carey. Tests and screening strategies for the diagnosis of hepatitis C. Clin. J. Med.,2003,70:S7-S13.
[217]R. Zhang, S. C. Du, Y. Tian. Regional distribution of mutants with BamHI site of hepatitis C virus genotype 1b 5' noncoding region. China J. Modern Med.,2005,15: 3082-3084.
[218]K. C. Grabar, R. G. Freeman, M. B. Hommer, M. J. Natan. Preparation and characterization of Au colloid monolayers. Anal. Chem.,1995,67(4):735-743.
[219]L. Zhang, X. Jiang. Attachment of gold nanoparticles to glassy carbon electrode and its application for the voltammetric resolution of ascorbic acid and dopamine. J. Electroanal. Chem.,2005,583(2):292-299.
[220]A. Hamelin. Cyclic voltammetry at gold single-crystal surfaces. Part 1. Behaviour at low-index faces. J. Electroanal. Chem.,1996,407(1-2):1-11.
[221]H. Park, S. B. Lee, K. Kim, M. S. Kim. Surface-enhanced Raman scattering of p-aminobenzoic acid at Ag electrode. J. Phys. Chem.,1990,94(19):7576-7580.
[222]D. Zeisel, B. Dutoit, V. Deckert, T. Roth. Optical spectroscopy and laser desorption on a nanometer scale. Anal. Chem.,1997,69(4):749-754.
[223]M. J. Gong, T. Han, C. X. Cai, T. H. Lu, J. Y. Du. Fabrication and characterization of DNA-thionine-carbon nanotubes nanocomposites. J. Electroanal. Chem.,2008, 623(1):8-14.
[224]P. Qiu, X. Y. Cai, L. Wang, J. R. Greene, B. Malcolm. Colony shape as a genetic trait in the pattern-forming bacillus mycoides. BMC Microbiol.,2002,2:1471-2180.
[225]A. Grakoui, D. W. McCourt, C. Wychowski, S. M. Feinstone, C. M. Rice. Characterization of the hepatitis C virus-encoded serine proteinase:determination of proteinase-dependent polyprotein cleavage sites. J. Virol.,1993,67(5):2832-2843.
[226]B. Weinhold. Epigenetics:the science of change. Environ. Health Perspect.,2006, 114:A160-A167.
[227]J. S. Choy, S. Wei, J. Y. Lee, S. Tan, S. Chu, T. H. Lee. DNA methylation increases nucleosome compaction and rigidity. J. Am. Chem. Soc.,2010,132(6):1782-1783.
[228]E. Li, C. Beard, R. Jaenisch. Role for DNA methylation in genomic imprinting. Nature,1993,366(6453):362-365.
[229]E. Heard, P. Clerc, P. Avner. X-chromosome inactivation in mammals. Annu. Rev. Genet.,1997,31:571-610.
[230]W. Reik, F. Santos, W. Dean. Mammalian epigenomics:reprogramming the genome for development and therapy. Theriogenology,2003,59(1):21-32.
[231]C. P. Walsh, J. R. Chaillet, T. H. Bestor. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat. Genet.,1998,20:116-117.
[232]R. Z. Chen, U. Pettersson, C. Beard, L. Jackson-Grusby, R. Jaenisch. DNA hypomethylation leads to elevated mutation rates. Nature,1998,395(6697):89-93.
[233]A. P. Bird, A. P. Wolffe. Methylation-induced repression belts, braces, and chromatin. Cell,1999,99(5):451-454.
[234]J. Kim, A. Kollhoff, A. Bergmann. Methylation-sensitive binding of transcription factor YY1 to an insulator sequence within the paternally expressed imprinted gene, Peg3. Hum. Mol. Genet.,2003,12(3):233-245.
[235]K. D. Roberts. DNA methylation, methyltransferases and cancer. Oncogene,2001, 20(24):3139-3155.
[236]V. Colot, J. L. Rossignol. Eukaryotic DNA methylation as an evolutionary device. Bioessays,1999,21(5):402-411.
[237]S. B. tephen, J. G. Herman. DNA hypermethylation in tumorigenesis. Trends Genet., 2000,16(4):168-174.
[238]B. Brueckner, F. Lyko. DNA methyltransferase inhibitors:old and new drugs for an epigenetic cancer therapy. Trends Pharmacol. Sci.,2004,25:551-554.
[239]R. J. Klose, A. P. Bird. Genomic DNA methylation:the mark and its mediators. Trends Biochem. Sci.,2006,31:89-96.
[240]P. A. Jones, Baylin, S. B. The fundamental role of epigenetic events in cancer, Nat. Rev. Genet.,2002,3:415-428.
[241]M. Esteller. CpG island hypermethylation and tumor suppressor genes:a booming present, a brighter future. Oncogene,2002,21(35):5427-5440.
[242]J. R. Poeter, C. I. Stains, D. J. Segal, I. Ghosh. Split β-lactamase sensor for the sequence-specific detection of DNA methylation. Anal. Chem.,2007,79(17): 6702-6708.
[243]F. Lyko, B. H. Ramsahoye, R. Jaenisch. Development:DNA methylation in drosophila melanogaster. Nature,2000,408:538-540.
[244]G. P. Pfeifer, S. D. Steigerwald, P. R. Mueller, B. Wold, A. D. Riggs. Genomic sequencing and methylation analysis by ligation mediated PCR, Science,1989,246: 810-813.
[245]I. Hatada, Y. Hayashizaki, S. Hirotsune, H. Komatsubara, T. A. Mukai. A genomic scanning method for higher organisms using restriction sites as landmarks. Proc. Natl. Acad. Sci. U.S.A.,1991,88(21):9523-9527.
[246]X. Duan, L. Liu, F. Feng, S. Wang. Cationic conjugated polymers for optical detection of DNA methylation, Acc. Chem. Res.,2010,43:260-270.
[247]X. Wang, Y. Song, M. Song, Z Wang. Fluorescence polarization combined capillary electrophoresis immunoassay for the sensitive detection of genomic DNA methylation. Anal. Chem.,2009,81(19):7885-7891.
[248]J. Li, H. Yan, K. Wang, W. Tan, X. Zhou. Hairpin fluorescence DNA probe for real-time monitoring of DNA methylation. Anal. Chem.,2007,79(3):1050-1056.
[249]G. Song, C. Chen, J. Ren, X. Qu. A simple, universal colorimetric assay for endonuclease/methyltransferase activity and inhibition based on an enzyme-responsive nanoparticle system. ACS Nano.,2009,3(5):1183-1189.
[250]M. F. Fraga, R. Rodriguez, M. J. Canal. Rapid quantification of DNA methylation by high performance capillary electrophoresis. Electrophoresis,2000,21(14):2990-2994.
[251]S. Friso, S. W. Choi, G. G. Dolnikowski, J. Selhub. A method to assess genomic DNA methylation using high-performance liquid chromatography/electrospray ionization mass spectrometry. Anal. Chem.,2002,74(17):4526-4531.
[252]H. Angerstein-Kozlowska, B. E. Conway, A. Hamelin, L. Stoicoviciu. Elementary steps of electrochemical oxidation of single-crystal planes of Au part Ⅱ. A chemical and structural basis of oxidation of the (Ⅲ) plane. J. Electroanal. Chem.,1987,228: 429-453.
[253]Y. L. Zhang, Y. Wang, H. B. Wang, J. H. Jiang, G. L. Shen, R. Q. Yu, J. H. Li. Based on the proximity-dependent surface hybridization assay. Anal. Chem.,2009,81: 1982-1987.
[254]J. K. Christman.5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation:implications for cancer therapy. Oncogene,2002,21:5483-5495.
[2]M. T. Carter, M. Rodriguez, A. J. Bard. Voltammetric studies of the interaction of metal chelates with DNA/tris-chelated complexes of cobalt (Ⅲ) and iron (Ⅱ) with 1, 10-phenanthroline and 2,2'-bipyridine. Am. Chem. Soc.,1989,111(24):8901-8911.
[3]D. W. Pang, H. D. Abruna. Micromethod for investigation of the interaction between DNA and redox-active molecules. Anal. Chem.,1998,70(15):3162-3169.
[4]Y. D. Zhao, D. W. Pang, Z. L. Wang, J. K. Cheng, Y. P. Qi. Electrochemical characterization of gold electrodes modified with DNA. Electroanal. Chem.,1997, 431(2):203-209.
[5]O. R. Alan, V. D. Rik, M. Estelle. Synthesis of a neodymium-quinolate complex for near-infrared electroluminescence applications. Thin Solid Films,2008,516(15): 5062-5068.
[6]周家宏,杨辉,邢巍,陆天虹.一个制备脱氧核糖核酸修饰电极的简便方法.应用化学,2001,18(7)：575-577.
[7]罗国安,梁琼麟,王义明.生命分析化学展望.药物分析杂志,2004,24(1)：100-105.
[8]王薇,王升富.抗癌药物与DNA作用的化学研究进展.化学通报,2003,5：317-322.
[9]S. Reisberg, L. A. Dang, Q. A. Nguyen. Label-free DNA electrochemical sensor based on a PNA-functionalized conductive polymer. Talanta,2008,76(1):206-210.
[10]E. Palecek, M. Fojta. Detecting DNA hybridization and damage. Anal. Chem.,2001, 73(1):74-83.
[11]K. M. Millan, A. Saraullo, S. R. Mikkelsen. Voltammetric DNA biosensor for cystic fibrosis based on a modified carbon paste electrode. Anal. Chem.,1994,66(18): 2943-2948.
[12]K. Hashimoto, K. Ito, Y. Ishimori. Sequence-specific gene detection with a gold electrode modified with DNA probes and electrochemically active dye. Anal. Chem., 1994,66(21):3830-3833.
[13]L. Q. Ren, X. J. Li, G. S. Li, Z. T. Zhao, B. Sun, F. Sun. Coxsackievirus B3 infection and itsmutation in keshan disease. World Journal of Gastroenterology,2004,10(22): 3299-3302.
[14]M. K. Shigenaga, B. N. Ames. Assays for 8-OhdG:a biomarker of in vivo oxidative DNA damage. Free Radic. Biol. Med.,1991,10(3-4):211-216.
[15]M. Berwick, P. Vineis. Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J. Natl. Cancer Inst.,2000,92(11):874-897.
[16]B. B. Zhou, S. J. Elledge. The DNA damage response:putting check points in perspective. Nature,2000,408(6811):433-439.
[17]G. I. Evan, K. H. Vousden. Proliferation cell cycle and apoptosis in cancer. Nature, 2001,411(6835):342-348.
[18]B. C. Aging, Sex and DNA repair. Academic Press Inc, New York:1991,224-228.
[19]M. Takata, M. S. Sasaki, E. Sonoda, C. Morrison, M. Hashimoto, H. Utsumi, Y. Yamaguchi-Iwai, A. Shinohara, S. Takeda. Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integnty in vertebrate ceils. EMBO J,1998,17:5497-5508.
[20]G. Schwrtsman, M. J. Ratain, G. M. Cragg, J. E. Wong, N. Saijo, D. R. Parkinson, Y. Fujiwara, R. Pazdur, D. J. Newman, R. Dagher, L. Di Leone. Anticancer drug discovery and develement throughout the world. J. Clin. Oncol.,2002,20:47-59.
[21]K. Tae, H. S. Lee, B. J. Park, C. W. Park, K. R. Kim, H. Y. Cho, L. H. Kim, B. L. Park, H. D. Shin. Association of DNA repair gene XRCCI polymorphisms with head and neck cancer in Korean population. Int. J. Cancer,2004,111(5):805-808.
[22]B. Hao, H. Wang, K. Zhou, Y. Li, X. Chen, G. Zhou, Y. Zhu, X. Miao, W. Tan, Q. Wei, D. Lin, F. He. Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma. Cancer Res., 2004,64(12):4378-4384.
[23]W. Zhou, G. Liu, D. P. Miller, S. W. Thurston, L. L. Xu, J. C. Wain, T. J. Lynch, L. Su, D. C. Christiani. Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk. Cancer Epidemiol Biomarkers Prev.,2003,12(4): 359-365.
[24]W. Zhou, G. Liu, D. P. Miller, S. W. Thurston, L. L. Xu, J. C. Wain, T. J. Lynch, L. Su, and D. C. Christiani. Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer. Cancer Res.,2002,62(5): 1377-1381.
[25]S. G. Leng, J. Cheng, Z. F. Pan, C. F. Huang, Y. Niu, Y. F. Dai, B. Li, F. S. He, Y. X. Zheng. Associations between XRCC1 and ERCC2 polymorphisms and DNA damage in peripheral blood lymphocyte among coke oven workers. Biomarkers,2004,9(4-5): 395-406.
[26]J. H. Hocijmakers. Genome maintenance mechanisms for P reventing cancer. Nature, 2001,411(6835):366-374.
[27]M. Goldfield. Some epidemiologic studies of transfusion-associated hepatitis. Infusionstherapie,1974,1(8):645-649.
[28]Q. L. Choo, G. Kuo, A. J. Weiner, L. R. Overby, D. W. Bradley, M. Houghton. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science,1989,244(4902):359-362.
[29]T. Arima, H. Shimomura, T. Nakajima, K. Kanai, H. Nagashima, T. Tsuji. Cloning of hepatitis C virus genomes and their properties. Gastroenterol. Jpn.,1990,25:72-76.
[30]A. Takamizawa, C. Mori, I. Fuke, S. Manabe, S. Murakami, J. Fujita, E. Onishi, T. Andoh, I. Yoshida, H. Okayama. Structure and organization of the hepatitis C virus genome isolated from human carriers. J. Virol.,1991,65(3):1105-1113.
[31]戚中田,杜平.丙型肝炎病毒与丙型肝焱.第1版.上海：上海科学技术出版社,1992.51-64.
[32]G. Randall, C. M. Rice, hepatitis C virus cell culture replication systems:their potential use for the development of antiviral therapies. Curr. Infect. Dis.,2001,14(6): 743-747.
[33]N. Kato. Genome of human hepatitis C virus (HCV):gene organization, sequence diversity, and variation. Microb. Comp. Genomics,2000,5(3):129-151.
[34]R. De Francesco, P. Neddermann, L. Tomei, C. Steinkuhler, P. Gallinari, A. Folgori. Biochemical and immunologic properties of the nonstructural proteins of the hepatitis C virus:implications for development of antiviral agents and vaccines. Semin. Liver Dis.,2000,20(1):69-83.
[35]A. Vario, R. Pistis, S. Boccato, A. Ferrari, A. Alberti. Prevalence and significance of hepatic steatosis in hepatitis C. J. Hepatol.,2003,38(2):179-180.
[36]G. K. K. Lau, H. Zhuang. Top hepatology issue in China. J. Gastroent. Hepatol.,2003, 18:A9.
[37]P. Skladal, C. S. Riccardi, H. Yamanaka, P. I. da Costa. Piezoelectric biosensors for real-time monitoring of hybridization and detection of the hepatitis C virus. J. Virol. Methods,2004,117:145-151.
[38]Q. L. Choo, A. J. Weiner, L. R. Overby, G. Kuo, M. Houghton, D. W. Bradley. Hepatitis C virus:the major causative agent of viral non-A, non-B hepatitis. Br. Med. Bull.,1990,46(2):423-441.
[39]S. L. Flamm. Chronic hepatitis C virus infection. JAMA,2003,289:2413-2417.
[40]R. Shirachi, H. Shiraishi, A. Tateda, K. Kikuchi, N. Ishida. Hepatitis "C" antigen in non-A, non-B post-transfusion hepatitis. Lancet,1978,2:853-856.
[41]A. Tateda, K. Kikuchi, Y. Numazaki, R. Shirachi, N. Ishida. Non-B hepatitis in Japanese recipients of blood transfusions:clinical and serologic studies after the introduction of laboratory screening of donor blood for hepatitis B surface antigen. J. Infect. Dis.,1979,139:511-518.
[42]G. Kuo, Q. L. Choo, H. J. Alter, G. L. Gitnick, A. G. Redeker, R. H. Purcell, T. Miyamura, J. L. Dienstag, M. J. Alter, C. E. Stevens. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science,1989, 244:362-364.
[43]G. J. Kotwal, B. M. Baroudy, I. K. Kuramoto, F. F. McDonald, G. M. Schiff, P. V. Holland, J. B. Zeldis. Detection of acute hepatitis C virus infection by ELISA using a synthetic peptide comprising a structural epitope. Proc. Natl. Acad. Sci. U.S.A.,1992, 89:4486-4489.
[44]杨东亮.丙型肝炎的病毒学检测指标及其临床意义.中华肝脏病杂志.2004,12(2)：104-105.
[45]王乐斌,赵久法.抗-HCV阴性献血员丙肝病毒感染及意义.临床医学.2000,25：442-442.
[46]Centers for Disease Control and Prevention (CDC). Hepatitis C virus transmission from an antibody-negative organ and tissue donor-United States.2000 to 2002. Morb. Mortal. Wkly. Rep.,2003,52:273-274.
[47]M. Willems, H. J. Metselaar, H. W. Tilanus, S. W. Schalm, R. A. de Man. Liver transplantation and hepatitis C. Transpl. Int.,2002,15:61-72.
[48]J. M. Pawlotsky. Use and interpretation of virological tests for hepatitis C. J. Hepatol., 2002,36:S65-S73.
[49]庄辉.重视丙型肝炎的研究.中华肝脏病杂志.2004,12：65-66.
[59]邢文革,郑怀竞.必须提高丙型肝炎病毒实验室检验结果的可信度.中华肝脏病杂志.2004,12：170-171.
[51]王宇明.重视我国丙型肝炎的研究.中华肝脏病杂志.2004,12：106-107.
[52]M. Darius, W. Takaji, K. Tokushige, R. I. Carlson, K. Krawczynski, J. R. Wands. Characterization of three novel monoclonal antibodies against hepatitis C virus core protein. J. Med. Virol.,1996,48:234-241.
[53]郭满盈,李谋深,李保仝,杨毓华.献血者血清中HCV NS3和核心蛋白抗原的检测及临床意义.中国输血杂志,2001,14：78-79.
[54]F. Lunel, P. Veillon, I. Fouchard-Hubert, V. Loustaud-Ratti, A. Abergel, C. Silvain, H. Rifflet, A. Blanchi, X. Causse, Y. Bacq, C. Payan. Fontevraud Study Group. Antiviral effect of ribavirin in early non-responders to interferon monotherapy assessed by kinetics of hepatitis C virus RNA and hepatitis C virus core antigen. J. Hepatol.,2003, 39(5):826-833.
[55]M. Maynard, M. Buti, J. I. Esteban, H. Tillmann, J. Wiegand, M. Manns, M. Martinot, P. Marcellin, P. Berthillon, G R. Picchio, P. Pradat, C. Trepo. Evaluation of the virological response during PEG-IFN/RIB treatment by HCV NAT or total HCV core AG testing leads to similar clinical decisions. J. Hepatol.,2003,38(2):156-156.
[56]G. Ballardini, P. Groff, F. Giostra, R. Francesconi, R. Miniero, S. Ghetti, D. Zauli, F. B. Bianchi. Hepatocellular codistribution of c100, c33, c22, and NS5 hepatitis C virus antigens detected by using immunopurified polyclonal spontaneous human antibodies. J. Hepatol.,1995,21:730-734.
[57]C. Pasquier, L. Bujan, M. Daudin, L. Righi, L. Berges, L. Thauvin, A. Berrebi, P. Massip, J. Puel, J. Izopet. Intermittent detection of hepatitis C virus (HCV) in semen from men with human immunodeficiency virus type 1 (HIV-1) and HCV. J. Med. Virol., 2003,69:344-349.
[58]陈佩兰,李琳,田惠英,陈良标.丙型肝炎患者外周血单个核细胞HCV和Fas抗原检测.军医进修学院学报,2000,21：215-217.
[59]T. Kashiwakuma, A. Hasegawa, T. Kajita, A. Takata, H. Mori, Y. Ohta, E. Tanaka, K. Kiyosawa, T. Tanaka, S. Tanaka, N. Hattori, M. Kohara. Detection of hepatitis C virus specific core protein in serum of patients by a sensitive fluorescence enzyme immunoassay (FEIA). J. Immunol. Methods,1996,190:79-89.
[60]K. Aoyagi, C. Ohue, K. Iida, T. Kimura, E. Tanaka, K. Kiyosawa, S. Yagi. Development of a simple and highly sensitive enzyme immunoassay for hepatitis C virus core antigen. J. Clin. Microbiol.,1999,37:1802-1808.
[61]李保仝,杨毓华,马勇,邵海枫,熊华,赵权,张小卫,武建国.丙型肝炎病毒核心抗原C33的测定.中华实验和临床病毒学杂志,1999,13：68-70.
[62]J. B. Kurtz, E. Boxall, N. Qusir, J. Shirley, D. Coleman, C. Chandler. The diagnostic singnificance of an assay for 'total' hepatitis C core antigen. J. Virol. Methods,2001,96: 127-132.
[63]A. M. Courouce, N. Le Marrec, F. Bouchardeau, A. Razer, M. Maniez, S. Laperche, N. Simon. Efficacy of HCV core antigen detection during the preseroconversion period. Transfusion,2000,40:1198-1202.
[64]S. R. Lee, J. Peterson, P. Niven, C. Bahl, E. Page, R. Deleys, D. Giordano-Schmidt, D. Baggett, G. Green. Efficacy of a hepatitis C virus core antigen enzyme-linked immunosorbent assay for the identification of 'window-phase' blood donations. Vox. Sanguinis,2001,80:19-23.
[65]S. B. Baylin, J. G. Herman. DNA hypermethylation in tumorigenesis:epigetics joins genetics. Trends Genet.,2000,16(4):168-174.
[66]A. Bird. DNA methylation patterns and epigenetic memory. Genes Dev.,2002,16 (1): 6-21.
[67]C. T. Wu, J. R. Morris. Genes, genetics, and epigenetics:A correspondence. Science, 2001,293(5532):1103-1105.
[68]A. P. Bird. CpG-rich islands and the function of DNA methylation. Nature,1986,. 321(6067):209-213.
[69]P. A. Jones, D. Takai. The role of DNA methylation in mammalian epigenetics. Science,2001,293(5532):1068-1070.
[70]Y. Yamada, H. Watanabe, F. Miura, H. Soejima, M. Uchiyama, T. Iwasaka, T. Mukai, Y. Sakaki, T. Ito. A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 21q. Genome Res.,2004,14(2):247-266.
[71]M. S. Greenblatt, W. P. Bennett, M. Hollstein, C. C. Harris. Mutations in the p53 tumor suppressor gene:Clues to cancer etiology and molecular pathogenesis. Cancer Res.,1994,54(18):4855-4878.
[72]S. Kimmins, P. Sassone-Corsi. Chromatin remoding and epigenetic features of germ cells. Nature,2005,434(7033):583-589.
[73]L. S. Dario, M. A. Rosa, E. Mariela, G. Roberto, C. Caterina. Chromatin remodeling agents for cancer therapy. Rev. Recent Clin. Trials,2008,3(3):192-203.
[74]G. Egger, G. N. Liang, A. Aparicio, P. A. Jones. Telomerase activity of sarcoma cell lines and fibroblasts is independent of P53 status. Nature,2004,429(6990):457-463.
[75]A. L. Carvalho, C. Jerenimo, M. M. Kim, R. Henrique, Z. Zhang, M. O. Hoque, S. Chang, M. Brait, C. S. Nayak, W. W. Jiang, Q. Claybourne, Y. Tokumaru, J. Lee, D. Goldenberg, E. Garrett-Mayer, S. Goodman, C. Moon, W. Koch, W. H. Westra, D. Sidransky, J. A. Califano. Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma. Clin. Cancer Res.,2008,14(1):97-107.
[76]A. S. Wilson, B. E. Power, P. L. Molloy. DNA hypomethylation and human diseases. Biochim. Biophys. Acta,2007,1775(1):138-162.
[77]M. Frommer, L. E. McDonald, D. S. Millar, C. M. Collis, F. Watt, G. W. Grigg, P. L. Molloy, C. L. Paul. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc. Natl. Acad. Sci. U.S.A., 1992,89(5):1827-1831.
[78]X. Liu, A. Clements, K. H. Zhao, R. Marmorstein. Structure of the human papillomavirus E7 oncoprotein and its mechanism for inactivation of the retinoblastoma tumor suppressor. J. Biol. Chem.,2006,281(1):578-586.
[79]A. M. Maxam, W. Gilbert. A new method for sequencing DNA. Proc. Natl. Acad. Sci. U.S.A.,1977,74(2):560-564.
[80]J. G. Herman, J. R. Graff, S. Myohanen, B. D. Nelkin, S. B. Baylin. Methylation-specific PCR:a novel PCR assay for methylation status of CpG islands. Proc. Natl. Acad. Sci. U.S.A.,1996,93(18):9821-9826.
[81]K. C. Kuo, R. A. McCune, C. W. Gehrke, R. Midgett, M. Ehrlich. Quantitative reversed-phase high performance liquid chromatographic determination of major and modified deoxyribonucleosides in DNA. Nucl. Acids Res.,1980,8(20):4763-4776.
[82]D. Deng, G. Deng, Y. Lv, J. Zhou, H. Xin. Analysis of the methylation in CpG island by denaturing high-performance liquid chromatography. National Medical Journal of China,2001,80(3):158-161.
[83]P. J. Oefner, G. K. Bonn, C. G. Huber, S. Nathakarnkitkool. Comparative study of capillary zone electrphoresis and high-performance liquid chromatography in the analysis of oligonucleotides and DNA. J. Chromatogr. A,1992,625(2):331-340.
[84]M. F. Fraga, E. Uriol, L. Borja-Diego, M. Berdasco, M. Esteller, M. J. Canal, R. Rodriguez. High-performance capillary electrophoretic method for the quantification of 5-methyl 2-deoxycytidine in genomic DNA:application to plant, animal and human cancer tissues. Electrophoresis,2002,23(11):1677-1681.
[85]张敏,汪国生,陈伟,汪云敏,李向培,阚明,何晓东.系统性红斑狼疮患者基因组DNA甲基化水平的研究.实用医学杂志,2009,25(6)：889-891.
[86]Y. M. Dennis Lo, I. H. N. Wong, J. Zhang, M. S. C. Tein, M. H. L. Ng, N. M. Hjelm. Quantitative analysis of aberrant p16 methylation using real-time quantitative methylation-specific polymerase chain reaction. Cancer Res.,1999,59(16): 3899-3903.
[87]C. A. Eads, K. D. Danenberg, K. Kawakami, L. B. Saltz, C. Blake, D. Shibata, P. V. Danenberg, P. W. Laird. MethyLight:a high-throughput assay to measure DNA methylation. Nucl. Acids Res.,2000,28(8):e32
[88]X. Yang, G. Qiu, S. Ye, X. Ding, Z. Ou, W. Wang, Y. He. Quantitative detection of DNA methylation by fluorescent quantitative real time PCR using SYBR Green I. Chinese J. Lab. Medicine,2007,30(4):433-434.
[89]C. Dabl, P. Guldberg. DNA methylation analysis techniques. Biogerontology,2003, 4(4):233-250.
[90]J. Worm, A. Aggerholm, P. Guldberg. In-tube DNA methylation profiling by fluorescence melting curve analysis. Clin. Chem.,2001,47(7):1183-1189.
[91]G. Clement, J. Benhattar. A methylation sensitive dot blot assay (MS-DBA) for the quantitative analysis of DNA methylation in clinical samples. J. Clin. Pathol.,2005, 58(2):155-158.
[92]F. Feng, H. Z. Wang, L. L. Han, S. Wang. Fluorescent conjugated polyelectrolyte as an indicator for convenient detection of DNA methylation. J. Am. Chem. Soc.,2008, 130(34):11338-11343.
[93]X. R. Duan, L. B. Liu, F. D. Feng, S. Wang. Cationic conjugated polymers for optical detection of DNA methylation, lesions, and single nucleotide polymorphisms. Acc. Chem. Res.,2010,43(2):260-270.
[94]K. Tanaka, K. Tainaka, T. Kamei, A. Okamoto. Direct labeling of 5-methylcytosine and its applications. J. Am. Chem. Soc.,2007,129(17):5612-5620.
[95]D. Kato, N. Sekioka, A. Ueda, R. Kurita, S. Hirono, K. Suzuki, O. Niwa. A nanocarbon film electrode as a platform for exploring DNA methylation. J. Am. Chem. Soc,2008,130(12):3716-3717.
[96]P. Wang, Z. B. Mai, Z. Dai, X. Y. Zou. Investigaton of DNA methylation by direct electrocatalytic oxidation. Chem. Commun.,2010,46(41):7781-7783.
[97]P. Hou, M. J. Ji, C. W. Ge, J. Y. Shen, S. Li, N. Y. He, Z. H. Lu. Detection of methylation of human p16Ink4a gene 5'-CpG islands by electrochemical method coupled with linker-PCR. Nucl. Acids Res.,2003,31(16):e92
[98]S. N. Liu, P. Wu, W. Li, H. Zhang, C. X. Cai. Electrochemical approach for detection of DNA methylation and assay of the methyltrans ferase activity. Chem. Commun., 2011,47,2844-2846.
[99]C. Chen, G. T. Song, J. S. Ren, X, G, Qu. A simple and sensitive colorimetric pH meter based on DNA conformational switch and gold nanoparticle aggregation. Chem. Commun.,2008, (46):6149-6151.
[100]J. Geng, K. G. Qu, J. S. Ren, X. G. Qu. Rapid and efficient screening of Alzheimer's desease β-amyloid inhibitors using label-free gold nanoparticles. Mol. BioSyst.,2010, 6(12):2389-2391.
[101]C. Chen, G. T. Song, X. J. Yang, J. S. Ren, X. G. Qu. The Kudo 5 total elbow replacement in the treatment of the rheumatoid elbow:results at a minimum of ten years. Biochimie,2010,92(10):1416-1421.
[102]X. L. Zhua, Y. X. Liu, J. H. Yang, Z. Q. Liang, G. X. Li. Gold nanoparticle-based colorimetric assay of single-nucleotide polymorphism of triplex DNA. Biosens. Bioelectron.,2010,25(9):2135-2139.
[103]W. Li, Z. L. Liu, H. Lin, Z. Nie, J. H. Chen, X. H. Xu, S. Z. Yao. Label-free colorimetric assay for methyltransferase activity based on a novel methylation-responsive DNAzyme strategy.Anal. Chem.,2010,82(5):1935-1941.
[104]X. Y. Xu, M. S. Han, C. A. Mirkin. A gold-nanoparticle-based real-time colorimetric screening method for endonuclease activity and inhibition. Angew. Chem. Int. Ed., 2007,46(19):3468-3470.
[105]W. Xu, X. J. Xue, T. H. Li, H. Q. Zeng, X. G. Liu. Ultrasensitive and selective colorimetric DNA detection by nicking endonuclease assisted nanoparticle amplification. Angew. Chem. Int. Ed.,2009,48(37):6849-6852.
[106]T. Liu, J. Zhao, D. M. Zhang, G. X. Li. Novel method to detect DNA methylation using gold nanoparticles coupled with enzyme-linkage reactions. Anal. Chem.,2010, 82(1):229-233.
[107]M. L. Gonzalgo, P. A. Jones. Rapid quantitation of methylation differences at specific sites using methylation-sensitive single nucleotide primer extension (Ms-SNuPE). Nucl. Acids Res.,1997,25(12):2529-2531.
[108]A. Bergerat, W. Guschlbauer, G. V. Fazakerley. Allosteric and catalytic binding of S-adenosylmethionine to escherichia coli DNA adenine methyltransferase monitored by 3H NMR. Proc. Natl. Acad. Sci. U.S.A.,1991,88(15):6394-6397.
[109]M. Maekawa, K. Sugano, H. Kashiwabara, M. Ushiama, S. Fujita, M. Yoshimori, T. Kakizoe. DNA methylation analysis using bisulfite treatment and PCR-single strand conformation polymorphism in colorectal cancer showing microsatellite instability. Biochem. Biophys. Res. Commun.,1999,262(3):671-676.
[110]A. Aggerholm, P. Guldberg, M. Hokland, P. Hokland. Extensive intra-and interindividual heterogeneity of p15INK4B methylation in acute myeloid leukemia. Cancer Res.,1999,59(2):436-441.
[111]C. M. Rodriguez Lopez, B. G. Asenjo, A. J. Lioyd, M. J. Wilkinson. Direct detection and quantification of methylation in nucleic acid sequences using high-resolution melting analysis. Anal. Chem.,2010,82(21):9100-9108.
[112]X. L. Wang, Y. L. Song, M. Y. Song, Z. X. Wang, T. Li, H. L. Wang. Fluorescence polarization combined capillary electrophoresis immunoassay for the sensitive detection of genomic DNA methylation. Anal. Chem.,2009,81(19):7885-7891.
[113]W. Nomura, C. F. Barbas. In vivo site-specific DNA methylation with a designed sequence-enabled DNA methylase. J. Am. Chem. Soc.,2007,129(28):8676-8677.
[114]M. Ehrich, J. Turner, P. Gibbs, L. Lipton, M. Giovanneti, C. Cantor, D. van den Boom. Cytosine methylation profiling of cancer cell lines. Proc. Nat. Acad. Sci. U.S.A., 2008,105(12):4844-4849.
[115]J. C. Mathers. Reversal of DNA hypomethylation by folic acid supplements:possible role in colorectal cancer prevention. Gut,2005,54(4):579-581.
[116]J. M. Trasler. Genete inpriting setting dpigenet patterns for the next generation. Reproduction Fertility and Development,2006,18(1-2):63-69.
[117]M. Esteller, P. G. Corn, S. B. Baylin, J. G. Herman. A gene hypermethylation profile of human cancer. Cancer Res.,2001,61(8):3225-3229.
[118]张静,来茂德,陈俭.结直肠癌及结直肠粘膜P16基因5’CpG岛甲基化状态的研究,中华病理学杂志,2000,29(2)：95-98.
[119]R. Henrique, F. R. Ribeiro, D. Fonseca, M. O. Hoque, A. L. Carvalho, V. L. Costa, M. Pinto, J. Oliveira, M. R. Teixeira, D. Sidransky, C. Jeronimo. High promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients. Clin. Cancer Res.,2007,13(20):6122-6129.
[120]M. R. Abbaszadegan, O. Moaven, H. R. Sima, K. Ghafarzadegan, A. A'rabi, M. N. Forghani, H. R. Raziee, A. Mashhadinejad, M. Jafarzadeh, E. Esmaili-Shandiz, E. Dadkhah..P16 promoter hypermethylation:a useful serum marker for early detection of gastric cancer. World J. Gastroenterol.,2008,14(13):2055-2060.
[121]C. B. Wilcox, B. E. Baysal, H. H. Gallion, M. A. Strange, J. A. DeLoia. High resolution methylation analysis of the BRCA1 promoter in ovarian tumors. Cancer Genet. Cytogenet.,2005,159(2):114-122.
[122]Y. L. Choi, S. Y. Kang, Y. K. Shin, J. S. Choi, S. H. Kim, S. J. Lee, D. S. Bae, G. Ahn. Aberrant hypermethylation of RASSF1A promoter in ovarian borderline tumors and carcinomas. Virchows Arch.,2006,448(3):331-336.
[123]M. Widschwendter, G. C. Jiang, C. Woods, H. M. Muller, H. Fiegl, G. Goebel, C. Marth, E. Muller-Holzner, A. G. Zeimet, P. W. Laird, M. Ehrlich. DNA hypomethylation and ovarian cancer biology. Cancer Res.,2004,64(13):4472-4480.
[124]O. El-Maarri, U. Herbiniaux, J. Walter, J. Oldenburg. A rapid, quantitative, non-radioactive bisulfite-SNuPE-IP RP HPLC assay for methylation analysis at specific CpG sites. Nucl. Acids Res.,2002,30(6):e25.
[125]K. Rand, W. J. Qu, T. Ho, S. J. Clark, P. Molloy. Conversion-specific detection of DNA methylation using real-time polymerase chain reaction (ConLight-MSP) to avoid false positives. Methods,2002,27(2):114-120.
[126]M. W. Y. Chan, L. W. Chan, N. L. S. Tang, K. W. Lo, J. H. M. Tong, A. W. H. Chan, H. Y. Cheung, W. S. Wong, P. S. F. Chan, F. M. M. Lai, K. F. To. Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients. Int. J. cancer,2003,104(5):611-616.
[127]J. Huang, X. Zhang, M. Zhang, J. D. Zhu, Y. L. Zhang, Y. Lin, K. S. Wang, X. F. Qi, Q. Zhang, G. Z. Liu, J. Yu, Y. Cui, P. Y. Yang, Z. Q. Wang, Z. G. Han. Up-regulation of DLK1 gene could contribute to human hepatocellular carcinoma. Carcinogenesis,2007, 28(5):1094-1103.
[128]J. D. Zhu. The altered DNA methylation pattern and its implications in liver cancer. Cell Res.,2005,15(4):272-280.
[129]J. Zhu. DNA methylation and tumors diagnosis. Journal of Diagnostics Concepts & Practice,2009,8(1):15-19.
[130]J. D. Zhu. Life expectancy benefits of gastric bypass surgery. J. Hepatobiliary Pancreat. Surg.,2006,13(4):265-273.
[131]J. D. Zhu, X. B. Yao. Use of DNA methylation for cancer detection and molecular classification. J. Biochem. Mol. Biol.,2007,40(2):135-141.
[132]M. F. Paz, M. F. Fraga, S. Avila, M. Z. Guo, M. Pollan, J. G. Herman, M. Esteller. A systematic profile of DNA methylation in human cancer cell lines. Cancer Res.,2003, 63(5):1114-1121.
[133]B. S. Mann, J. R. Johnson, M. H. Cohen, R. Justice, R. Pazdur. FDA approval summary:vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist,2007,12(10):1247-1252.
[134]J. A. Karam, J. H. Fan, J. Stanfield, E. Richer, E. A. Benaim, E. Frenkel, P. Antich, A. I. Sagalowsky, R. P. Mason, J. T. Hsieh. The use of histone deacetylase inhibitor FK228 and DNA hypomethylation agent 5-azacytidine in human bladder cancer therapy. Int. J. Cancer,2007,120(8):1795-1802.
[135]H. Kasai, K. Kawai. DNA methylation at the C-5 position of cytosine by methyl radicals:A possible role for epigenetic change during carcinogenesis by environmental agents. Chem. Res. Toxicol.,2009,22(6):984-989.
[136]P. Siedlecki, R. G. Boy, T. Musch, B. Brueckner, S. Suhai, F. Lyko, P. Zielenkiewicz. Discovery of two novel, small-molecule inhibitors of DNA methylation. J. Med. Chem.,2006,49(2):678-683.
[137]K. Miki, E. Shimizu, S. Yano, K. Tani, S. Sone. Demethylation by 5-aza-2'-deoxycytidine (5-azadC) of p16INK4A gene results in downregulation of vascular endothelial growth factor expression in human lung cancer cell lines. Oncol. Res.,2000,12(8):335-342.
[138]X. Cui, T. Wakai, Y. Shirai, N. Yokoyama, K. Hatakeyama, S. Hirano. Arsenic trioxide inhibits DNA methyltransferase and restores methylation-silenced genes in human liver cancer cells. Hum. Pathol.,2006,37(3):298-311.
[139]K. O. Uhm, E. S. Lee, Y. M. Lee, H. S. Kim, Y. N. Park, S. H. Park. Aberrant promoter CpG islands methylation of tumor suppressor genes in cholangiocarcinoma. Oncol. Res.,2008,17(4):151-157.
[140]N. Fujita, S. Horiike, R. Sugimoto, H. Tanaka, M. Iwasa, Y. Kobayashi, K. Hasegawa, N. Ma, S. Kawanishi, Y. Adachi. Hepatic oxidative DNA damage correlates with iron overload in chronic hepatitis C patients. Free Radical Biol. Med.,2007,42(3): 353-362.
[141]K. Kiyosawa, T. Sodeyama, E. Tanaka, Y. Gibo, K. Yoshizawa, Y. Nakano, S. Furuta, Y. Akahane, K. Nishioka, R. H. Purcell, H. J. Alter. Interrelationship of blood transfusion, nonA, nonB hepatitis and hepatocellula r carcionoma; Analysis by detection of antibody to hepatitis C virus. J. Hepatol.,1990,12:671-675.
[142]H. Le Guillou-Guillemette, F. Lunel-Fabiani. Detection and quantification of serum or plasma HCV RNA:mini review of commercially available assays, in hepatitis C: Methods and Protocols (2nd edn); H. Tang, Ed., Humana Press:Totowa, NJ,2009, Vol. 510, pp.3-14.
[143]W. P. Hofmann, V. Dries, E. Herrmann, B. Gartner, S. Zeuzem, C. Sarrazin. Comparison of transcription mediated amplification (TMA) and reverse transcription polymerase chain reaction (RT-PCR) for detection of hepatitis C virus RNA in liver tissue. J. Clin. Virol.,2005,32:289-293.
[144]E. Engvall, P. Perlmann. Enzyme-linked immunosorbent assay, elisa:Ⅲ. quantitation of specific antibodies by enzyme-labeled anti-immunoglobulin in antigen-coated tubes. J. Immunol.,1972,109:129-135
[145]C. L. van der Poel, H. W. Reesink, J. J. P. van Boven, H. T. M. Cuypers, I. Winkel, P. J. Exel-Oehlers, W. Schaasberg, P. N. Lelie, A. J. Weiner, A. Polito, S. Quan, R. Di Nello, M. Houghton, D. Mulder-Folkerts, A. Leentvaar-Kuypers. Confirmation of hepatitis C virus infection by new four-antigen recombinant immunoblot assay. The lancet,1991,337(8737):317-319.
[146]M. W. Pfaffl. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res.,2001,29(9):e45.
[147]M. Musiani, S. Venturoli, G. Gallinella, M. Zerbini. Qualitative PCR-ELISA protocol for the detection and typing of viral genomes. Nature Protocols,2007,2, 2502-2510.
[148]M. L. Collins, B. Irvine, D. Tyner, E. Fine, C. Zayati, C. Chang, T. Horn, D. Ahle, J. Detmer, L. P. Shen, J. Kolberg, S. Bushnell, M. S. Urdea, D. D. Ho. A branched DNA signal amplification assay for quantification of nucleic acid targets below 100 molecules/ml. Nucleic Acids Research,1997,25(15):2979-2984.
[149]R. S. Lanciotti, A. J. Kerst. Nucleic Acid Sequence-Based Amplification Assays for Rapid Detection of West Nile and St. Louis Encephalitis Viruses. J. Clin. Microbiol., 2001,39(12):4506-4513.
[150]T. Umemura, R. Y. H. Wang, C. Schechterly, J. W. Shih, K. Kiyosawa, H. J. Alter. Quantitative analysis of anti-hepatitis C virus antibody-secreting B cells in patients with chronic hepatitis C. J. Hepatol.,2006,43(1):91-99.
[151]S. Erensoy. Diagnosis of hepatitis C virus (HCV) infection and laboratory monitoring of its therapy. J. Clin. Virol.,2001,21:271-281.
[152]S. C. Lee, A. Antony, N. Lee, J. Leibow, J. Q. Yang, S. Soviero, K. Gutekunst, M. Rosenstraus. Improved version 2.0 qualitative and quantitative AMPLICOR reverse transcription-PCR tests for hepatitis C virus RNA:calibration to international units, enhanced genotype reactivity, and performance characteristics. J. Clin. Microbiol., 2000,38(11):4171-4179.
[153]Y. C. Lin, M. Y. Huang, K. C. Young, T. T. Chang, C. Y. Wu. A rapid micro-polymerase chain reaction system for hepatitis C virus amplicication. Sens. Actuators B,2000,71:2-8.
[154]R. C. Hollingsworth, P. Sillekens, P. Van Deursen, K. R. Neal, W. L. Lrving, Trent HCV Study Group. Serum HCV RNA levels assessed by quantitative NASBA:stability of viral load over time, and lack of correlation with liver disease. J. Hepatol.,1996, 25(3):301-306.
[155]M. Damen, P. Sillekens, H. T. M. Cuypers, I. Frantzen, R. Melsert. Characterization of the quantitative HCV NASBA assay. J. Virol. Methods,1999,82(1):45-54.
[156]A. Guichon, H. Chiaprelli, A. Martinez, C. Rodrigues, A. Trento, C. J. Russi, G. Carballal. Evaluation of a new NASBA assay for the qualitative detection of hepatitis C virus based on the NucliSens Basic Kit reagents. J. Clin. Virol.,2004,29(2):84-91.
[157]P. M. Richalet-Secordel, F. Poisson, M. H. V. van Regenmortel. Uses of biosensor technology in the development of probes for viral diagnosis. Clin. Diagn. Virol.,1996, 5:111-119.
[158]D. OiMeara, Z. B. Yun, A. Sonnerborg, O. Weiland, J. Lundeberg. Cooperative oligonucleotides mediating direct capture of hepatitis C virus RNA from serum. J. Clin. Microbiol.,1998,36(9):2454-2459.
[159]J. Griffin, A. K. Singh, D. Senapati, E. Lee, K. Gaylor, J. Jones-Boone, P. C. Ray. Sequence specific HCV-RNA quantification using size dependent nonlinear optical properties of gold nanoparticles. Small,2009,5(7):839-845.
[160]G. Bildan, M. Billon, T. Livache, G. Mathis, A. Roget, L. M. Torres- Rodriguez. Conducting polymers as a link between biomolecules and microelectronics. Synth. Met., 1999,102:1363-1365.
[161]C. S. Riccardi, K. Dahmouche, C. V. Santilli, P. I. da Costa, H. Yamanaka. Immobilization of streptavidin in sol-gel films:application on the diagnosis of hepatitis C virus. Talanta,2006,70(3):637-643.
[162]C. S. Riccardi, C. Kranz, J. Kowalik, H.Yamanaka, B. Mizaikoff, M. Josowicz. Label-free DNA detection of hepatitis C virus based on modified conducting polypyrrole films at microelectrodes and atomic force microscopy tip-integrated electrodes. Anal. Chem.,2008,80(1):237-245.
[163]A. E. Radi, J. L. A. Sanchez, E. Baldrich, C. K. O'Sullivan. Reagentless, reusable, ultrasensitive electrochemical molecular beacon aptasensor. J. Am. Chem. Soc.,2006, 128(1):117-124.
[164]Y. Zhang, Y. Wang, H. Wang, J. H. Jiang, G L. Shen, R. Q. Yu, J. H. Li. Based on the proximity-dependent surface hybridization assay. Anal. Chem.,2009,81(5): 1982-1987.
[165]Z. Fang, S. O. Kelley. Direct electrocatalytic mRNA detection using PNA-nanowire sensors. Anal. Chem.,2009,81(2):612-617.
[166]X. Zhang, K. Jiao, S. Liu, Y. W. Hu. Readily reusable electrochemical DNA hybridization biosensor based on the interaction of DNA with single-walled carbon nanotubes. Anal. Chem.,2009,81(15):6006-6012.
[167]J. S. Swensen, Y. Xiao, B. S. Ferguson, A. Lubin, R. Lai, A. J Heeger, K. W. Plaxco, H. T. Soh. Continuous, real-time monitoring of cocaine in undiluted blood serum via a microfluidic, electrochemical aptamer-based sensor. J. Am. Chem. Soc.,2009,131(12): 4262-4266.
[168]K. J. Cash, A. J. Heeger, K. W. Plaxco, Y. Xiao. Optimization of a reusable, DNA pseudoknot-based electrochemical sensor for sequence-specific DNA detection in blood serum. Anal. Chem.,2009,81(2):656-661.
[169]B. Li, Y. Du, H. Wei, S. Dong. Unmodified gold nanoparticles as a colorimetric probe for potassium DNA aptamers. Chem. Commun.,2007:3780-3782.
[170]J. Yuan, W. Guo, X. Yang, E. Wang. Anticancer drug-DNA interactions measured using a photoinduced electron-transfer mechanism based on luminescent quantum dots. Anal. Chem.,2009,81(1):362-368.
[171]H. X. Ju, Y. K. Ye, Y. L. Zhu. Electrochemical study of interaction between nile blue and immobilized single- or double-stranded DNA and its application for cDNA recognition. Electrochim. Acta,2005,50(6):1361-1367.
[172]C. Yao, T. Zhu, J. Tang, R. Wu, Q. Chen, M. Chen, B. Zhang, J. Huang, W. Fu,. Hybridization assay of hepatiis B virus by QCM peptide nucleic acid. Biosens. Bioelectron.,2008,23(6):879-885.
[173]H. T. Zhao, H. X. Ju. Biosensor for hepatitis B virus DNA PCR production and electrochemical study of the interaction of di (2,2'-bipyridine) osmium (Ⅲ) with DNA. Electroanalysis,2004,16(19):1642-1646.
[174]M. Kobayashi, K. B. Takashi, M. Saito, S. Kaji, M. Oomura. Electrochemical DNA quantification based on aggregation induced by Hoechst 33258. Electrochem. Commun.,2004,6(4):337-343.
[175]T. K. Ye, J. H. Zhao, F. Yan, Y. L. Zhu, H. X. Ju. Electrochemical behavior and detection of hepatitis B virus DNA PCR production at gold electrode, Biosens. Bioelectron.,2003,18(12):1501-1508.
[176]H. X. Ju, Y. K. Ye, J. H. Zhao, Y. L. Zhu. Hybridization biosensor using di (2, 2'-bipyridine) osmium (Ⅲ) as electrochemical indicator for detection of polymerase chain reaction product of hepatitis B virus DNA. Anal. Biochem.,2003,313:255-261.
[177]B. Meric, K. Kerman, D. Ozkan, A. Erdem, M. Ozsoz. Electrochemical DNA biosensor for the detection of TT and Hepatitis B virus from PCR amplified real samples by using Methylene Blue. Talanta,2002,56(5):837-846.
[178]D. K. Xu, K. Huang, Z. H. Liu, L. Ma. Microfabricated disposable DNA sensor based on enzymatic amplfication electrochemical detection. Electroanalysis,2001, 13(10):882-887.
[179]G. Nardone, J. George, J. G Chirikjian. Differences in the kinetic properties of BamHI endonuclease and methylase with linear DNA substrates. J. Biol. Chem.,1986, 261(26):12128-12133.
[180]S. Krishnan, E. G. Hvastkovs, B. Bajrami, I. Jansson, J. B. Schenkman, J. F. Rusling. Dehydroacetic acid and its derivatives in organic synthesis:synthesis of some new 2-substituted-4-(5-bromo-4-hydroxy-6-methyl-2H-pyran-2-one-3-y1) thiazoles. Chem. Commun.,2007:1713-1715.
[191]Y. Jin, W. Lu, J. Hu, X. Yao, J. H. Li. Site-specific DNA cleavage by EcoRI endounclease real-time probed by ferrocene capped gold nanoparticles. Electrochem. Commun.,2007,9(5):1086-1090.
[182]G Piperberg, O. I. Wilner, O. Yehezkeli, R. Tel-Vered, I. Willner. Control of bioelectrocatalytic transformations on DNA scaffolds. J. Am. Chem. Soc.,2009, 131(25):8724-8725.
[183]F. Ricci, A. J. Bonham, A. C. Mason, N. O. Reich, K. W. Plaxco. Reagentless, electrochemical approach for the specific detection of double- and single-stranded DNA binding proteins. Anal. Chem.,2009,81(4):1608-1614.
[184]M. Fojta, T. Kubicarova, E. Paleaek. Cleavage of supercoiled DNA by deoxyribonuclease I in solution and at the electrode surface. Electroanalysis,1999, 11(14):1005-1012.
[185]Z. Dai, J. Chen, F. Yan, H. Ju, Electrochemical sensor for immunoassay of carcinoembryonic antigen based on thionine monolayer modified gold electrode. Cancer Detection and Prevention,2005,29 (3):233-240.
[186]D. OiMeara, Z. B. Yun, A. Sonnerborg O. Weiland, J. Lundeberg. Cooperative oligonucleotides mediating direct capture of hepatitis C virus RNA from serum. J. Clin. Microbiol.,1998,36(9):2454-2459.
[187]J. Griffin, A. K. Singh, D. Senapati, E. Lee, K. Gaylor, J. Jones-Boone, P. C. Ray. Sequence specific HCV-RNA quantification using size dependent nonlinear optical properties of gold nanoparticles. Small,2009,5(7):839-845.
[188]H. A. Kozlowska, B. E. Conway, A. Hamelin, L. J. Stoicoviciu. Elementary steps of electrochemical oxidation of single-crystal planes of Au Part Ⅱ. A chemical and structural basis of oxidation of the (Ⅲ) plane. J. Electroanal. Chem.,1987,228(1): 429-453.
[189]R. Szamocki, A. Velichko, C. Holzapfel, A. Lasagni, F. Miicklich, S. Ravaine, A. Kuhn, R. Hempelmann. Macroporous ultramicroelectrodes for improved electroanalytical measurements. Anal. Chem.,2007,79(2):533-539.
[190]H. Qian, L. He. Surface-initiated activators generated by electron transfer for atom transfer radical polymerization in detection of DNA point mutation. Anal. Chem.,2009, 81(11):4536-4542.
[191]R. Lao, S. Song, H. Wu, L. Wang, Z. Zhang, L. He, C. Fan. Electrochemical interrogation of DNA monolayers on gold surfaces. Anal. Chem.,2005,77(19): 6475-6480.
[192]A. B. Steel, T. M. Herne, M. J. Tarlov. Electrochemical quantitation of DNA immobilized on gold. Anal. Chem.,1998,70(22):4670-4677.
[193]X. Luo, T. M. H. Lee, I. M. Hsing. Immobilization-free sequence-specific electrochemical detection of DNA using ferrocene-labeled peptide nucleic acid. Anal. Chem.,2008,80(19):7341-7346.
[194]B. Hinsch, M. R. Kula. Physical and kinetic properties of the site specific endonuclease BamHI from Bacillus amylolique-faciens. Nucleic Acids Res.,1980,8(3): 623-633.
[195]L. E. Englerl, P. Sapienzal, L. F. Dorner, R. Kucera, I. Schildkraut, L. Jen-Jacobson. The energetics of the interaction of BamHI endonuclease with its recognition site GGATCC. J. Mol. Bioi.,2001,307:619-636.
[196]A. J. Bard, L. R. Faulkner, Electrochemical Methods:Fundamentals and Applications (2nd edn), John Wiley & Sons:New York,2001.
[197]H. Zhao, H. Ju. Multilayer membranes for glucose biosensing via layer-by-layer assembly of multiwall carbon nanotubes and glucose oxidase, Anal. Biochem.,2006, 350:138-144.
[198]Y. Yin, P. Wu, Y. Lu, P. Du, Y. Shi, C. X. Cai. Immobilization and direct electrochemistry of cytochrome c at a single-walled carbon nanotube-modified electrode, J. Solid State Electrochem.,2007,11:390-397.
[199]M. Wang, Y. Shen, Y. Liu, T. Wang, F. Zhao, B. Liu, S. Dong. Direct electrochemistry of microperoxidase 11 using carbon nanotube modified electrodes J. Electroanal. Chem.,2005,578:121-127.
[200]F. Patolsky, Y. Weizmann, I. Willner. Redox-active nucleic-acid replica for the amplified bioelectrocatalytic detection of viral DNA. J. Am. Chem. Soc.,2002,124(5): 770-772.
[201]J. Wang, J. Li, A. J. Baca, J. Hu, F. Zhou, W. Yan, D. W. Pang. Amplified voltammetric detection of DNA hybridization via oxidation of ferrocene caps on gold nanoparticle/streptavidin conjugates. Anal. Chem.,2003,75(15):3941-3945.
[202]J. Liu, S. Tian, L. Tiefenauer, P. E. Nielson, W. Knoll. Simultaneously amplified electrochemical and surface plasmon resonce optical detection of DNA hybridization based on ferrocene-streptavidin conjugates. Anal. Chem.,2005,77(9):2756-2761.
[203]A. S. Georgopoulou, D. M. P. Mingos, A. J. P. White, D. J. Williams, B. R. Horrocks, A. Houlton. Bifunctional ferrocene derivatives for molecular recognition of DNA duplexes. J. Chem. Soc., Dalton Trans.,2000:2969-2974.
[204]A. Anne, A. Bouhardon, J. Moiroux.3'-ferrocene-labeled oligonucleotide chains end-tethered to gold electrode surfaces:Novel model systems for exploring flexibility of short DNA using cyclic voltammetry. J. Am. Chem. Soc.,2003,125(5):1112-1113.
[205]E. Laviron. The use of linear potential sweep voltammetry and of a.c. voltammetry for the study of the surface electrochemical reaction of strongly adsorbed systems and of redox modified electrodes. J. Electroanal. Chem.,1979,100(1-2):263-270.
[206]K. Uosaki, Y. Sato, H. Kita. Electrochemical characteristics of a gold electrode modified with a self-assembled monolayer of ferrocenylalkanethiols. Langmuir,1991, 7(7):1510-1514.
[207]C. Fan, K. W. Plaxco, A. J. Heeger. Electrochemical interrogation of conformational changes as a reagentless method for the sequence-specific detection of DNA. Proc. Natl. Acad. Sci. U.S.A.,2003,100(16):9134-9137.
[208]W. C. Liao, J. Ho. Attomole DNA electrochemical sensor for the detection of escherichia coli O157. Anal. Chem.,2009,81(7):2470-2476.
[209]M. A. Joyce, D. L. Tyrrell. The cell biology of hepatitis C virus. Microb. Infect., 2010,14:263-271.
[210]M. A. Joyce, K. A. Walters, S. E. Lamb, M. M. Yeh, L. F. Zhu, N. Kneteman, J. S. Doyle, M. G. Katze, D. L. Tyrrell. HCV induces oxidative and ER stress, and sensitizes infected cells to apoptosis in SCID/Alb-uPA mice. PloS Pathog.,2009,5(2):e1000291.
[211]J. R. Thomas, P. J. Hergenrother. Targeting RNA with small molecules. Chem. Rev., 2008,108(4):1171-1224.
[212]H. Huang, Y. Chen, J. Ye. Inhibition of hepatitis C virus replication by peroxidation of arachidonate and restoration by vitamin E. Proc. Natl. Acad. Sci. U.S.A.,2007, 104(47):18666-18670.
[213]S. N. Liu, Y. J. Hu, J. Jin, H. Zhang, C. X. Cai. Electrochemical detection of hepatitis C virus based on site-specific DNA cleavage of BamHI endonuclease. Chem. Commun.,2009,1635-1637.
[214]S. N. Liu, Q. Wang, D. X. Chen, J. Jin, Y. J. Hu, P. Wu, H. Zhang, C. X. Cai. Electrochemical approach for the specific detection of hepatitis C virus based on site-specific DNA cleavage of BamHI endonuclease. Anal. Methods,2009,2:135-142.
[215]N. A. Antonishyn, V. M. Ast, R. R. McDonald, R. K. Chaudhary, L. Lin, A. P. Andonov, G. B. Horsman. Rapid genotyping of hepatitis C virus by primer-specific extension analysis. J. Clin. Microbiol.,2005,43(10):5158-5163.
[216]M. D. William-Carey, W. Carey. Tests and screening strategies for the diagnosis of hepatitis C. Clin. J. Med.,2003,70:S7-S13.
[217]R. Zhang, S. C. Du, Y. Tian. Regional distribution of mutants with BamHI site of hepatitis C virus genotype 1b 5' noncoding region. China J. Modern Med.,2005,15: 3082-3084.
[218]K. C. Grabar, R. G. Freeman, M. B. Hommer, M. J. Natan. Preparation and characterization of Au colloid monolayers. Anal. Chem.,1995,67(4):735-743.
[219]L. Zhang, X. Jiang. Attachment of gold nanoparticles to glassy carbon electrode and its application for the voltammetric resolution of ascorbic acid and dopamine. J. Electroanal. Chem.,2005,583(2):292-299.
[220]A. Hamelin. Cyclic voltammetry at gold single-crystal surfaces. Part 1. Behaviour at low-index faces. J. Electroanal. Chem.,1996,407(1-2):1-11.
[221]H. Park, S. B. Lee, K. Kim, M. S. Kim. Surface-enhanced Raman scattering of p-aminobenzoic acid at Ag electrode. J. Phys. Chem.,1990,94(19):7576-7580.
[222]D. Zeisel, B. Dutoit, V. Deckert, T. Roth. Optical spectroscopy and laser desorption on a nanometer scale. Anal. Chem.,1997,69(4):749-754.
[223]M. J. Gong, T. Han, C. X. Cai, T. H. Lu, J. Y. Du. Fabrication and characterization of DNA-thionine-carbon nanotubes nanocomposites. J. Electroanal. Chem.,2008, 623(1):8-14.
[224]P. Qiu, X. Y. Cai, L. Wang, J. R. Greene, B. Malcolm. Colony shape as a genetic trait in the pattern-forming bacillus mycoides. BMC Microbiol.,2002,2:1471-2180.
[225]A. Grakoui, D. W. McCourt, C. Wychowski, S. M. Feinstone, C. M. Rice. Characterization of the hepatitis C virus-encoded serine proteinase:determination of proteinase-dependent polyprotein cleavage sites. J. Virol.,1993,67(5):2832-2843.
[226]B. Weinhold. Epigenetics:the science of change. Environ. Health Perspect.,2006, 114:A160-A167.
[227]J. S. Choy, S. Wei, J. Y. Lee, S. Tan, S. Chu, T. H. Lee. DNA methylation increases nucleosome compaction and rigidity. J. Am. Chem. Soc.,2010,132(6):1782-1783.
[228]E. Li, C. Beard, R. Jaenisch. Role for DNA methylation in genomic imprinting. Nature,1993,366(6453):362-365.
[229]E. Heard, P. Clerc, P. Avner. X-chromosome inactivation in mammals. Annu. Rev. Genet.,1997,31:571-610.
[230]W. Reik, F. Santos, W. Dean. Mammalian epigenomics:reprogramming the genome for development and therapy. Theriogenology,2003,59(1):21-32.
[231]C. P. Walsh, J. R. Chaillet, T. H. Bestor. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat. Genet.,1998,20:116-117.
[232]R. Z. Chen, U. Pettersson, C. Beard, L. Jackson-Grusby, R. Jaenisch. DNA hypomethylation leads to elevated mutation rates. Nature,1998,395(6697):89-93.
[233]A. P. Bird, A. P. Wolffe. Methylation-induced repression belts, braces, and chromatin. Cell,1999,99(5):451-454.
[234]J. Kim, A. Kollhoff, A. Bergmann. Methylation-sensitive binding of transcription factor YY1 to an insulator sequence within the paternally expressed imprinted gene, Peg3. Hum. Mol. Genet.,2003,12(3):233-245.
[235]K. D. Roberts. DNA methylation, methyltransferases and cancer. Oncogene,2001, 20(24):3139-3155.
[236]V. Colot, J. L. Rossignol. Eukaryotic DNA methylation as an evolutionary device. Bioessays,1999,21(5):402-411.
[237]S. B. tephen, J. G. Herman. DNA hypermethylation in tumorigenesis. Trends Genet., 2000,16(4):168-174.
[238]B. Brueckner, F. Lyko. DNA methyltransferase inhibitors:old and new drugs for an epigenetic cancer therapy. Trends Pharmacol. Sci.,2004,25:551-554.
[239]R. J. Klose, A. P. Bird. Genomic DNA methylation:the mark and its mediators. Trends Biochem. Sci.,2006,31:89-96.
[240]P. A. Jones, Baylin, S. B. The fundamental role of epigenetic events in cancer, Nat. Rev. Genet.,2002,3:415-428.
[241]M. Esteller. CpG island hypermethylation and tumor suppressor genes:a booming present, a brighter future. Oncogene,2002,21(35):5427-5440.
[242]J. R. Poeter, C. I. Stains, D. J. Segal, I. Ghosh. Split β-lactamase sensor for the sequence-specific detection of DNA methylation. Anal. Chem.,2007,79(17): 6702-6708.
[243]F. Lyko, B. H. Ramsahoye, R. Jaenisch. Development:DNA methylation in drosophila melanogaster. Nature,2000,408:538-540.
[244]G. P. Pfeifer, S. D. Steigerwald, P. R. Mueller, B. Wold, A. D. Riggs. Genomic sequencing and methylation analysis by ligation mediated PCR, Science,1989,246: 810-813.
[245]I. Hatada, Y. Hayashizaki, S. Hirotsune, H. Komatsubara, T. A. Mukai. A genomic scanning method for higher organisms using restriction sites as landmarks. Proc. Natl. Acad. Sci. U.S.A.,1991,88(21):9523-9527.
[246]X. Duan, L. Liu, F. Feng, S. Wang. Cationic conjugated polymers for optical detection of DNA methylation, Acc. Chem. Res.,2010,43:260-270.
[247]X. Wang, Y. Song, M. Song, Z Wang. Fluorescence polarization combined capillary electrophoresis immunoassay for the sensitive detection of genomic DNA methylation. Anal. Chem.,2009,81(19):7885-7891.
[248]J. Li, H. Yan, K. Wang, W. Tan, X. Zhou. Hairpin fluorescence DNA probe for real-time monitoring of DNA methylation. Anal. Chem.,2007,79(3):1050-1056.
[249]G. Song, C. Chen, J. Ren, X. Qu. A simple, universal colorimetric assay for endonuclease/methyltransferase activity and inhibition based on an enzyme-responsive nanoparticle system. ACS Nano.,2009,3(5):1183-1189.
[250]M. F. Fraga, R. Rodriguez, M. J. Canal. Rapid quantification of DNA methylation by high performance capillary electrophoresis. Electrophoresis,2000,21(14):2990-2994.
[251]S. Friso, S. W. Choi, G. G. Dolnikowski, J. Selhub. A method to assess genomic DNA methylation using high-performance liquid chromatography/electrospray ionization mass spectrometry. Anal. Chem.,2002,74(17):4526-4531.
[252]H. Angerstein-Kozlowska, B. E. Conway, A. Hamelin, L. Stoicoviciu. Elementary steps of electrochemical oxidation of single-crystal planes of Au part Ⅱ. A chemical and structural basis of oxidation of the (Ⅲ) plane. J. Electroanal. Chem.,1987,228: 429-453.
[253]Y. L. Zhang, Y. Wang, H. B. Wang, J. H. Jiang, G. L. Shen, R. Q. Yu, J. H. Li. Based on the proximity-dependent surface hybridization assay. Anal. Chem.,2009,81: 1982-1987.
[254]J. K. Christman.5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation:implications for cancer therapy. Oncogene,2002,21:5483-5495.