小鼠毒理基因芯片在化学促癌研究中的初步应用
|
摘要
化学致癌是多因素、多基因综合作用的多阶段过程,目前认为多阶段化学致癌可分为启动、促癌和进展三个阶段,其中促癌阶段具有特别的意义。由于促癌作用在早期是可逆的,因而及时识别并消除促癌因素对于肿瘤的预防具有重要价值,同时环境中大量的物理、化学和生物因子被发现能在肿瘤发生中起促癌作用,因此有必要建立快速有效的促癌物识别评价方法,但这正是传统毒理学研究的难题。此外,目前对促癌机制的研究相对滞后,由于促癌作用也是一个多基因协同作用的过程,可能存在多种信号通路构成的网络调控体系,因而单基因检测方法并不适合促癌作用机理的研究。
毒理基因组学的出现引导研究者从基因组角度进行毒理研究,基因芯片技术因为具有高通量平行处理的特点而成为毒理基因组研究的主要工具。基因芯片表达谱分析能实现对成千上万个基因表达的平行检测,易于发现化合物的特征性表达变化,因而在对包括致癌物在内的毒物检测识别和作用机理研究方面有了越来越广泛的应用,这提示此技术也能有效用于促癌物的检测识别和促癌作用机理的研究。因此,本课题在建立小鼠毒理基因芯片表达谱检测分析技术的基础上,以小鼠BALB/c 3T3细胞两阶段转化实验为模型,对比研究了3种促癌物(TPA、OA、CdCl_2)诱导的转化细胞集落基因表达谱,为识别细胞转化相关基因和促癌物特征性基因表达提供实验依据和进一步深入研究的线索;同时分析3种促癌物在作用过程中对基因表达的影响,以初步探讨促癌作用相关的分子机理。研究内容包括四个部分:(1) BALB/c 3T3细胞两阶段转化实验模型的建立;(2) 小鼠毒理基因芯片制作和检测方法的建立;(3) 不同促癌物诱导的BALB/c 3T3转化细胞集落的基因表达谱分析;(4) 不同促癌物促进BALB/c3T3细胞转化过程中的基因表达谱分析。主要结果如下:
1.本课题以MNNG为启动剂,TPA、OA、CdCl_2分别为促癌剂,建立了两阶段BALB/c 3T3细胞转化模型。1μg/ml MNNG或高剂量组促癌物单独作用均不能诱导细胞转化,而MNNG启动后,分别使用TPA、OA、CdCl_2则能显著提高细胞转化率,并存在剂量反应关系,表明TPA、OA和CdCl_2在细胞转化过程中发挥促癌作用。同时分别挑选培养的不同促癌物诱导的转化细胞集落经软琼脂生长测试,均具有锚着不依赖生长特性。
It is general realized that the progress of cancer caused by chemicals is a long time, multistage, multi-gene and multi-pathogeny. The multistage carcinogenesis is involved with three steps including initiation, promotion and progression, and chemical carcinogens influence tumor development in many ways by acting as initiators, promoters or progressors, while the tumor promoters play a major role in the multistage carcinogenesis. It has long been elucidated that the tumor promoters can induce tumor development in previously initiated cells by causing their selective expansion, and this effect is reversible at the early time of tumor promotion, thus early studies on the identification and inhibition of the effects of tumor promoters have presaged modern chemoprevention in humans. On the other hand, Toxicologists employ a battery of tests to identify chemicals with potential carcinogenicity and these methods have been proved to be costly and labor intensive. It is apparent that alternative testing approaches must be developed to improve the identification of potential carcinogens including tumor-promoting agents. Additionally, the mechanisms of actions of tumor promotes are poorly understood, in a general sense, it is promised that the mechanisms of tumor promotion are also involved with multiple genes and signalling pathways, more and more genes have been found to play major role in this process, thus it is not effective to address the complex mechanism of tumor-promoting action with traditional expression-based technologies, such as northern blots, in situ hybridization or RNase protection assays, which examine gene expression changes for only a few genes at a time.cDNA chip technology, which can be used to analyze changes in genome-wide patterns of gene expression, is a new methodological advance that may revolutionize the way of investigations for some toxicological problems, such as carcinogenesis. This technology enable the simultaneous monitoring of thousands of genes expression changes in one experiment, it will be useful to identify the characteristic gene expression patterns, what so called gene fingerprint, for specific toxicant or carcinogen. The potential uses of gene chip in toxicology involve to identify chemicals of the basis of tissue specific patterns of gene expression by establishing molecular signature for chemical exposure, and to elucidate the
mechanisms of action of environmental agents through the identification of gene expression network. Till now, some investigations have already proved that the gene chip technology could be successfully applied to detect and identify the specific gene expression of potential carcinogens, that also indicates this technology will be useful in the investigation of tumor promotion. In order to find out clues for further identifying the genes related to cell transformation and the characteristic gene expression patterns reflected specific tumor promoter(TPA, OA or CdCl2), nine clones induced by MNNG and different tumor promoter in the two-stage BALB/c 3T3 cell transformation test were used to detect the gene expression profiles with mouse toxicology gene chips. Besides, for understanding the molecular mechanisms of the cell transformation promoted with tumor promoters(TPA, OA or CdCia), cells treated with different tumor promoter in the two-stage BALB/c 3T3 cell transformation test were harvested in each time point during the promotion stage, and gene expression profiles were detected with mouse toxicology gene chips. This experimental study was composed of four parts: (1) Establishing the in vitro two-stage BALB/c 3T3 cells transformation test with MNNG as initiator, TPA, OA or CdC^ as promoter respectively; (2) Establishing and evaluating the technique of fabrication and detection for mouse toxicology gene chip; (3) Analysis of gene expression profiles for transformed cell clones induced by different tumor promoter; (4) Analysis of gene expression profiles for BALB/c 3T3 cells treated with different tumor promoter during the promotion stage. The main results were summed up as follows:1. The two-stage transformation test of BALB/c 3T3 cells were established with MNNG as initiator, TPA, OA or CdCl2 as promoter respectively. The promoters significantly enhanced the transformation of cells initiated with ll^g/ml MNNG, whereas high dose promotes failed to induce transformation without pretreatment of MNNG At the same time, nine clones transformed with MNNG and different promoter were choosed and cultured for the further investigation, and all these clones had the character of anchorage-independent growth in soft agar tests.2. 1796 genes related to eight biological functions were choosed for the construction of the mouse toxicology gene chip, and the corresponding database was established at the same time. Preliminary investigations indicated this toxicology chip designed by ourselves could applied in the identification and evaluation for toxicant actions including tumor promoting effect.
3.The gene fragments used to fabricate the gene chip were copied from NIA mouse cDNA clone sets, and the result of gene fragments proliferation showed that 95.12% of the PCR products had strong and single band. Moreover, five batches of slides had good images in the selective examination with Picogreen dye method. These results indicated that the proliferation of target genes and the fabrication of chips had been fulfilled successfully.4. Preliminary toxicological tests proved the validity of the chip hybridization and detection technology established in our lab according to the reference, and the effectivity of the locally mean normalization method to analyze the original data.5. Several methods were applied to verify the reliability and reproducibility of the gene chip data. The results showed that there was no nonspecific hybridization in the negative control spots; Good reproducibility could achieved among the repetitive genes in a chip; Different batches of chips had instant quality and reproducibility; Dye swap labeling had advantages in reducing the dye errors; Finally the real-time RT-PCR method validated most of the data come from chip hybridization. These results proved the accuracy of the gene chip data.6. Gene expression profiles of transformed clones induced by different promoter were screened with mouse toxicology gene chips. 236 genes were found to differentially expressed in nine transformed clones compared with normal cells, and the classification of gene functions indicated that the largest three functional gene groups of each transformed clone were involved with cell growth/maintenance, signal transduction, transcriptional regulation or metablism.7. 236 differentially expressed genes in the transformed clones were hierarchically clustered and nine transformed clones were separated into three main branches in concordance with the promoter used to induce them. The result suggested that transformed clone maybe has specific tumor promoter-associated gene expression profile.8. Two clusters of genes showed similar expression patterns among all of the transformed clones, one cluster consisted genes up-regulated(23), and the other cluster consisted genes down-regulated(26). The expression change of these genes suggested a possibility that they may play a role in the cell transformation.9. Several clusters of genes showed characteristic expression patterns that highlighted the differences among the different promoter induced transformed clones. One cluster consisted 6 genes up-regulated in TPA-induced clones, one cluster consisted 14 genes up-regulated in
OA-induced clones, and the other cluster consisted 18 genes up-regulated in CdCl2-induced clones. These genes differentially expressed among different promoter induced clones were expected to be related with the molecular mechanisms specific to a promoter.10. Gene expression profiles of cells treated with different promoter during the promotion stage of BLAB/c 3T3 cells transformation test were detected with mouse toxicology gene chip. The numbers of differentially expressed genes influenced by each promoter were 120 in TPA, 177 in OA and 139 in CdCl2, and the classification of gene functions showed that the largest functional gene group induced by each promoter was similar and involved with cell growth/maintenance. Combined with previous result of cell growth curve, these results suggested that the promoting effects of TPA, OA and CdC^ in the early time of promotion are related to cell growth arrest or apoptosis induction.11. Further analysis for the functions of differentially expressed genes involved with cell proliferation or apoptosis suggested the possibilities that TPA could influence the transcriptional expression of some genes mainly related to the ras and P53 signal transduction pathways and ultimatedly result in the cell growth arrest, and the possibility of apoptosis induction also exists. In addition, OA could influence the expression of genes mainly related to the mitochondrial apoptosis pathway and then induce cell apoptosis. while CdCh could influence the expression of genes related to mitochondrial apoptosis pathway and Fas-ligand apoptosis pathway simultaneously and then induce cell apoptosis.12. A group of genes related to the antioxidation were differentially expressed after the treatment of TPA, OA or CdCl2. This result suggested the possibility that during the promotion stage, promoter could cause the unbalance between oxidation and antioxidation in cells, and the created reactive oxygen species may act as secondary messengers to initiate the apoptosis.13. There were same differentially expressed genes induced by TPA, OA and CdCl2, among these genes, SPP1 was up-regulated mainly in the middle and late stage of promotion. Functional analysis indicates that SPP1 mediates tumor metastasis and invasion, funcions in the regulation of cell cycle progression and prevention of apoptosis.
毒理基因组学的出现引导研究者从基因组角度进行毒理研究,基因芯片技术因为具有高通量平行处理的特点而成为毒理基因组研究的主要工具。基因芯片表达谱分析能实现对成千上万个基因表达的平行检测,易于发现化合物的特征性表达变化,因而在对包括致癌物在内的毒物检测识别和作用机理研究方面有了越来越广泛的应用,这提示此技术也能有效用于促癌物的检测识别和促癌作用机理的研究。因此,本课题在建立小鼠毒理基因芯片表达谱检测分析技术的基础上,以小鼠BALB/c 3T3细胞两阶段转化实验为模型,对比研究了3种促癌物(TPA、OA、CdCl_2)诱导的转化细胞集落基因表达谱,为识别细胞转化相关基因和促癌物特征性基因表达提供实验依据和进一步深入研究的线索;同时分析3种促癌物在作用过程中对基因表达的影响,以初步探讨促癌作用相关的分子机理。研究内容包括四个部分:(1) BALB/c 3T3细胞两阶段转化实验模型的建立;(2) 小鼠毒理基因芯片制作和检测方法的建立;(3) 不同促癌物诱导的BALB/c 3T3转化细胞集落的基因表达谱分析;(4) 不同促癌物促进BALB/c3T3细胞转化过程中的基因表达谱分析。主要结果如下:
1.本课题以MNNG为启动剂,TPA、OA、CdCl_2分别为促癌剂,建立了两阶段BALB/c 3T3细胞转化模型。1μg/ml MNNG或高剂量组促癌物单独作用均不能诱导细胞转化,而MNNG启动后,分别使用TPA、OA、CdCl_2则能显著提高细胞转化率,并存在剂量反应关系,表明TPA、OA和CdCl_2在细胞转化过程中发挥促癌作用。同时分别挑选培养的不同促癌物诱导的转化细胞集落经软琼脂生长测试,均具有锚着不依赖生长特性。
It is general realized that the progress of cancer caused by chemicals is a long time, multistage, multi-gene and multi-pathogeny. The multistage carcinogenesis is involved with three steps including initiation, promotion and progression, and chemical carcinogens influence tumor development in many ways by acting as initiators, promoters or progressors, while the tumor promoters play a major role in the multistage carcinogenesis. It has long been elucidated that the tumor promoters can induce tumor development in previously initiated cells by causing their selective expansion, and this effect is reversible at the early time of tumor promotion, thus early studies on the identification and inhibition of the effects of tumor promoters have presaged modern chemoprevention in humans. On the other hand, Toxicologists employ a battery of tests to identify chemicals with potential carcinogenicity and these methods have been proved to be costly and labor intensive. It is apparent that alternative testing approaches must be developed to improve the identification of potential carcinogens including tumor-promoting agents. Additionally, the mechanisms of actions of tumor promotes are poorly understood, in a general sense, it is promised that the mechanisms of tumor promotion are also involved with multiple genes and signalling pathways, more and more genes have been found to play major role in this process, thus it is not effective to address the complex mechanism of tumor-promoting action with traditional expression-based technologies, such as northern blots, in situ hybridization or RNase protection assays, which examine gene expression changes for only a few genes at a time.cDNA chip technology, which can be used to analyze changes in genome-wide patterns of gene expression, is a new methodological advance that may revolutionize the way of investigations for some toxicological problems, such as carcinogenesis. This technology enable the simultaneous monitoring of thousands of genes expression changes in one experiment, it will be useful to identify the characteristic gene expression patterns, what so called gene fingerprint, for specific toxicant or carcinogen. The potential uses of gene chip in toxicology involve to identify chemicals of the basis of tissue specific patterns of gene expression by establishing molecular signature for chemical exposure, and to elucidate the
mechanisms of action of environmental agents through the identification of gene expression network. Till now, some investigations have already proved that the gene chip technology could be successfully applied to detect and identify the specific gene expression of potential carcinogens, that also indicates this technology will be useful in the investigation of tumor promotion. In order to find out clues for further identifying the genes related to cell transformation and the characteristic gene expression patterns reflected specific tumor promoter(TPA, OA or CdCl2), nine clones induced by MNNG and different tumor promoter in the two-stage BALB/c 3T3 cell transformation test were used to detect the gene expression profiles with mouse toxicology gene chips. Besides, for understanding the molecular mechanisms of the cell transformation promoted with tumor promoters(TPA, OA or CdCia), cells treated with different tumor promoter in the two-stage BALB/c 3T3 cell transformation test were harvested in each time point during the promotion stage, and gene expression profiles were detected with mouse toxicology gene chips. This experimental study was composed of four parts: (1) Establishing the in vitro two-stage BALB/c 3T3 cells transformation test with MNNG as initiator, TPA, OA or CdC^ as promoter respectively; (2) Establishing and evaluating the technique of fabrication and detection for mouse toxicology gene chip; (3) Analysis of gene expression profiles for transformed cell clones induced by different tumor promoter; (4) Analysis of gene expression profiles for BALB/c 3T3 cells treated with different tumor promoter during the promotion stage. The main results were summed up as follows:1. The two-stage transformation test of BALB/c 3T3 cells were established with MNNG as initiator, TPA, OA or CdCl2 as promoter respectively. The promoters significantly enhanced the transformation of cells initiated with ll^g/ml MNNG, whereas high dose promotes failed to induce transformation without pretreatment of MNNG At the same time, nine clones transformed with MNNG and different promoter were choosed and cultured for the further investigation, and all these clones had the character of anchorage-independent growth in soft agar tests.2. 1796 genes related to eight biological functions were choosed for the construction of the mouse toxicology gene chip, and the corresponding database was established at the same time. Preliminary investigations indicated this toxicology chip designed by ourselves could applied in the identification and evaluation for toxicant actions including tumor promoting effect.
3.The gene fragments used to fabricate the gene chip were copied from NIA mouse cDNA clone sets, and the result of gene fragments proliferation showed that 95.12% of the PCR products had strong and single band. Moreover, five batches of slides had good images in the selective examination with Picogreen dye method. These results indicated that the proliferation of target genes and the fabrication of chips had been fulfilled successfully.4. Preliminary toxicological tests proved the validity of the chip hybridization and detection technology established in our lab according to the reference, and the effectivity of the locally mean normalization method to analyze the original data.5. Several methods were applied to verify the reliability and reproducibility of the gene chip data. The results showed that there was no nonspecific hybridization in the negative control spots; Good reproducibility could achieved among the repetitive genes in a chip; Different batches of chips had instant quality and reproducibility; Dye swap labeling had advantages in reducing the dye errors; Finally the real-time RT-PCR method validated most of the data come from chip hybridization. These results proved the accuracy of the gene chip data.6. Gene expression profiles of transformed clones induced by different promoter were screened with mouse toxicology gene chips. 236 genes were found to differentially expressed in nine transformed clones compared with normal cells, and the classification of gene functions indicated that the largest three functional gene groups of each transformed clone were involved with cell growth/maintenance, signal transduction, transcriptional regulation or metablism.7. 236 differentially expressed genes in the transformed clones were hierarchically clustered and nine transformed clones were separated into three main branches in concordance with the promoter used to induce them. The result suggested that transformed clone maybe has specific tumor promoter-associated gene expression profile.8. Two clusters of genes showed similar expression patterns among all of the transformed clones, one cluster consisted genes up-regulated(23), and the other cluster consisted genes down-regulated(26). The expression change of these genes suggested a possibility that they may play a role in the cell transformation.9. Several clusters of genes showed characteristic expression patterns that highlighted the differences among the different promoter induced transformed clones. One cluster consisted 6 genes up-regulated in TPA-induced clones, one cluster consisted 14 genes up-regulated in
OA-induced clones, and the other cluster consisted 18 genes up-regulated in CdCl2-induced clones. These genes differentially expressed among different promoter induced clones were expected to be related with the molecular mechanisms specific to a promoter.10. Gene expression profiles of cells treated with different promoter during the promotion stage of BLAB/c 3T3 cells transformation test were detected with mouse toxicology gene chip. The numbers of differentially expressed genes influenced by each promoter were 120 in TPA, 177 in OA and 139 in CdCl2, and the classification of gene functions showed that the largest functional gene group induced by each promoter was similar and involved with cell growth/maintenance. Combined with previous result of cell growth curve, these results suggested that the promoting effects of TPA, OA and CdC^ in the early time of promotion are related to cell growth arrest or apoptosis induction.11. Further analysis for the functions of differentially expressed genes involved with cell proliferation or apoptosis suggested the possibilities that TPA could influence the transcriptional expression of some genes mainly related to the ras and P53 signal transduction pathways and ultimatedly result in the cell growth arrest, and the possibility of apoptosis induction also exists. In addition, OA could influence the expression of genes mainly related to the mitochondrial apoptosis pathway and then induce cell apoptosis. while CdCh could influence the expression of genes related to mitochondrial apoptosis pathway and Fas-ligand apoptosis pathway simultaneously and then induce cell apoptosis.12. A group of genes related to the antioxidation were differentially expressed after the treatment of TPA, OA or CdCl2. This result suggested the possibility that during the promotion stage, promoter could cause the unbalance between oxidation and antioxidation in cells, and the created reactive oxygen species may act as secondary messengers to initiate the apoptosis.13. There were same differentially expressed genes induced by TPA, OA and CdCl2, among these genes, SPP1 was up-regulated mainly in the middle and late stage of promotion. Functional analysis indicates that SPP1 mediates tumor metastasis and invasion, funcions in the regulation of cell cycle progression and prevention of apoptosis.
引文
1.李寿祺主编.《毒理学原理与方法》第2版.四川成都:四川大学出版社.2003:182-190.
2. Berenblum I. A re-evaluation of the concept of cocarciongenesis. Prog Exp Tumor Res. 1969;11:21-30.
3. Goerttler K, Loehrke H. Diaplacental carcinogenesis: initiation with the carcinogens dimethylbenzanthracene (DMBA) and urethane during fetal life and postnatal promotion with the phorbol ester TPA in a modified 2-stage Berenblum/Mottram experiment. Virchows Arch A Pathol Anat Histol. 1976; 372(1):29-38.
4. Welsch CW, Nagasawa H. Prolactin and murine mammary tumorigenesis: a review. Cancer Res. 1977; 37(4):951-963.
5. Hirst GL, Balmain A. Forty years of cancer modelling in the mouse. Eur J Cancer. 2004;40(13):1974-1980
6.夏世均,吴中亮主编.《分子毒理学基础》.武汉:湖北科学技术出版社.2001:118-119
7. Turosov VS. Progression of tumors: etiologic, morphologic and molecular-biological aspects. Arkh Patol. 1992;54(7):5-14
8. Hennings H, Lowry DT, Robinson VA, et al. Activity of diverse tumor promoters in a keratinocyte co-culture model of initiated epidermis. Carcinogenesis. 1992; 13(11): 2145-2151
9. Slaga TJ, Budunova Ⅳ, Gimenez-Conti IB, et al. The mouse skin carcinogenesis model. J Investig Dermatol Symp Proc. 1996;1(2):151-156
10. Pitot HC, Dragan YP, Teeguarden J, et al. Quantitation of multistage carcinogenesis in rat liver. Toxicol Pathol. 1996;24(1):119-128
11. Pitot HC, Hikita H, Dragan Y, et al. Review article: the stages of gastrointestinal carcinogenesis—application of rodent models to human disease. Aliment Pharmacol Ther. 2000;14 Suppl 1:153-160
12. Trosko JE. Commentary: is the concept of "tumor promotion" a useful paradigm? Mol Carcinog. 2001 ;30(3): 131-137
13. Pretlow TG, Nagabhushan M, Sy M, et al. Putative preneoplastic foci in the human prostate. J Cell Biochem Suppl. 1994; 19:224-231
14.付立杰主编.《现代毒理学及其应用》.上海:上海科学技术出版社.2001:112-115
15. Owens DM, Wei S, Smart RC. A multihit, multistage model of chemical carcinogenesis. Carcinogenesis. 1999;20(9):1837-1844
16. Pitot HC, Goldsworthy TL, Moran S, et al. A method to quantitate the relative initiating and promoting potencies of hepatocarcinogenic agents in their dose-response relationships to altered hepatic foci. Carcinogenesis. 1987;8(10):1491-1499
17. Hikita H, Vaughan J, Babcock K, et al. Short-term fasting and the reversal of the stage of promotion in rat hepatocarcinogenesis: role of cell replication, apoptosis, and gene expression. Toxicol Sci. 1999;52(2 Suppl):17-23
18. Young MR, Yang HS, Colburn NH. Promising molecular targets for cancer prevention: AP-1, NF-kappa B and Pdcd4. Trends Mol Med. 2003;9(1):36-41
19. Chen ZH, Hurh YJ, Na HK, et al. Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells. Carcinogenesis. 2004;25(10):2005-2013.
20. Schulte-Hermann R, Bursch W, Marian B, et al. Active cell death (apoptosis) and cellular proliferation as indicators of exposure to carcinogens. IARC Sci Publ. 1999;(146):273-85
21.印木泉主编.《遗传毒理学》.北京:科学出版社.2002:268-273
22. Cochet C, Keramidas M, Souvignet C, et al. Phorbol ester-induced alteration of protein kinase C catalytic properties occurs at the membrane level and is not reproduced by physiological stimuli. Biochem Biophys Res Commun. 1986 14;138(3):1283-1290
23.夏世均,吴中亮主编.《分子毒理学基础》.武汉:湖北科学技术出版社.2001:135
24. Pitot HC. Endogenous carcinogenesis: the role of tumor promotion. Proc Soc Exp Biol Med. 1991; 198(2):661-666
25. Williams GM, Iatropoulos MJ, Whysner J. Safety assessment of butylated hydroxyanisole and butylated hydroxytoluene as antioxidant food additives.. Food Chem Toxicol. 1999;37(9-10):1027-1038
26. Lok E, Nera EA, Iverson F, et al. Dietary restriction, cell proliferation and carcinogenesis: a preliminary study. Cancer Lett. 1988;38(3):249-255
27. Weisburger JH. Hazards of fast food. Environ Health Perspect. 2004; 112(6):A336
28. Teeguarden JG, Newton MA, Dragan YP, et al. Genome-wide loss of heterozygosity analysis of chemically induced rat hepatocellular carcinomas reveals elevated frequency of allelic imbalances on chromosomes 1, 6, 8, 11, 15, 17, and 20. Mol Carcinog. 2000;28(1):51-6
29. Ashendel CL, Staller JM, Boutwell RK. Identification of a calcium- and phospholipid- dependent phorbol ester binding activity in the soluble fraction of mouse tissues. Biochem Biophys Res Commun. 1983;111(1):340-345
30. Wheeler DL, Ness KJ, Oberley TD, et al. Inhibition of the development of metastatic squamous cell carcinoma in protein kinase C epsilon transgenic mice by alpha-difluoromethylornithine accompanied by marked hair follicle degeneration and hair loss. Cancer Res. 2003;63(12):3037-3042
31. Lee RG, Rosson D. 12-O-tetradecanoylphorbol-13-acetate induces apoptosis in renal epithelial cells through a growth signal conflict which is prevented by activated ras. Arch Biochem Biophys. 2001;385(2):378-386
32. Patel KV, Schrey MP. Evidence for a role for protein kinase C in the modulation of bombesin-activated cellular signalling in human breast cancer cells. Mol Cell Endocrinol. 1992;85(3):215-225
33. Fujiki H, Suganuma M, Okabe S, et al.A new concept of tumor promotion by tumor necrosis factor-alpha, and cancer preventive agents (-)-epigallocatechin gallate and green tea-a review. Cancer Detect Prev. 2000;24(l):91-99
34. Olden K, Guthrie J. Genomics: implications for toxicology. Mutat Res. 2001; 473(1):3-10
35. Aardema MJ, MacGregor JT. Toxicology and genetic toxicology in the new era of "toxicogenomics": impact of "-omics" technologies. Mutat Res. 2002;499(1): 13-25
36. Schena M, Heller RA, Theriault TP, et al.Microarrays: biotechnology's discovery platform for functional genomics. Trends Biotechnol. 1998;16(7):301-306
37. Afshari CA, Nuwaysir EF, Barrett JC. Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation. Cancer Res. 1999;59(19):4759-4760
38. Nuwaysir EF, Bittner M, Trent J, et al. Microarrays and toxicology: the advent of
toxicogenomics. Mol Carcinog. 1999;24(3):153-159
39. Fa4r S, Dunn RT. Concise review: gene expression applied to toxicology. Toxicol. Sci. 1999;50(1):1-9
40. Morgan KT. Gene Expression Analysis Reveals Chemical-Specific Profiles. Toxicol Sci. 2002;67(2):155-156
41. Jeong JS, Lee SH, Jung KJ, et al. Hepatotoxin N-nitrosomorpholine-induced carcinogenesis in rat liver: ex vivo exploration of preneoplastic and neoplastic hepatocytes. Exp Mol Pathol. 2003;74(1):74-83
42. Pole JC, Gold LI, Orton T, et al. Gene expression changes induced by estrogen and selective estrogen receptor modulators in primary-cultured human endometrial cells: signals that distinguish the human carcinogen tamoxifen. Toxicology. 2005 5;206(1):91-109
43. Harris AJ, Dial SL, Casciano DA. Comparison of basal gene expression profiles and effects of hepatocarcinogens on gene expression in cultured primary human hepatocytes and HepG2 cells. Mutat Res. 2004;549(l-2):79-99
44. Ye J, Shi X. Gene expression profile in response to chromium-induced cell stress in A549 cells. Mol Cell Biochem. 2001;222(1-2):189-197
45. Lee M, Kwon J, Kim SN, et al. cDNA microarray gene expression profiling of hydroxyurea, paclitaxel, and p-anisidine, genotoxic compounds with differing tumorigenicity results. Environ Mol Mutagen. 2003 ;42(2):91-7
46. Schlingemann J, Hess J, Wrobel G, et al. Profile of gene expression induced by the tumour promotor TPA in murine epithelial cells. Int J Cancer. 2003;104(6):699-708
47. Wei SJ, Trempus CS, Cannon RE, et al. Identification of Dssl as a 12-O-tetradecanoylphorbol-13-acetate-responsive gene expressed in keratinocyte progenitor cells, with possible involvement in early skin tumorigenesis. J Biol Chem. 2003;278(3):1758-1768
48. Dhar A, Hu J, Reeves R, et al. Dominant-negative c-Jun (TAM67) target genes: HMGA1 is required for tumor promoter-induced transformation. Oncogene. 2004;23(25):4466-4476
49. Samuel S, Bernstein LR. Adhesion, migration, transcriptional, interferon-inducible, and other signaling molecules newly implicated in cancer susceptibility and resistance
of JB6 cells by cDNA microarray analyses. Mol Carcinog. 2004;39(1):34-60
50. Chan CY, Salabat MR, Ding XZ, et al. Identification and in silico characterization of a novel gene: TPA induced trans-membrane protein. Biochem Biophys Res Commun. 2005 ;329(2):755-764
51. http://ntp-server.niehs.nih.gov/
52. Ashby J, Tennant RW. Definitive relationships among chemical structure, carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat Res. 1991; 257(3): 229-306
53. Dunkel,VC, Rogers C, Swierenga SH, et al. Recommended protocols based on a survey of current practice in genotoxicity testing laboratories: Ⅲ. Cell transformation in C3H/10T1/2 mouse. Mutat. Res. 1991; 246(2): 285-300
54. Matthews EJ, Spalding JW, Tennant RW. Transformation of BALB/c-3T3 cells: Ⅴ. Transformation responses of 168 chemicals compared with mutagenicity in Salmonella and carcinogenicity in rodent bioassays. Environ Health Perspect. 1993;101 Suppl 2:347-482
55. IARC/NCI/EPA Working Group. Cellular and molecular mechanisms of cell transformation and standardization of transformation assays of established cell lines for the prediction of carcinogenic chemicals: overview and recommended protocols. Cancer Res. 1985,45:2395-2399
56. Fang MZ, Kim DY, Lee HW, et al. Improvement of in vitro two-stage transformation assay and determination of the promotional effect of cadmium. Toxicol In Vitro. 2001; 15 (3):225-231
57. Sakai A, Sato M. Improvement of carcinogen identification in BALB/3T3 cell transformation by application of a 2-stage method. Mutat Res. 1989;214(2):285-296.
58.敖琳,曹佳,黄明辉等.佛波酯对BALB/c 3T3细胞转化早期基因表达的影响.中华预防医学杂志.2005:39(2):99-102
59.沈建英,蒋芸,张招弟等.致癌物鉴定方法的现况及展望.中国公共卫生学报.1996;15(6):35-38
60.鄂征主编.《组织培养和分子细胞学技术》.北京出版社.1999.:223-224
61. Todaro GJ, Aaronson SA. Properties of clonal lines of murine sarcoma virus transformed Balb-3T3 cells. Virology. 1969; 38(1): 174-179
62. Aaronson SA, Todaro GJ. Development of 3T3-1ike lines from Balb-c mouse embryo cultures: transformation susceptibility to SV40. J Cell Physiol. 1968; 72(2): 141-148
63. Schechtman LM. BALB/c 3T3 cell transformation: protocols, problems and improvements. IARC Sci Publ. 1985; 67:165-184
64. M Bignami, E Dogliotti, R. Benigni, et al. Split-dose exposure to N-methyl-N'-nitro-N-nitrosoguanidine in BALB/3T3 C1 A31-1-1 cells: Evidence of DNA repair by alkaline elution without changes in cell survival, mutation and transformation rates. Mutat Res. 1985 145(1-2): 81-88.
65. Sakai A, Fujiki H. Promotion of BALB/3T3 cell transformation by the okadaic acid class of tumor promoters, okadaic acid and dinophysistoxin-1. Jpn J Cancer Res. 1991; 82(5): 518-523
66. Katoh F, Fitzgerald DJ, Giroldi L, et al. Okadaic acid and phorbol esters: comparative effects of these tumor promoters on cell transformation, intercellular communication and differentiation in vitro. Jpn J Cancer Res. 1990; 81(6-7): 590-597
67. Tsuchiya T; Umeda M. Relationship between exposure to TPA and appearance of transformed cells in MNNG-initiated transformation of BALB/c 3T3 cells. Int J Cancer. 199; 73(2): 271-276
68. Sakai A. Orthovanadate, an inhibitor of protein tyrosine phosphatases, acts more potently as a promoter than as an initiator in the BALB/3T3 cell transformation. Carcinogenesis. 1997;18(7):1395-1399
69. Landolph JR. Mechanisms of chemically induced multistep neoplastic transformation in C3H 10T 1/2 cells. Carcinog Compr Surv. 1985;10:211-223
70. Reznikoff CA, Bertram JS, Brankow DW, et al. Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of. Cancer Reso 1973; 33(12): 3239-3249
71. Smith GJ, Bell WN, Grisham JW. Clonal analysis of the expression of multiple transformation phenotypes and tumorigenicity by morphologically transformed 10T1/2 cells. Cancer Res. 1993 ; 53(3): 500-508
72. Keshava N. Tumorigenicity of morphologically distinct transformed loci induced by 3-methylcholanthrene in BALB/c-3T3 cells. Mutat Res. 2000; 447(2): 281-286
73.郭仁,张和君,董德详等主编.《分子细胞生物学》.北京医科大学,中国协和医科大 学联合出版社.1995:342-343
74. Wei SJ, Trempus CS, Ali RC, et al. 12-O-Tetradecanoylphorbol-13-acetate and UV Radiation-induced Nucleoside Diphosphate Protein Kinase B Mediates Neoplastic Transformation of Epidermal Cells. J Biol Chem. 2004; 279(7): 5993-6004
75. Tsuchiya T, Umeda M. Improvement in the efficiency of the in vitro transformation assay method using BALB/3T3 A31-1-1 cells. Carcinogenesis. 1995;16(8): 1887-1894
76. Fujimura S, Kogure K, Oboshi S, et al. Production of tumors in glandular stomach of hamsters by N-methyl-N'-nitro-N-nitrosoguanidine. Cancer Res. 1970;30(5): 1444-1448
77. Niknahad H, O'Brien PJ. Cytotoxicity induced by N-methyl-N'-nitro-N-nitrosoguanidine may involve S-nitrosyl glutathione and nitric oxide. Xenobiotica. 1995; 25(1): 91-101
78.冯朝晖,余应年,陈星若等.甲基硝基亚硝基胍诱发的遗传不稳定vero细胞DNA体外复制的保真度.中国药理学与毒理学杂志.1998;(2):144-148
79. Fang MZ, Mar WC, Cho MH. Cell cycle was disturbed in the MNNG-induced initiation stage during in vitro two-stage transformation of Balb/3T3 cells. Toxicology. 2001; 163(2-3): 175-184
80. Edara S, Kanugula S, Pegg AE. Expression of the inactive C145A mutant human O6-alkylguanine-DNA alkyltransferase in E.coli increases cell killing and mutations by N-methyl-N'-nitro-N-nitrosoguanidine. Carcinogenesis. 1999; 20(1): 103-108
81. Tominaga Y, Tsuzuki T, Shiraishi A, et al. Alkylation-induced apoptosis of embryonic stem cells in which the gene for DNA-repair, methyltransferase, had been disrupted by gene targeting. Carcinogenesis. 1997; 18(5): 889-896
82. Jelinsky SA, Samson LD. Global response of Saccharomyces cerevisiae to an alkylating agent. Proc Natl Acad Sci. 1999 96(4): 1486-1491
83. Marczynska B, Khoobyarian N, Chao TS, et al. Phorbol ester promotes growth and transformation of carcinogen-exposed nonhuman primate cells in vitro. Anticancer-Res. 1991; 11(5): 1711-1717
84. Adolf W, Hecker E. On the active principles of the spurge family. Ⅲ. Skin irritant and cocarcinogenic factors from the caper spurge. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1975;84(3):325-344
85. Cochet C, Souvignet C, Keramidas M, et al. Altered catalytic properties of protein kinase C in phorbol ester treated cells. Biochem Biophys Res Commun. 1986;134(3):1031-1037
86. Cabot MC, Welsh CJ, Cao HT, et al. The phosphatidylcholine pathway of diacylglycerol formation stimulated by phorbol diesters occurs via phospholipase D activation. FEBS-Lett. 1988; 233(1): 153-157
87. Huang XP, Da Silva C, Fan XT, et al.Characteristics of arachidonic-acid-mediated brain protein kinase C activation: evidence for concentration-dependent heterogeneity. Biochim Biophys Acta. 1993 17;1175(3):351-356
88. Basu S, Kolesnick R. Stress signals for apoptosis: ceramide and c-Jun kinase. Oncogene. 1998(25): 3277-3285
89. Rice RH, Steinmann KE, Degraffenried LA, et al. Elevation of cell cycle control proteins during spontaneous immortalization of human keratinocytes. Mol-Biol-Cell. 1993;4(2):185-194
90. Hahn MA, Mayne GC. Phorbol ester-induced cell death in PC-12 cells overexpressing Bcl-2 is dependent on the time at which cells are treated. Cell Biol Int. 2004;28(5):345-359
91. Masuda Y,Yoda M,Ohizumi H, et al. Activation of protein kinase C prevents induction of apoptosis by geranylgeraniol in human leukemia HL60 cells. Int J Cancer. 1997;71(4):691-697
92. Suganuma M, Fujiki H, Suguri H, et al. Okadaic acid: an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter. Proc. Natl. Acad. Sci. USA. 1988;85(6):1768-1771
93. Rajesh D, Schell K, Verma AK. Ras Mutation, Irrespective of Cell Type and p53 Status, Determines a Cell's Destiny to Undergo Apoptosis by Okadaic Acid, an Inhibitor of Protein Phosphatase 1 and 2A. Mol Pharmacol 1999 56(3): 515-525
94. Mordan LJ, Dean NM, Honkanen RE, et al. Okadaic acid: a reversible inhibitor of neoplastic transformation of mouse fibroblasts. Cancer Commun. 1990;2(7):237-241
95. Rivedal E, Mikalsen SO, Sanner T. The non-phorbol ester tumor promoter okadaic acid does not promote morphological transformation or inhibit junctional
communication in hamster embryo cells. Biochem Biophys Res Commun. 1990;167(3):1302-1308
96. Gupta RW, Joseph CK, Foster DA. v-Src-induced transformation is inhibited by okadaic acid. Biochem Biophys Res Commun. 1993; 196(1): 320-327
97. Sheu CW, Rodriguez I, Dobras SN, et al. Induction of morphological transformation in BALB/3T3 mouse embryo cells by okadaic acid. Food Chem Toxicol. 1995;33(10):883-885
98. Aonuma S, Ushijima T, Nakayasu M, et al. Mutation induction by okadaic acid, a protein phosphatase inhibitor, in CHL cells, but not in S. typhimurium. Mutat Res. 1991; 250(1-2): 375-381
99. Waalkes MP. Cadmium carcinogenesis. Mutat Res. 2003, 533(l-2):107-120
100. Waalkes MP, Coogan TP, Barter RA. Toxicological principles of metal carcinogenesis with special emphasis on cadmium. Crit Rev Toxicol. 1992;22(3-4): 175-201
101. Achanzar WE., Diwan BA, et al. Cadmium-induced Malignant Transformation of Human Prostate Epithelial Cells. Cancer Res 2001;61:455-458
102. Nakamura K, Yasunaga Y, Ko D, et al. Cadmium-induced neoplastic transformation of human prostate epithelial cells. Int J Oncol. 2002;20(3): 543-547
103. Misra RR, Smith GT, Waalkes MP. Evaluation of the direct genotoxic potential of cadmium in four different rodent cell lines. Toxicology. 1998;126(2):103-114
104. Keshava N, Zhou G, Hubbs AF, et al. Transforming and carcinogenic potential of cadmium chloride in BALB/c-3T3 cells. Mutat Res. 2000; 448(1): 23-28
105. Fang MZ, Mar W, Cho MH. Cadmium affects genes involved in growth regulation during two-stage transformation of Balb/3T3 cells. Toxicology. 2002; 177(2-3): 253-265
106. Beyersmann D, Hechtenberg S. Cadmium, gene regulation, and cellular signalling in mammalian cells. Toxicol Appl Pharmacol. 1997;144(2): 247-261
107. Joseph P, Lei YX, Whong WZ, et al. Molecular cloning and functional analysis of a novel cadmium-responsive proto-oncogene. Cancer Res. 2002;62(3): 703-707
108. Yamada H, Koizumi S. DNA microarray analysis of human gene expression induced by a non-lethal dose of cadmium. Ind Health. 2002;40(2):159-166
109. Fodor SP, Read JL, Pirrung MC, et al. Light-directed, spatially addressable parallel
chemical synthesis. Science. 1991; 251(4995): 767-773
110. Schena M, Shalon D, Davis RW, et al. Quantitative monitoring of gene expression pattems with a complementary DNA microarray. Science. 1995;270(5235):467-470
111.陈永忠,谭晓风.基因芯片技术及其应用前景.中南林学院学报.2003;23(4):100-106
112. Graves DJ. Powerful tools for genetic analysis come of age. Trends Biotechnol. 1999; 17(3): 127-134
113. Lipshutz R, Fodor S , Gingeras T, et al. High desity synthetic oligonucleotide arrays. Nature Gentics supplement. 1999;21:20-24.
114. Halgren RG, Fielden MR, Fong CJ, et al. Assessment of clone identity and sequence fidelity for 1189 IMAGE cDNA clones. Nucleic Acids Res 2001;29:582-588.
115. Huang J, Lih CJ, et al. Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways in Streptomyces coelicolor using DNA microarrays. Genes Development. 2001;15:3183-3192
116. Cheung VG, Morley M, Aguilar F, et al. Making and reading microarrays. Nat Genet. 1999;21(1 Suppl) :15-19
117.丁金凤等主编.《基因分析和生物芯片技术》.武汉:湖北科学技术出版社.2004:199-203
118.马立人,蒋中华主编.《生物芯片》.北京:化学工业出版社.2002:170-180
119. Bassett DE, Eisen MB, et al. Gene expression informatics ? it's all in your mine. Nature Genetics Suppl. 1999;21,:51-55
120. http://dir.niehs.nih.gov/microarray/method.htm
121.伍亚舟,张彦琦,黄明辉等.基因芯片表达数据的标准化策略研究.第三军医大学学报.2004;26(7):594-597
122. http://www.affymetrix.com
123. Shioda T. Application of DNA microarray to toxicological research.. J Environ Pat hol Toxicol Oncol. 2004;23(1): 13-31.
124. Wooster R. Cancer classification with DNA microarrays is less more? Trends Genet. 2000; 16(8):327-329
125. Draghici S, Khatri P, Bhavsar P, et al. Onto-Tools, the toolkit of the modem biologist: Onto-Express, Onto-Compare, Onto-Design and Onto-Translate. Nucleic Acids Res. 2003 ;31(13):3775-3781
126. Smith LL. Key challenges for toxicologists in the 21st century. Trends Pharmacol Sci. 2001 ;22(6): 281-285
127. Simmons PT, Portier CJ. Toxicogenomics: the new frontier in risk analysis. Carcinogenesis. 2002; 23(6): 903-905
128. Lacroix M, Zammatteo N, Remacle J, et al. A low-density DNA microarray for analysis of markers in breast cancer. Int J Biol Markers. 2002; 17 (1): 5-23
129. Stears RL, Martinsky T, Schena M. Trends in microar-ray analysis. Nat Med 2003, 1(9): 140-145.
130. Schlaak JF, Hilkens CM, Costa-Pereira AP, et al. Cell-type and Donor-specific Transcriptional Responses to Interferon-α. J. Biol. Chem. 2002; 277(51): 49428-49437
131. http://www.takara.com
132. http://www.phasetox.com
133. http://www.superarray.com
134. Chuaqui RF, Bonner RF, Best CJM, et al. Post-analysis follow-up and validation of icroarray. Experiments. Nat Genet. 2002; 32 suppl:509-514
135.方志俊,曹佳,敖琳.基因芯片分析显示昆明山海棠有机萃取液经NF-κB及线粒体信号传导途径诱导HL-60细胞凋亡.中草药.2003;34(4):334-338
136.罗瑶,许宏,李瑶等.表达谱基因芯片的可靠性验证分析.遗传学报.2003;30(7):611-618
137. Winzeler EA, Schena M, Davis RW. Fluorescence-based expression monitoring using microarrays. Methods-Enzymol. 1999; 306: 3-18
138. Yue H, Eastman PS, Wang BB, et al. An evaluation of the performance of cDNA microarrays for detecting changes in global mRNA expression. Nucleic Acids Res. 2001; 29(8):E41-1
139.马立人,蒋中华主编.《生物芯片》北京:化学工业出版社,2002:6-7
140. Otto WR. Fluorimetric DNA assay of cell number. Methods Mol Biol. 2005; 289:251-262.
141. Yang YH, Speed T. Design issues for cDNA microarray experiments. Nat Rev Genet. 2002; 3(8):579-588
142. J Quackenbush. Microarray data normalization and transformation. Nature Genetics Suppl .2002; 32:496-501
143.范保星,孙敬芬,刘庆峰等.总RNA和MRNA来源的探针与CDNA芯片杂交的差异研究.生物技术通讯.2004;15(1):20-22
144. Hsiao LL, Jensen RV, Yoshida T, et al. Correcting for signal saturation errors in the analysis of microarray data. Biotechniques. 2002;32(2): 330-2, 334, 336
145. Hill AA, Brown EL, Whitley MZ, et al. Evaluation of normalization procedures for oligonucleotide array data based on spiked cRNA controls. Genome Biol. 2001;2(12): RESEARCH0055
146. Tseng GC, Oh MK, Rohlin L, et al. Issues in cDNA microarray analysis: quality filtering, channel normalization, models of variations and assessment of gene effects. Nucleic Acids Res. 2001; 29(12): 2549-2557
147. Yang YH, Dudoit S, Luu P, et al. Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res. 2002; 30(4): el5
148. Hamalainen HK, Tubman JC, Vikman S, et al. Identification and validation of endogenous reference genes for expression profiling of T helper cell differentiation by quantitative real-time RT-PCR. Anal Biochem. 2001;299(1): 63-70
149. Der SD, Zhou A, Williams BR, et al. Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci USA. 1998; 95(26): 15623-15628
150. Hoerndli FJ, Toigo M, Schild A, et al. Reference genes identified in SH-SY5Y cells using custom-made gene arrays with validation by quantitative polymerase chain reaction. Anal Biochem. 2004;335(1):30-41
151. Warrington JA, Nair A, Mahadevappa M, et al. Comparison of human adult and fetal expression and identification of 535 housekeeping/maintenance genes. Physiol Genomics. 2000; 2(3): 143-147
152. Chen H, Liu J, Merrick BA, et al. Genetic events associated with arsenic-induced malignant transformation: applications of cDNA microarray technology. Mol Carcinog. 2001 ;30(2):79-87.
153. Kepler TB, Crosby L, Morgan KT, et al. Normalization and analysis of DNA microarray data by self-consistency and local regression. Genome Biol. 2002; 3(7): research0037.1-research0037.12.
154.顾永清,杨磊,王国荃等.急性砷染毒的L-02细胞的基因芯片分析.西安交通大学学报,2003;24(6):558-560
155. Rosenzweig BA, Pine PS, Domon OE, et al. Dye bias correction in dual-labeled cDNA microarray gene expression measurements. Environ Health Perspect. 2004; 112(4):480-487.
156. Vissers LE, de Vries BB, Osoegawa K, et al. Array-Based Comparative Genomic Hybridization for the Genomewide Detection of Submicroscopic Chromosomal Abnormalities. Am J Hum Genet. 2003;73(6): 1261-1270
157.158. Li Y, Qiu MY, Wu CQ, et al. Detection of differentially expressed genes in hepatocellular carcinoma using DNA microarray. Yi Chuan Xue Bao. 2000; 27(12): 1042-1048.
158. Ueno Y, Alpini G, Yahagi K, et al. Evaluation of differential gene expression by microarray analysis in small and large cholangiocytes isolated from normal mice. Liver Int. 2003;23(6):449-459
159. Arai M, Yokosuka O, Chiba T, et al. Gene expression profiling reveals the mechanism and pathophysiology of mouse liver regeneration. J Biol Chem. 2003;278(32): 29813-29818.
160. Kerr MK, Martin M, Churchill GA. Analysis of variance for gene expression microarray data. J Comput Biol. 2001;7:819-837
161. Wang X, Ghosh S, Guo S. Quantitative quality control in microarray image processing and data acquisition. Nucleic Acids Res. 2001;29:E75.
162. Zhou Y, Gwadry FG, Reinhold WC, et al. Transcriptional regulation of mitotic genes by camptothecin-induced DNA damage: microarray analysis of dose- and time-dependent effects. Cancer Res. 2002;62:1688-1695.
163. .Li Y, Hong X, Hussain M, et al. Gene expression profiling revealed novel molecular targets of docetaxel and estramustine combination treatment in prostate cancer cells, Mol Cancer Ther. 2005;4(3):389-398
164. Matsumura Y, Shimokawa K, Hayashizaki YI, et al. Development of a spot reliability evaluation score for DNA microarrays. Gene. 2005; [Epub ahead of print]
165. Choesmel V, Foucault F, Thiery JP, et al. Design of a real time quantitative PCR assay to assess global mRNA amplification of small size specimens for microarray hybridisation. J Clin Pathol. 2004;57(12): 1278-1287.
166. Brazma A, Hingamp P, Quackenbush J, et al. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet. 2001; 29(4):365-371
167. Hamadeh HK, Bushel PR, Jayadev S, et al. Gene Expression Analysis Reveals Chemical-Specific Profiles. Toxicol. Sci. 2002;67:219-231.
168. Rogers JV, Choi YW, Kiser RC, et al. Microarray analysis of gene expression in murine skin exposed to sulfur mustard. J Biochem Mol Toxicol. 2004; 18(6):289-299.
169. Iida M, Anna CH, Holliday WM, et al. Unique patterns of gene expression changes in liver after treatment of mice for 2 weeks with different known carcinogens and non-carcinogens. Carcinogenesis 2005;26(3):689-699
170. Lee JS, Thorgeirsson SS. Genome-seale profiling of gene expression in hepatocellular carcinoma: Classification, survival prediction, and identification of therapeutic targets. Gastroenterlogy. 2004; 127 (5 suppl 1):s51-59
171. Okabe H, Satoh S, Kato T, et al. Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res. 2001 ;61 (5):2129-2137.
172. Kuramoto T, Morimura K, Yamashita S, et al. Etiology-specific Gene Expression Profiles in Rat Mammary Carcinomas. Cancer Res .2002;62:3592-3597
173.陆巍,王翼飞.基因芯片的信息挖掘.上海大学学报(自然科学版).2003,9(3):272-276
174. Sturn A, Quackenbush J, Trajanoski Z. Genesis: cluster analysis of microarray data. Bioinformatics. 2002; 18(1): 207-208
175. Hunter L, Taylor RC, Leach SM, et al. a gene expression search tool based on a novel Bayesian similarity metric. Bioinformatics. 2001; 17 Suppl 1: S115-22
176. Eisen MB, Brown PO. DNA arrays for analysis of gene expression. Methods Enzymol. 1999; 303:179-205
177. Ross DT, Scherf U, Eisen MB, et al. Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet. 2000 24(3): 227-235
178. Shan L, He M, Yu M, et al. cDNA microarray profiling of rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine and 7,12-dimethylbenz[a]anthracene. Carcinogenesis 2002;23: 1561-1568
179. Nishida K, Mine S, Utsunomiya T, et al. Global Analysis of Altered Gene Expressions during the Process of Esophageal Squamous Cell Carcinogenesis in the Rat: A Study Combined with a Laser Microdissection and a cDNA Microarray. Cancer Res. 2005; 65:401-409
180. Thomas RS, Rank DR, Penn SG,. Identification of toxicologically predictive gene sets using cDNA microarrays. Mol Pharmacol. 2001;60: 1189-1194
181. 182 Shan L, Yu M, Snyderwine EG. Gene expression profiling of chemically induced rat mammary gland cancer. Carcinogenesis 2005 26: 503-509
182. Hess KR, Fuller GN, Rhee CH, et al. Statistical pattern analysis of gene expression profiles for glioblastoma tissues and cell lines. Int J Mol Med. 2001; 8(2): 183-8
183. Mueller MM, Peter W, Mappes M, et al. Tumor progression of skin carcinoma cells in vivo promoted by clonal selection, mutagenesis, and autocrine growth regulation by granulocyte colony-stimulating factor and granulocyte-macrophage. Am-J-Pathol.2001; 159(4): 1567-1579
184. Kayaselcuk F, Zorludemir S, Gumurduhu D, et al.PCNA and Ki-67 in central nervous system tumors: correlation with the histological type and grade. J Neurooncol. 2002;57(2):115-121.
185. Chang PL, Cao M, Hicks P. Osteopontin induction is required for tumor promoter-induced transformation of preneoplastic mouse cells. Carcinogenesis. 2003;24:1749-1758
186. Wen CY, Nakayama T, Wang AP, et al. Expression of pituitary tumor transforming gene in human gastric carcinoma. World J Gastroenterol. 2004; 10(4): 481-483
187. Ravanko K, Jarvinen K, Helin J, et al. Cysteine Cathepsins Are Central Contributors of Invasion by Cultured Adenosylmethionine Decarboxylase-Transformed Rodent Fibroblasts. Cancer Res 2004; 64: 8831-8838
188. Joseph LJ, Chang LC, Stamenkovich D, et al. Complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L. An abundant transcript induced by transformation of fibroblasts. J Clin Invest. 1988;81(5): 1621-1629
189. Atkins KB, Troen BR. Phorbol ester stimulated cathepsin L expression in U937 cells. Cell Growth Differ. 1995; 6(6): 713-718
190. Zwad O, Kubler B, Roth W, et al. Decreased intracellular degradation of insulin-like growth factor binding protein-3 in cathepsin L-deficient fibroblasts. FEBS-Lett. 2002; 510(3): 211-215
191. Powis G, Montfort WR. Properties and biological activities of thioredoxins. Annu Rev Pharmacol Toxicol. 2001;41:261-295.
192. Gallegos A, Gasdaska JR, Taylor CW, et al. Transfection with human thioredoxin increases cell proliferation and a dominant-negative mutant thioredoxin reverses the transformed phenotype of human breast cancer cells. Cancer Res 1996;56: 5765-5770
193. Freemerman AJ, Powis G.A. Redox-Inactive Thioredoxin Reduces Growth and Enhances Apoptosis in WEHI7.2 Cells. Biochem Biophys Res Commun. 2000 Jul 21;274(1):136-141.
194. Kim RH., Peters M, Jang YJ, et al. DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell. 2005;7(3):263-273
195. Meuillet EJ, Mahadevan D, Berggren M, et al. Thioredoxin-1 binds to the C2 domain of PTEN inhibiting PTEN's lipid phosphatase activity and membrane binding: a mechanism for the functional loss of PTEN's tumor suppressor activity. Arch Biochem Biophys. 2004;429(2):123-133
196. Calvo A, Xiao N, Kang J, et al. Alterations in Gene Expression Profiles during Prostate Cancer Progression: Functional Correlations to Tumorigenicity and Down-Regulation of Selenoprotein-P in Mouse and Human Tumors. Cancer Res. 2002;62:5325-5335
197. Gomez DE, Alonso DF, Yoshiji H, et al. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol. 1997; 74(2): 111-122
198. Kleiner DE, Stevenson WG. Matrix metalloproteinases and metastasis. Cancer Chemother Pharmacol. 1999;43 Suppl:S42-51
199. Palamakumbura AH, Sommer P, Trackman PC. Autocrine Growth Factor Regulation of Lysyl Oxidase Expression in Transformed Fibroblasts. J. Biol. Chem. 2003; 278: 30781-30787
200. Ross JS, Kaur P, Sheehan CE, et al. Prognostic significance of matrix
metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression in prostate cancer. Mod Pathol. 2003;16(3):198-205
201. Loewenstein WR, Kanno Y. Intercellular communication and the control of tissue growth: lack of communication between cancer cells. Nature. 1966;209(29): 1248-1249
202. Lampe PD. Analyzing phorbol ester effects on gap junctional communication: a dramatic inhibition of assembly . Cell Biol. 1994; 127:1895-1905
203. Zhang YW, Kaneda M, Morita I. The Gap Junction-independent Tumor-suppressing Effect of Connexin 43. J Biol Chem. 2003;278:44852-44856
204. Gupta N, Wang H, McLeod TL, et al. Inhibition of glioma cell growth and tumorigenic potential by CCN3 (NOV).Mol Pathol. 2001;54(5):293-299
205. Goldberg GS., Bechberger JR, Tajima Y, et al. Connexin43 Suppresses MFG-E8 While Inducing Contact Growth Inhibition of Glioma Cells.Cancer Res. 2000;60:6018-6026
206. Iacovoni JS, Cohen SB, Berg T, et al. v-Jun targets showing an expression pattern that correlates with the transformed cellular phenotype. oncogene. 2004;23(33):5703-5706
207. Haugen BR, Woodmansee WW, McDermott MT. Towards improving the utility of fine-needle aspiration biopsy for the diagnosis of thyroid tumours. Clin-Endocrinol-(Oxf). 2002;56(3): 281-290
208. Yamaoka K, Ohno S, Kawasaki H, et al. Overexpression of a -galactoside binding protein causes transformation of BALB3T3 fibroblast cells. Biochem Biophys Res Commu.l991;172(1):272-279
209. Itzkowitz SH. Galectins: Multipurpose carbohydrate-binding proteins implicated in tumor biology. Gastroenterology. 1997;113(6):2003-2006
210. Sfadia GE, Haklai R, Balan E, et al. Galectin-3 Augments K-Ras Activation and Triggers a Ras Signal That Attenuates ERK but Not Phosphoinositide 3-Kinase Activity. J. Biol. Chem. 2004;279:34922-34930
211. Mirshahi F, Pourtau J, Li H, et al. SDF-1 Activity on Microvascular Endothelial Cells: Consequences on Angiogenesis in in Vitro and in Vivo Models. Thromb Res. 2000;99(6):587-594
212. Broxmeyer HE, Cooper S, Kohli L, et al. Transgenic Expression of Stromal
Cell-Derived Factor-1/CXC Chemokine Ligand 12 Enhances Myeloid Progenitor Cell Survival/Antiapoptosis In Vitro in Response to Growth Factor Withdrawal and Enhances Myelopoiesis In Vivo. Immunol. 2003;170:421-429
213. Lataillade JJ, Clay D, Bourin P, et al. Stromal cell-derived factor 1 regulates primitive hematopoiesis by suppressing apoptosis and by promoting G(0)/G(l) transition in CD34(+) cells: evidence. Blood. 2002;99(4):1117-1129
214. Echtay KS, Roussel D, St-Pierre J, et al. Superoxide activates mitochondrial uncoupling proteins. Nature. 2002;415(6867): 96-99
215. Horimoto M, Fulop P, Derdak Z, et al. Uncoupling protein-2 deficiency promotes oxidant stress and delays liver regeneration in mice. Hepatology. 2004;392(2):386-392
216. Afaq F, Saleem M, Aziz MH, et al. Inhibition of 12-O-tetradecanoylphorbol-13 -acetate-induced tumor promotion markers in CD-I mouse skin by oleandrin. Toxicol Appl Pharmacol. 2004;195(3):361-369
217. Galea Lauri J, Latchman DS, Katz DR. The role of the 90-kDa heat shock protein in cell cycle control and differentiation of the monoblastoid cell line U937. Exp Cell Res.l996;226(2):243-254
218. Akalin A, Elmore LW, Forsythe HL, et al. A Novel Mechanism for Chaperone-mediated Telomerase Regulation during Prostate Cancer Progression. Cancer Res. 2001;61:4791-4796
219. Pratt WB. The role of the hsp90-based chaperone system in signal transduction by nuclear receptors and receptors signaling via MAP kinase. Annu Rev Pharmacol Toxicol. 1997;37:297-326
220. Teng SC, Chen YY, Su YN, et al. Direct Activation of HSP90A Transcription by c-Myc Contributes to c-Myc-induced Transformation. J Biol Chem. 2004;279:14649-14655
221. Sugisawa N, Matsuoka M, Okuno T. Suppression of cadmium-induced JNK/p38 activation and HSP70 family gene expression by LL-Z1640-2 in NIH3T3 cells. Toxicol Appl. Pharmacol. 2004;196(2):206-214
222. Angel JM, DiGiovanni J. Genetics of skin tumor promotion. Prog Exp Tumor Res. 1999;35:143-157
223. Kim E, Muga SJ, Fischer SM.. Identification and Characterization of a Phorbol
Ester-responsive Element in the Murine 8S-Lipoxygenase Gene. J Biol Chem. 2004;279(12):11188-11197
224. Fang MZ, Mar WC, Cho MH. Cadmium-induced alterations of connexin expression in the promotion stage of in vitro two-stage transformation. Toxicology. 2001;161(1-2):117-127
225. Boutwell RK. The function and mechanism of promoters of carcinogenesis. CRC Crit Rev Toxicol. 1974;2(4):419-443
226. Slaga TJ, Scribner JD, Viaje A. Epidermal cell proliferation and promoting ability of phorbol esters. J Natl Cancer Inst. 1976; 57(5):1145-1149
227. Mustacich D, Wagner A, Williams R, et al. Increased skin carcinogenesis in a keratinocyte directed thioredoxin-1 transgenic mouse.Carcinogenesis. 2004; 25(10):1983-1989
228. Rambaratsingh RA, Stone JC. RasGRP1 Represents a Novel Non-protein Kinase C Phorbol Ester Signaling Pathway in Mouse Epidermal Keratinocytes. Biol. Chem. 2003;278(52):52792-52801
229. Schrenk D, Schmitz HJ, Bohnenberger S, et al. Tumor promoters as inhibitors of apoptosis in rat hepatocytes. Toxicol-Lett. 2004; 149(1-3); 43-50
230. Scott ML, Lee JS, Renben L, et al. Biomarkers as intermediate points in chemoprevention trials. J Natl Cancer Inst. 1990;82(7): 555-557
231. Messner DJ, Ao P, Jagdale AB, Abbreviated cell cycle progression induced by the serine/threonine protein phosphatase inhibitor okadaic acid at concentrations that promote neoplastic transformation. Carcinogenesis. 2001;22(8):1163-1172
232. Marks F, Gschwendt M. Gschwendt. Protein kinase C and skin tumor promotion. Mutat Res. 1995 ;333:161-172
233. Viaje A, Slaga TJ, Wigler M, et al. Effects of antiinflammatory agents on mouse skin tumor promotion, epidermal DNA synthesis, phorbol ester-induced cellular proliferation, and production of plasminogen. Cancer Res.l977;37(5):1530-1536
234. Bell GI. Models of carcinogenesis as an escape from mitotic inhibitors. Science. 1976;192(4239): 569-572
235. Solt D, Farber E. New principle for the analysis of chemical Carcinogenesis. Nature.l976;263:701-703
236. Melvin E, Andersen JJ, Mills RL, et al. Negative selection in hepatic tumor promotion in relation to cancer risk assessment. Toxicology,1995;102:223-237
237. Jirtle RL, Meyer SA. Liver tumor promotion: effect of phenobarbital on EGF and protein kinase C signal transduction and transforming growth factor-beta 1 expression. Dig Dis Sci. 1991;36(5):659-668
238. Rumsby PC, Davies MJ, Price RJ, et al. Effect of some peroxisome proliferators on transforming growth factor-beta 1 gene expression and insulin-like growth factor Ⅱ/mannose-6-phosphate. Carcinogenesis. 1994;15(2):419-421
239. Wittinghofer A, Scheffzek K, Ahmadian MR. The interaction of Ras with GTPase-activating proteins. FEBS Lett, 1997;410(1): 63-67.
240. Sears RC ,Nevins JR. Signaling Networks That Link Cell Proliferation and Cell Fate. J Biol Chem. 2002; 277:11617-11620.
241. Moelling K, Schad K, Bosse M, et al. Regulation of Raf-Akt Cross-talk. J Biol Chem, 2002;277:31099-31106.
242. Harris CC. Chemical and physical carcinogenesis: advances and perspectives for the 1990s. Cancer Research.l991;18:5023s-5044s
243. Kaul R, Mukherjee S, Ahmed F, et al. Direct interaction with and activation of p53 by SMARl retards cell-cycle progression at G2/M phase and delays tumor growth in mice. Int J Cancer, 2003;103(5):606-615.
244. Vairapandi M, Balliet AG, Hoffman B, et al. GADD45b and GADD45g are cdc2/cyclinBl kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress. J Cell Physiol, 2002;192(3):327-338.
245. Matsuda S, Rouault J, Magaud J, et al. In search of a function for the TIS21/PC3/BTG1/TOB family. FEBS Lett, 2001;497(2-3):67-72.
246. Bean LJ ,Stark GR. Regulation of the Accumulation and Function of p53 by Phosphorylation of Two Residues within the Domain That Binds to Mdm2. J Biol Chem, 2002; 277:1864-1871.
247. Smith ML, Kontny HU, Bortnick R, et al. The p53-Regulated Cyclin G Gene Promotes Cell Growth: p53 Downstream Effectors Cyclin G and Gadd45 Exert Different Effects on Cisplatin Chemosensitivity. Exp Cell Res. 1997; 230(1):61-68
248. Li P, Nijhawan D, Budihardjo I, et al. Cytochrome c and dATP-dependent formation
of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997; 91(4):479-89
249. Wang QF, Chen JC, Hsieh SJ, et al. Regulation of Bcl-2 family molecules and activation of caspase cascade involved in gypenosides-induced apoptosis in human hepatoma cells. Cancer Lett. 2002;183(2):169-178.
250. Burns TF, Fei P, Scata KA,et al. Silencing of the Novel p53 Target Gene SnklPlk2 Leads to Mitotic Catastrophe in Paclitaxel (Taxol)-Exposed Cells. Mol Cell Biol 2003;23:5556-5571
251. Frey MR, Saxon ML, Zhao X, et al. Protein Kinase C Isozyme-mediated Cell Cycle Arrest Involves Induction of p21~(waf1/cip1) and p27~(kip1) and Hypophosphorylation of the Retinoblastoma Protein in Intestinal Epithelial Cells. J Biol Chem. 1997;272:9424-9435
252. Korkolopoulou P, Angelopoulou MK, Kontopidou F, et al. Prognostic relevance of apoptotic cell death in non-Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression. Histopathology.1998; 33(3):240-247
253. Ashkenazi A, Dixit VM. Death Receptors: Signaling and Modulation. Science. 1998; 281(5381):1305-1308
254. Finkel E. The mitochondrion: is it central to apoptosis? Science. 2001; 292(5517):624-626
255. Yook YH, Kang KH, Maeng O, et al. Nitric oxide induces BNIP3 expression that causes cell death in macrophages. Biochem-Biophys-Res-Commun. 2004; 321(2):298-305
256. Imazu T, Shimizu S, Tagami S, et al. Bcl-2/E1B 19 kDa-interacting protein 3-like protein (Bnip3L) interacts with Bcl-2/Bcl-xL and induces apoptosis by altering mitochondrial membrane permeability. Oncogene. 1999;18(32):4523-4529
257. Chen G, Ray R, Dubik D, et al. The ElB 19K/Bcl-2-binding protein Nip3 is a dimeric mitochondrial protein that activates apoptosis. J-Exp-Med. 1997; 186(12):1975-1983
258. Kang L, Yucheng L, Shelton JM, et al. Cytochrome c Deficiency Causes Embryonic Lethality and Attenuates Stress-Induced Apoptosis. Cell. 2000;101(4):389-399
259. Ni B, Wu X, Du Y, et al. Cloning and expression of a rat brain interleukin-1 beta-converting enzyme (ICE)-related protease (IRP) and its possible role
in apoptosis. J Neurosci. 1997;17(5):1561-1569
260. Lee H, Cha S, Lee M S, et al. Role of antiproliferative B cell translocation gene-1 as an apoptotic sensitizer in activation-induced cell death of brain microglia. J Immunol. 2003;171(11):5802-5811
261. Wu MX. Roles of the stress-induced gene IEX-1 in regulation of cell death and oncogenesis. Apoptosis. 2003;8(l):11-8
262. Todt JC, Hu B, Punturieri A, et al. Activation of Protein Kinase C βⅡ by the Stereo-specific Phosphatidylserine Receptor Is Required for Phagocytosis of Apoptotic Thymocytes by Resident Murine Tissue Macrophages.J. Biol. Chem. 2002 277: 35906-35914.
263. Nicholson KM, Anderson NG The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal. 2002;14(5):381-395.
264. Kennedy SG, Kandel ES, Cross TK, et al. Akt/Protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Mol Cell Biol. 1999;19(8):5800-5810
265. Brunet A, Bonni A, Zigmond MJ, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96(6):857-868.
266. Yang X, Khosravi-Far R, Chang HY, et al. Daxx.a Novel Fas-Binding Protein That Activates JNK and Apoptosis. Cell. 1997;89(7):10667-10676
267. Muromoto R, Yamamoto T, Yumioka T, et al. Daxx enhances Fas-mediated apoptosis in a murine pro-B cell line, BAF3. FEBS Lett. 2003; 540(l-3):223-228
268. Wu S, Loke HN, Rehemtulla A. Ultraviolet radiation-induced apoptosis is mediated by Daxx. Neoplasia. 2002;4:486-492.
269. McGuire S, Bostad E, Smith L, et al. Increased immunoreactivity of glutathione-S-transferase in the retina of Swiss Webster mice following inhalation of JP8+100 aerosol. ArchToxicol. 2002;74:276-280
270. Colangelo D, Mahboobi H, Viarengo A., et al. Protective effect of metallothioneins against oxidative stress evaluated on wild type and MT-null cell lines by means of flow cytometry. Biometals.2004;17(4):265-270
271. Andoh T, Chock PB, Chiueh CC. The Roles of Thioredoxin in Protection against Oxidative Stress-induced Apoptosis in SH-SY5Y Cells. J. Biol. Chem. 2002;277
(12):9655-9660
272. LES Netto, Chae HZ, Kang SW, et al. Removal of Hydrogen Peroxide by Thiol-specific Antioxidant Enzyme (TSA) Is Involved with Its Antioxidant Properties. J Biol Chem. 1996;271(26):15315-15321
273. Bauer I, Wanner GA, Rensing H, et al. Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver. Hepatology. 1998;27(3):829-838
274. Lennon SV, Martin SJ, Cotter TG. Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli. Cell-Prolif. 1991;24(2): 203-214
275. Sato N, Iwata S, Nakamura K. Thiol-mediated redox regulation of apoptosis. Possible roles of cellular thiols other than glutathione in T cell apoptosis. J Immunol.1995;154(7):3194-3203
276. Butterfield LH, Merino A, Golub SH, et al. From cytoprotection to tumor suppression: the multifactorial role of peroxiredoxins. Antioxid Redox Signal. 1999;1(4):3 85-402.
277. Dhar A, Young MR, Colburn NH. The role of AP-1, NF-kappaB and ROS/NOS in skin carcinogenesis: the JB6 model is predictive. Mol Cell Biochem. 2002;234-235(l-2):185-193.
278. Fleury C, Mignotte B, Vayssiere JL. Mitochondrial reactive oxygen species in cell death signaling. Biochimie. 2002;84(2-3):131-141.
279. Facchinetti F, Furegato S, Terrazzino S, et al. H2O2 induces upregulation of Fas and Fas ligand expression in NGF-differentiated PC 12 cells: Modulation by camp. J Neurosci Res. 2002;69(2):178-188
280. Bilodeau JF, Mirault ME. Increased resistance of GPx-1 transgenic mice to tumor promoter-induced loss of glutathione peroxidase activity in skin. Int J Cancer. 1999;80(6):863-867
281. Amoruso MA, Witz G, Goldstein BD. Enhancement of rat and human phagocyte superoxide anion radical production by cadmium in vitro. Toxicol Lett. 1982;10(2-3):133-138
282. Shukla GS, Hussain T, Chandra SV. Possible role of regional superoxide dismutase activity and lipid peroxide levels in cadmium neurotoxicity: in vivo and in vitro studies in growing rats. Life Sci. 1987;41(19):2215-2221
283. Ramirez DC, Riera CM, Gimenez MS. Modulation of arachidonic acid turnover in macrophages by cadmium. Toxicol Lett. 2001;122(1):9-19
284. Leira F, Vieites JM, Vieytes MR, et al. Apoptotic events induced by the phosphatase inhibitor okadaic acid in normal human lung fibroblasts. Toxicol In Vitro. 2001;15(3): 199-208
285. Guo H, Cai CQ, Schroeder RA, et al. Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages. J Immunol. 2001;166(2):1079-1086
286. Su L, Mukherjee AB, Mukherjee BB. Expression of antisense osteopontin RNA inhibits tumor promoter-induced neoplastic transformation of mouse JB6 epidermal cells. Oncogene. 1995;10(11):2163-2169.
287. Behrend EI, Craig AM, Wilson SM, et al. Reduced malignancy of ras-transformed NIH 3T3 cells expressing antisense osteopontin RNA. Cancer Res. 1994;54(3):832-837.
288. Kim HJ, Lee MH, Kim HJ, et al. Okadaic acid stimulates osteopontin expression through de novo induction of AP-1. J Cell Biochem. 2002;87(1):93-102.
289. Craig AM, Smith JH, Denhardt DT. Osteopontin, a transformation-associated cell adhesion phosphoprotein, is induced by 12-O-tetradecanoylphorbol 13-acetate in mouse epidermis. J Biol Chem. 1989;264(16):9682-9689
290. Wai PY, Kuo PC. The role of Osteopontin in tumor metastasis. J Surg Res. 2004; 121(2):228-241
291. Lin YH, Yang-Yen HF. The Osteopontin-CD44 Survival Signal Involves Activation of the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway. J Biol Chem.2001;276:46024-46030
292. Scatena M, Almeida M, Chaisson ML, et al. NF-kB Mediates αvβ3 Integrin-induced Endothelial Cell Survival. J Cell Biol. 1998;141:1083-1093
2. Berenblum I. A re-evaluation of the concept of cocarciongenesis. Prog Exp Tumor Res. 1969;11:21-30.
3. Goerttler K, Loehrke H. Diaplacental carcinogenesis: initiation with the carcinogens dimethylbenzanthracene (DMBA) and urethane during fetal life and postnatal promotion with the phorbol ester TPA in a modified 2-stage Berenblum/Mottram experiment. Virchows Arch A Pathol Anat Histol. 1976; 372(1):29-38.
4. Welsch CW, Nagasawa H. Prolactin and murine mammary tumorigenesis: a review. Cancer Res. 1977; 37(4):951-963.
5. Hirst GL, Balmain A. Forty years of cancer modelling in the mouse. Eur J Cancer. 2004;40(13):1974-1980
6.夏世均,吴中亮主编.《分子毒理学基础》.武汉:湖北科学技术出版社.2001:118-119
7. Turosov VS. Progression of tumors: etiologic, morphologic and molecular-biological aspects. Arkh Patol. 1992;54(7):5-14
8. Hennings H, Lowry DT, Robinson VA, et al. Activity of diverse tumor promoters in a keratinocyte co-culture model of initiated epidermis. Carcinogenesis. 1992; 13(11): 2145-2151
9. Slaga TJ, Budunova Ⅳ, Gimenez-Conti IB, et al. The mouse skin carcinogenesis model. J Investig Dermatol Symp Proc. 1996;1(2):151-156
10. Pitot HC, Dragan YP, Teeguarden J, et al. Quantitation of multistage carcinogenesis in rat liver. Toxicol Pathol. 1996;24(1):119-128
11. Pitot HC, Hikita H, Dragan Y, et al. Review article: the stages of gastrointestinal carcinogenesis—application of rodent models to human disease. Aliment Pharmacol Ther. 2000;14 Suppl 1:153-160
12. Trosko JE. Commentary: is the concept of "tumor promotion" a useful paradigm? Mol Carcinog. 2001 ;30(3): 131-137
13. Pretlow TG, Nagabhushan M, Sy M, et al. Putative preneoplastic foci in the human prostate. J Cell Biochem Suppl. 1994; 19:224-231
14.付立杰主编.《现代毒理学及其应用》.上海:上海科学技术出版社.2001:112-115
15. Owens DM, Wei S, Smart RC. A multihit, multistage model of chemical carcinogenesis. Carcinogenesis. 1999;20(9):1837-1844
16. Pitot HC, Goldsworthy TL, Moran S, et al. A method to quantitate the relative initiating and promoting potencies of hepatocarcinogenic agents in their dose-response relationships to altered hepatic foci. Carcinogenesis. 1987;8(10):1491-1499
17. Hikita H, Vaughan J, Babcock K, et al. Short-term fasting and the reversal of the stage of promotion in rat hepatocarcinogenesis: role of cell replication, apoptosis, and gene expression. Toxicol Sci. 1999;52(2 Suppl):17-23
18. Young MR, Yang HS, Colburn NH. Promising molecular targets for cancer prevention: AP-1, NF-kappa B and Pdcd4. Trends Mol Med. 2003;9(1):36-41
19. Chen ZH, Hurh YJ, Na HK, et al. Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells. Carcinogenesis. 2004;25(10):2005-2013.
20. Schulte-Hermann R, Bursch W, Marian B, et al. Active cell death (apoptosis) and cellular proliferation as indicators of exposure to carcinogens. IARC Sci Publ. 1999;(146):273-85
21.印木泉主编.《遗传毒理学》.北京:科学出版社.2002:268-273
22. Cochet C, Keramidas M, Souvignet C, et al. Phorbol ester-induced alteration of protein kinase C catalytic properties occurs at the membrane level and is not reproduced by physiological stimuli. Biochem Biophys Res Commun. 1986 14;138(3):1283-1290
23.夏世均,吴中亮主编.《分子毒理学基础》.武汉:湖北科学技术出版社.2001:135
24. Pitot HC. Endogenous carcinogenesis: the role of tumor promotion. Proc Soc Exp Biol Med. 1991; 198(2):661-666
25. Williams GM, Iatropoulos MJ, Whysner J. Safety assessment of butylated hydroxyanisole and butylated hydroxytoluene as antioxidant food additives.. Food Chem Toxicol. 1999;37(9-10):1027-1038
26. Lok E, Nera EA, Iverson F, et al. Dietary restriction, cell proliferation and carcinogenesis: a preliminary study. Cancer Lett. 1988;38(3):249-255
27. Weisburger JH. Hazards of fast food. Environ Health Perspect. 2004; 112(6):A336
28. Teeguarden JG, Newton MA, Dragan YP, et al. Genome-wide loss of heterozygosity analysis of chemically induced rat hepatocellular carcinomas reveals elevated frequency of allelic imbalances on chromosomes 1, 6, 8, 11, 15, 17, and 20. Mol Carcinog. 2000;28(1):51-6
29. Ashendel CL, Staller JM, Boutwell RK. Identification of a calcium- and phospholipid- dependent phorbol ester binding activity in the soluble fraction of mouse tissues. Biochem Biophys Res Commun. 1983;111(1):340-345
30. Wheeler DL, Ness KJ, Oberley TD, et al. Inhibition of the development of metastatic squamous cell carcinoma in protein kinase C epsilon transgenic mice by alpha-difluoromethylornithine accompanied by marked hair follicle degeneration and hair loss. Cancer Res. 2003;63(12):3037-3042
31. Lee RG, Rosson D. 12-O-tetradecanoylphorbol-13-acetate induces apoptosis in renal epithelial cells through a growth signal conflict which is prevented by activated ras. Arch Biochem Biophys. 2001;385(2):378-386
32. Patel KV, Schrey MP. Evidence for a role for protein kinase C in the modulation of bombesin-activated cellular signalling in human breast cancer cells. Mol Cell Endocrinol. 1992;85(3):215-225
33. Fujiki H, Suganuma M, Okabe S, et al.A new concept of tumor promotion by tumor necrosis factor-alpha, and cancer preventive agents (-)-epigallocatechin gallate and green tea-a review. Cancer Detect Prev. 2000;24(l):91-99
34. Olden K, Guthrie J. Genomics: implications for toxicology. Mutat Res. 2001; 473(1):3-10
35. Aardema MJ, MacGregor JT. Toxicology and genetic toxicology in the new era of "toxicogenomics": impact of "-omics" technologies. Mutat Res. 2002;499(1): 13-25
36. Schena M, Heller RA, Theriault TP, et al.Microarrays: biotechnology's discovery platform for functional genomics. Trends Biotechnol. 1998;16(7):301-306
37. Afshari CA, Nuwaysir EF, Barrett JC. Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation. Cancer Res. 1999;59(19):4759-4760
38. Nuwaysir EF, Bittner M, Trent J, et al. Microarrays and toxicology: the advent of
toxicogenomics. Mol Carcinog. 1999;24(3):153-159
39. Fa4r S, Dunn RT. Concise review: gene expression applied to toxicology. Toxicol. Sci. 1999;50(1):1-9
40. Morgan KT. Gene Expression Analysis Reveals Chemical-Specific Profiles. Toxicol Sci. 2002;67(2):155-156
41. Jeong JS, Lee SH, Jung KJ, et al. Hepatotoxin N-nitrosomorpholine-induced carcinogenesis in rat liver: ex vivo exploration of preneoplastic and neoplastic hepatocytes. Exp Mol Pathol. 2003;74(1):74-83
42. Pole JC, Gold LI, Orton T, et al. Gene expression changes induced by estrogen and selective estrogen receptor modulators in primary-cultured human endometrial cells: signals that distinguish the human carcinogen tamoxifen. Toxicology. 2005 5;206(1):91-109
43. Harris AJ, Dial SL, Casciano DA. Comparison of basal gene expression profiles and effects of hepatocarcinogens on gene expression in cultured primary human hepatocytes and HepG2 cells. Mutat Res. 2004;549(l-2):79-99
44. Ye J, Shi X. Gene expression profile in response to chromium-induced cell stress in A549 cells. Mol Cell Biochem. 2001;222(1-2):189-197
45. Lee M, Kwon J, Kim SN, et al. cDNA microarray gene expression profiling of hydroxyurea, paclitaxel, and p-anisidine, genotoxic compounds with differing tumorigenicity results. Environ Mol Mutagen. 2003 ;42(2):91-7
46. Schlingemann J, Hess J, Wrobel G, et al. Profile of gene expression induced by the tumour promotor TPA in murine epithelial cells. Int J Cancer. 2003;104(6):699-708
47. Wei SJ, Trempus CS, Cannon RE, et al. Identification of Dssl as a 12-O-tetradecanoylphorbol-13-acetate-responsive gene expressed in keratinocyte progenitor cells, with possible involvement in early skin tumorigenesis. J Biol Chem. 2003;278(3):1758-1768
48. Dhar A, Hu J, Reeves R, et al. Dominant-negative c-Jun (TAM67) target genes: HMGA1 is required for tumor promoter-induced transformation. Oncogene. 2004;23(25):4466-4476
49. Samuel S, Bernstein LR. Adhesion, migration, transcriptional, interferon-inducible, and other signaling molecules newly implicated in cancer susceptibility and resistance
of JB6 cells by cDNA microarray analyses. Mol Carcinog. 2004;39(1):34-60
50. Chan CY, Salabat MR, Ding XZ, et al. Identification and in silico characterization of a novel gene: TPA induced trans-membrane protein. Biochem Biophys Res Commun. 2005 ;329(2):755-764
51. http://ntp-server.niehs.nih.gov/
52. Ashby J, Tennant RW. Definitive relationships among chemical structure, carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat Res. 1991; 257(3): 229-306
53. Dunkel,VC, Rogers C, Swierenga SH, et al. Recommended protocols based on a survey of current practice in genotoxicity testing laboratories: Ⅲ. Cell transformation in C3H/10T1/2 mouse. Mutat. Res. 1991; 246(2): 285-300
54. Matthews EJ, Spalding JW, Tennant RW. Transformation of BALB/c-3T3 cells: Ⅴ. Transformation responses of 168 chemicals compared with mutagenicity in Salmonella and carcinogenicity in rodent bioassays. Environ Health Perspect. 1993;101 Suppl 2:347-482
55. IARC/NCI/EPA Working Group. Cellular and molecular mechanisms of cell transformation and standardization of transformation assays of established cell lines for the prediction of carcinogenic chemicals: overview and recommended protocols. Cancer Res. 1985,45:2395-2399
56. Fang MZ, Kim DY, Lee HW, et al. Improvement of in vitro two-stage transformation assay and determination of the promotional effect of cadmium. Toxicol In Vitro. 2001; 15 (3):225-231
57. Sakai A, Sato M. Improvement of carcinogen identification in BALB/3T3 cell transformation by application of a 2-stage method. Mutat Res. 1989;214(2):285-296.
58.敖琳,曹佳,黄明辉等.佛波酯对BALB/c 3T3细胞转化早期基因表达的影响.中华预防医学杂志.2005:39(2):99-102
59.沈建英,蒋芸,张招弟等.致癌物鉴定方法的现况及展望.中国公共卫生学报.1996;15(6):35-38
60.鄂征主编.《组织培养和分子细胞学技术》.北京出版社.1999.:223-224
61. Todaro GJ, Aaronson SA. Properties of clonal lines of murine sarcoma virus transformed Balb-3T3 cells. Virology. 1969; 38(1): 174-179
62. Aaronson SA, Todaro GJ. Development of 3T3-1ike lines from Balb-c mouse embryo cultures: transformation susceptibility to SV40. J Cell Physiol. 1968; 72(2): 141-148
63. Schechtman LM. BALB/c 3T3 cell transformation: protocols, problems and improvements. IARC Sci Publ. 1985; 67:165-184
64. M Bignami, E Dogliotti, R. Benigni, et al. Split-dose exposure to N-methyl-N'-nitro-N-nitrosoguanidine in BALB/3T3 C1 A31-1-1 cells: Evidence of DNA repair by alkaline elution without changes in cell survival, mutation and transformation rates. Mutat Res. 1985 145(1-2): 81-88.
65. Sakai A, Fujiki H. Promotion of BALB/3T3 cell transformation by the okadaic acid class of tumor promoters, okadaic acid and dinophysistoxin-1. Jpn J Cancer Res. 1991; 82(5): 518-523
66. Katoh F, Fitzgerald DJ, Giroldi L, et al. Okadaic acid and phorbol esters: comparative effects of these tumor promoters on cell transformation, intercellular communication and differentiation in vitro. Jpn J Cancer Res. 1990; 81(6-7): 590-597
67. Tsuchiya T; Umeda M. Relationship between exposure to TPA and appearance of transformed cells in MNNG-initiated transformation of BALB/c 3T3 cells. Int J Cancer. 199; 73(2): 271-276
68. Sakai A. Orthovanadate, an inhibitor of protein tyrosine phosphatases, acts more potently as a promoter than as an initiator in the BALB/3T3 cell transformation. Carcinogenesis. 1997;18(7):1395-1399
69. Landolph JR. Mechanisms of chemically induced multistep neoplastic transformation in C3H 10T 1/2 cells. Carcinog Compr Surv. 1985;10:211-223
70. Reznikoff CA, Bertram JS, Brankow DW, et al. Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of. Cancer Reso 1973; 33(12): 3239-3249
71. Smith GJ, Bell WN, Grisham JW. Clonal analysis of the expression of multiple transformation phenotypes and tumorigenicity by morphologically transformed 10T1/2 cells. Cancer Res. 1993 ; 53(3): 500-508
72. Keshava N. Tumorigenicity of morphologically distinct transformed loci induced by 3-methylcholanthrene in BALB/c-3T3 cells. Mutat Res. 2000; 447(2): 281-286
73.郭仁,张和君,董德详等主编.《分子细胞生物学》.北京医科大学,中国协和医科大 学联合出版社.1995:342-343
74. Wei SJ, Trempus CS, Ali RC, et al. 12-O-Tetradecanoylphorbol-13-acetate and UV Radiation-induced Nucleoside Diphosphate Protein Kinase B Mediates Neoplastic Transformation of Epidermal Cells. J Biol Chem. 2004; 279(7): 5993-6004
75. Tsuchiya T, Umeda M. Improvement in the efficiency of the in vitro transformation assay method using BALB/3T3 A31-1-1 cells. Carcinogenesis. 1995;16(8): 1887-1894
76. Fujimura S, Kogure K, Oboshi S, et al. Production of tumors in glandular stomach of hamsters by N-methyl-N'-nitro-N-nitrosoguanidine. Cancer Res. 1970;30(5): 1444-1448
77. Niknahad H, O'Brien PJ. Cytotoxicity induced by N-methyl-N'-nitro-N-nitrosoguanidine may involve S-nitrosyl glutathione and nitric oxide. Xenobiotica. 1995; 25(1): 91-101
78.冯朝晖,余应年,陈星若等.甲基硝基亚硝基胍诱发的遗传不稳定vero细胞DNA体外复制的保真度.中国药理学与毒理学杂志.1998;(2):144-148
79. Fang MZ, Mar WC, Cho MH. Cell cycle was disturbed in the MNNG-induced initiation stage during in vitro two-stage transformation of Balb/3T3 cells. Toxicology. 2001; 163(2-3): 175-184
80. Edara S, Kanugula S, Pegg AE. Expression of the inactive C145A mutant human O6-alkylguanine-DNA alkyltransferase in E.coli increases cell killing and mutations by N-methyl-N'-nitro-N-nitrosoguanidine. Carcinogenesis. 1999; 20(1): 103-108
81. Tominaga Y, Tsuzuki T, Shiraishi A, et al. Alkylation-induced apoptosis of embryonic stem cells in which the gene for DNA-repair, methyltransferase, had been disrupted by gene targeting. Carcinogenesis. 1997; 18(5): 889-896
82. Jelinsky SA, Samson LD. Global response of Saccharomyces cerevisiae to an alkylating agent. Proc Natl Acad Sci. 1999 96(4): 1486-1491
83. Marczynska B, Khoobyarian N, Chao TS, et al. Phorbol ester promotes growth and transformation of carcinogen-exposed nonhuman primate cells in vitro. Anticancer-Res. 1991; 11(5): 1711-1717
84. Adolf W, Hecker E. On the active principles of the spurge family. Ⅲ. Skin irritant and cocarcinogenic factors from the caper spurge. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1975;84(3):325-344
85. Cochet C, Souvignet C, Keramidas M, et al. Altered catalytic properties of protein kinase C in phorbol ester treated cells. Biochem Biophys Res Commun. 1986;134(3):1031-1037
86. Cabot MC, Welsh CJ, Cao HT, et al. The phosphatidylcholine pathway of diacylglycerol formation stimulated by phorbol diesters occurs via phospholipase D activation. FEBS-Lett. 1988; 233(1): 153-157
87. Huang XP, Da Silva C, Fan XT, et al.Characteristics of arachidonic-acid-mediated brain protein kinase C activation: evidence for concentration-dependent heterogeneity. Biochim Biophys Acta. 1993 17;1175(3):351-356
88. Basu S, Kolesnick R. Stress signals for apoptosis: ceramide and c-Jun kinase. Oncogene. 1998(25): 3277-3285
89. Rice RH, Steinmann KE, Degraffenried LA, et al. Elevation of cell cycle control proteins during spontaneous immortalization of human keratinocytes. Mol-Biol-Cell. 1993;4(2):185-194
90. Hahn MA, Mayne GC. Phorbol ester-induced cell death in PC-12 cells overexpressing Bcl-2 is dependent on the time at which cells are treated. Cell Biol Int. 2004;28(5):345-359
91. Masuda Y,Yoda M,Ohizumi H, et al. Activation of protein kinase C prevents induction of apoptosis by geranylgeraniol in human leukemia HL60 cells. Int J Cancer. 1997;71(4):691-697
92. Suganuma M, Fujiki H, Suguri H, et al. Okadaic acid: an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter. Proc. Natl. Acad. Sci. USA. 1988;85(6):1768-1771
93. Rajesh D, Schell K, Verma AK. Ras Mutation, Irrespective of Cell Type and p53 Status, Determines a Cell's Destiny to Undergo Apoptosis by Okadaic Acid, an Inhibitor of Protein Phosphatase 1 and 2A. Mol Pharmacol 1999 56(3): 515-525
94. Mordan LJ, Dean NM, Honkanen RE, et al. Okadaic acid: a reversible inhibitor of neoplastic transformation of mouse fibroblasts. Cancer Commun. 1990;2(7):237-241
95. Rivedal E, Mikalsen SO, Sanner T. The non-phorbol ester tumor promoter okadaic acid does not promote morphological transformation or inhibit junctional
communication in hamster embryo cells. Biochem Biophys Res Commun. 1990;167(3):1302-1308
96. Gupta RW, Joseph CK, Foster DA. v-Src-induced transformation is inhibited by okadaic acid. Biochem Biophys Res Commun. 1993; 196(1): 320-327
97. Sheu CW, Rodriguez I, Dobras SN, et al. Induction of morphological transformation in BALB/3T3 mouse embryo cells by okadaic acid. Food Chem Toxicol. 1995;33(10):883-885
98. Aonuma S, Ushijima T, Nakayasu M, et al. Mutation induction by okadaic acid, a protein phosphatase inhibitor, in CHL cells, but not in S. typhimurium. Mutat Res. 1991; 250(1-2): 375-381
99. Waalkes MP. Cadmium carcinogenesis. Mutat Res. 2003, 533(l-2):107-120
100. Waalkes MP, Coogan TP, Barter RA. Toxicological principles of metal carcinogenesis with special emphasis on cadmium. Crit Rev Toxicol. 1992;22(3-4): 175-201
101. Achanzar WE., Diwan BA, et al. Cadmium-induced Malignant Transformation of Human Prostate Epithelial Cells. Cancer Res 2001;61:455-458
102. Nakamura K, Yasunaga Y, Ko D, et al. Cadmium-induced neoplastic transformation of human prostate epithelial cells. Int J Oncol. 2002;20(3): 543-547
103. Misra RR, Smith GT, Waalkes MP. Evaluation of the direct genotoxic potential of cadmium in four different rodent cell lines. Toxicology. 1998;126(2):103-114
104. Keshava N, Zhou G, Hubbs AF, et al. Transforming and carcinogenic potential of cadmium chloride in BALB/c-3T3 cells. Mutat Res. 2000; 448(1): 23-28
105. Fang MZ, Mar W, Cho MH. Cadmium affects genes involved in growth regulation during two-stage transformation of Balb/3T3 cells. Toxicology. 2002; 177(2-3): 253-265
106. Beyersmann D, Hechtenberg S. Cadmium, gene regulation, and cellular signalling in mammalian cells. Toxicol Appl Pharmacol. 1997;144(2): 247-261
107. Joseph P, Lei YX, Whong WZ, et al. Molecular cloning and functional analysis of a novel cadmium-responsive proto-oncogene. Cancer Res. 2002;62(3): 703-707
108. Yamada H, Koizumi S. DNA microarray analysis of human gene expression induced by a non-lethal dose of cadmium. Ind Health. 2002;40(2):159-166
109. Fodor SP, Read JL, Pirrung MC, et al. Light-directed, spatially addressable parallel
chemical synthesis. Science. 1991; 251(4995): 767-773
110. Schena M, Shalon D, Davis RW, et al. Quantitative monitoring of gene expression pattems with a complementary DNA microarray. Science. 1995;270(5235):467-470
111.陈永忠,谭晓风.基因芯片技术及其应用前景.中南林学院学报.2003;23(4):100-106
112. Graves DJ. Powerful tools for genetic analysis come of age. Trends Biotechnol. 1999; 17(3): 127-134
113. Lipshutz R, Fodor S , Gingeras T, et al. High desity synthetic oligonucleotide arrays. Nature Gentics supplement. 1999;21:20-24.
114. Halgren RG, Fielden MR, Fong CJ, et al. Assessment of clone identity and sequence fidelity for 1189 IMAGE cDNA clones. Nucleic Acids Res 2001;29:582-588.
115. Huang J, Lih CJ, et al. Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways in Streptomyces coelicolor using DNA microarrays. Genes Development. 2001;15:3183-3192
116. Cheung VG, Morley M, Aguilar F, et al. Making and reading microarrays. Nat Genet. 1999;21(1 Suppl) :15-19
117.丁金凤等主编.《基因分析和生物芯片技术》.武汉:湖北科学技术出版社.2004:199-203
118.马立人,蒋中华主编.《生物芯片》.北京:化学工业出版社.2002:170-180
119. Bassett DE, Eisen MB, et al. Gene expression informatics ? it's all in your mine. Nature Genetics Suppl. 1999;21,:51-55
120. http://dir.niehs.nih.gov/microarray/method.htm
121.伍亚舟,张彦琦,黄明辉等.基因芯片表达数据的标准化策略研究.第三军医大学学报.2004;26(7):594-597
122. http://www.affymetrix.com
123. Shioda T. Application of DNA microarray to toxicological research.. J Environ Pat hol Toxicol Oncol. 2004;23(1): 13-31.
124. Wooster R. Cancer classification with DNA microarrays is less more? Trends Genet. 2000; 16(8):327-329
125. Draghici S, Khatri P, Bhavsar P, et al. Onto-Tools, the toolkit of the modem biologist: Onto-Express, Onto-Compare, Onto-Design and Onto-Translate. Nucleic Acids Res. 2003 ;31(13):3775-3781
126. Smith LL. Key challenges for toxicologists in the 21st century. Trends Pharmacol Sci. 2001 ;22(6): 281-285
127. Simmons PT, Portier CJ. Toxicogenomics: the new frontier in risk analysis. Carcinogenesis. 2002; 23(6): 903-905
128. Lacroix M, Zammatteo N, Remacle J, et al. A low-density DNA microarray for analysis of markers in breast cancer. Int J Biol Markers. 2002; 17 (1): 5-23
129. Stears RL, Martinsky T, Schena M. Trends in microar-ray analysis. Nat Med 2003, 1(9): 140-145.
130. Schlaak JF, Hilkens CM, Costa-Pereira AP, et al. Cell-type and Donor-specific Transcriptional Responses to Interferon-α. J. Biol. Chem. 2002; 277(51): 49428-49437
131. http://www.takara.com
132. http://www.phasetox.com
133. http://www.superarray.com
134. Chuaqui RF, Bonner RF, Best CJM, et al. Post-analysis follow-up and validation of icroarray. Experiments. Nat Genet. 2002; 32 suppl:509-514
135.方志俊,曹佳,敖琳.基因芯片分析显示昆明山海棠有机萃取液经NF-κB及线粒体信号传导途径诱导HL-60细胞凋亡.中草药.2003;34(4):334-338
136.罗瑶,许宏,李瑶等.表达谱基因芯片的可靠性验证分析.遗传学报.2003;30(7):611-618
137. Winzeler EA, Schena M, Davis RW. Fluorescence-based expression monitoring using microarrays. Methods-Enzymol. 1999; 306: 3-18
138. Yue H, Eastman PS, Wang BB, et al. An evaluation of the performance of cDNA microarrays for detecting changes in global mRNA expression. Nucleic Acids Res. 2001; 29(8):E41-1
139.马立人,蒋中华主编.《生物芯片》北京:化学工业出版社,2002:6-7
140. Otto WR. Fluorimetric DNA assay of cell number. Methods Mol Biol. 2005; 289:251-262.
141. Yang YH, Speed T. Design issues for cDNA microarray experiments. Nat Rev Genet. 2002; 3(8):579-588
142. J Quackenbush. Microarray data normalization and transformation. Nature Genetics Suppl .2002; 32:496-501
143.范保星,孙敬芬,刘庆峰等.总RNA和MRNA来源的探针与CDNA芯片杂交的差异研究.生物技术通讯.2004;15(1):20-22
144. Hsiao LL, Jensen RV, Yoshida T, et al. Correcting for signal saturation errors in the analysis of microarray data. Biotechniques. 2002;32(2): 330-2, 334, 336
145. Hill AA, Brown EL, Whitley MZ, et al. Evaluation of normalization procedures for oligonucleotide array data based on spiked cRNA controls. Genome Biol. 2001;2(12): RESEARCH0055
146. Tseng GC, Oh MK, Rohlin L, et al. Issues in cDNA microarray analysis: quality filtering, channel normalization, models of variations and assessment of gene effects. Nucleic Acids Res. 2001; 29(12): 2549-2557
147. Yang YH, Dudoit S, Luu P, et al. Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res. 2002; 30(4): el5
148. Hamalainen HK, Tubman JC, Vikman S, et al. Identification and validation of endogenous reference genes for expression profiling of T helper cell differentiation by quantitative real-time RT-PCR. Anal Biochem. 2001;299(1): 63-70
149. Der SD, Zhou A, Williams BR, et al. Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci USA. 1998; 95(26): 15623-15628
150. Hoerndli FJ, Toigo M, Schild A, et al. Reference genes identified in SH-SY5Y cells using custom-made gene arrays with validation by quantitative polymerase chain reaction. Anal Biochem. 2004;335(1):30-41
151. Warrington JA, Nair A, Mahadevappa M, et al. Comparison of human adult and fetal expression and identification of 535 housekeeping/maintenance genes. Physiol Genomics. 2000; 2(3): 143-147
152. Chen H, Liu J, Merrick BA, et al. Genetic events associated with arsenic-induced malignant transformation: applications of cDNA microarray technology. Mol Carcinog. 2001 ;30(2):79-87.
153. Kepler TB, Crosby L, Morgan KT, et al. Normalization and analysis of DNA microarray data by self-consistency and local regression. Genome Biol. 2002; 3(7): research0037.1-research0037.12.
154.顾永清,杨磊,王国荃等.急性砷染毒的L-02细胞的基因芯片分析.西安交通大学学报,2003;24(6):558-560
155. Rosenzweig BA, Pine PS, Domon OE, et al. Dye bias correction in dual-labeled cDNA microarray gene expression measurements. Environ Health Perspect. 2004; 112(4):480-487.
156. Vissers LE, de Vries BB, Osoegawa K, et al. Array-Based Comparative Genomic Hybridization for the Genomewide Detection of Submicroscopic Chromosomal Abnormalities. Am J Hum Genet. 2003;73(6): 1261-1270
157.158. Li Y, Qiu MY, Wu CQ, et al. Detection of differentially expressed genes in hepatocellular carcinoma using DNA microarray. Yi Chuan Xue Bao. 2000; 27(12): 1042-1048.
158. Ueno Y, Alpini G, Yahagi K, et al. Evaluation of differential gene expression by microarray analysis in small and large cholangiocytes isolated from normal mice. Liver Int. 2003;23(6):449-459
159. Arai M, Yokosuka O, Chiba T, et al. Gene expression profiling reveals the mechanism and pathophysiology of mouse liver regeneration. J Biol Chem. 2003;278(32): 29813-29818.
160. Kerr MK, Martin M, Churchill GA. Analysis of variance for gene expression microarray data. J Comput Biol. 2001;7:819-837
161. Wang X, Ghosh S, Guo S. Quantitative quality control in microarray image processing and data acquisition. Nucleic Acids Res. 2001;29:E75.
162. Zhou Y, Gwadry FG, Reinhold WC, et al. Transcriptional regulation of mitotic genes by camptothecin-induced DNA damage: microarray analysis of dose- and time-dependent effects. Cancer Res. 2002;62:1688-1695.
163. .Li Y, Hong X, Hussain M, et al. Gene expression profiling revealed novel molecular targets of docetaxel and estramustine combination treatment in prostate cancer cells, Mol Cancer Ther. 2005;4(3):389-398
164. Matsumura Y, Shimokawa K, Hayashizaki YI, et al. Development of a spot reliability evaluation score for DNA microarrays. Gene. 2005; [Epub ahead of print]
165. Choesmel V, Foucault F, Thiery JP, et al. Design of a real time quantitative PCR assay to assess global mRNA amplification of small size specimens for microarray hybridisation. J Clin Pathol. 2004;57(12): 1278-1287.
166. Brazma A, Hingamp P, Quackenbush J, et al. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet. 2001; 29(4):365-371
167. Hamadeh HK, Bushel PR, Jayadev S, et al. Gene Expression Analysis Reveals Chemical-Specific Profiles. Toxicol. Sci. 2002;67:219-231.
168. Rogers JV, Choi YW, Kiser RC, et al. Microarray analysis of gene expression in murine skin exposed to sulfur mustard. J Biochem Mol Toxicol. 2004; 18(6):289-299.
169. Iida M, Anna CH, Holliday WM, et al. Unique patterns of gene expression changes in liver after treatment of mice for 2 weeks with different known carcinogens and non-carcinogens. Carcinogenesis 2005;26(3):689-699
170. Lee JS, Thorgeirsson SS. Genome-seale profiling of gene expression in hepatocellular carcinoma: Classification, survival prediction, and identification of therapeutic targets. Gastroenterlogy. 2004; 127 (5 suppl 1):s51-59
171. Okabe H, Satoh S, Kato T, et al. Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res. 2001 ;61 (5):2129-2137.
172. Kuramoto T, Morimura K, Yamashita S, et al. Etiology-specific Gene Expression Profiles in Rat Mammary Carcinomas. Cancer Res .2002;62:3592-3597
173.陆巍,王翼飞.基因芯片的信息挖掘.上海大学学报(自然科学版).2003,9(3):272-276
174. Sturn A, Quackenbush J, Trajanoski Z. Genesis: cluster analysis of microarray data. Bioinformatics. 2002; 18(1): 207-208
175. Hunter L, Taylor RC, Leach SM, et al. a gene expression search tool based on a novel Bayesian similarity metric. Bioinformatics. 2001; 17 Suppl 1: S115-22
176. Eisen MB, Brown PO. DNA arrays for analysis of gene expression. Methods Enzymol. 1999; 303:179-205
177. Ross DT, Scherf U, Eisen MB, et al. Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet. 2000 24(3): 227-235
178. Shan L, He M, Yu M, et al. cDNA microarray profiling of rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine and 7,12-dimethylbenz[a]anthracene. Carcinogenesis 2002;23: 1561-1568
179. Nishida K, Mine S, Utsunomiya T, et al. Global Analysis of Altered Gene Expressions during the Process of Esophageal Squamous Cell Carcinogenesis in the Rat: A Study Combined with a Laser Microdissection and a cDNA Microarray. Cancer Res. 2005; 65:401-409
180. Thomas RS, Rank DR, Penn SG,. Identification of toxicologically predictive gene sets using cDNA microarrays. Mol Pharmacol. 2001;60: 1189-1194
181. 182 Shan L, Yu M, Snyderwine EG. Gene expression profiling of chemically induced rat mammary gland cancer. Carcinogenesis 2005 26: 503-509
182. Hess KR, Fuller GN, Rhee CH, et al. Statistical pattern analysis of gene expression profiles for glioblastoma tissues and cell lines. Int J Mol Med. 2001; 8(2): 183-8
183. Mueller MM, Peter W, Mappes M, et al. Tumor progression of skin carcinoma cells in vivo promoted by clonal selection, mutagenesis, and autocrine growth regulation by granulocyte colony-stimulating factor and granulocyte-macrophage. Am-J-Pathol.2001; 159(4): 1567-1579
184. Kayaselcuk F, Zorludemir S, Gumurduhu D, et al.PCNA and Ki-67 in central nervous system tumors: correlation with the histological type and grade. J Neurooncol. 2002;57(2):115-121.
185. Chang PL, Cao M, Hicks P. Osteopontin induction is required for tumor promoter-induced transformation of preneoplastic mouse cells. Carcinogenesis. 2003;24:1749-1758
186. Wen CY, Nakayama T, Wang AP, et al. Expression of pituitary tumor transforming gene in human gastric carcinoma. World J Gastroenterol. 2004; 10(4): 481-483
187. Ravanko K, Jarvinen K, Helin J, et al. Cysteine Cathepsins Are Central Contributors of Invasion by Cultured Adenosylmethionine Decarboxylase-Transformed Rodent Fibroblasts. Cancer Res 2004; 64: 8831-8838
188. Joseph LJ, Chang LC, Stamenkovich D, et al. Complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L. An abundant transcript induced by transformation of fibroblasts. J Clin Invest. 1988;81(5): 1621-1629
189. Atkins KB, Troen BR. Phorbol ester stimulated cathepsin L expression in U937 cells. Cell Growth Differ. 1995; 6(6): 713-718
190. Zwad O, Kubler B, Roth W, et al. Decreased intracellular degradation of insulin-like growth factor binding protein-3 in cathepsin L-deficient fibroblasts. FEBS-Lett. 2002; 510(3): 211-215
191. Powis G, Montfort WR. Properties and biological activities of thioredoxins. Annu Rev Pharmacol Toxicol. 2001;41:261-295.
192. Gallegos A, Gasdaska JR, Taylor CW, et al. Transfection with human thioredoxin increases cell proliferation and a dominant-negative mutant thioredoxin reverses the transformed phenotype of human breast cancer cells. Cancer Res 1996;56: 5765-5770
193. Freemerman AJ, Powis G.A. Redox-Inactive Thioredoxin Reduces Growth and Enhances Apoptosis in WEHI7.2 Cells. Biochem Biophys Res Commun. 2000 Jul 21;274(1):136-141.
194. Kim RH., Peters M, Jang YJ, et al. DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell. 2005;7(3):263-273
195. Meuillet EJ, Mahadevan D, Berggren M, et al. Thioredoxin-1 binds to the C2 domain of PTEN inhibiting PTEN's lipid phosphatase activity and membrane binding: a mechanism for the functional loss of PTEN's tumor suppressor activity. Arch Biochem Biophys. 2004;429(2):123-133
196. Calvo A, Xiao N, Kang J, et al. Alterations in Gene Expression Profiles during Prostate Cancer Progression: Functional Correlations to Tumorigenicity and Down-Regulation of Selenoprotein-P in Mouse and Human Tumors. Cancer Res. 2002;62:5325-5335
197. Gomez DE, Alonso DF, Yoshiji H, et al. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol. 1997; 74(2): 111-122
198. Kleiner DE, Stevenson WG. Matrix metalloproteinases and metastasis. Cancer Chemother Pharmacol. 1999;43 Suppl:S42-51
199. Palamakumbura AH, Sommer P, Trackman PC. Autocrine Growth Factor Regulation of Lysyl Oxidase Expression in Transformed Fibroblasts. J. Biol. Chem. 2003; 278: 30781-30787
200. Ross JS, Kaur P, Sheehan CE, et al. Prognostic significance of matrix
metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression in prostate cancer. Mod Pathol. 2003;16(3):198-205
201. Loewenstein WR, Kanno Y. Intercellular communication and the control of tissue growth: lack of communication between cancer cells. Nature. 1966;209(29): 1248-1249
202. Lampe PD. Analyzing phorbol ester effects on gap junctional communication: a dramatic inhibition of assembly . Cell Biol. 1994; 127:1895-1905
203. Zhang YW, Kaneda M, Morita I. The Gap Junction-independent Tumor-suppressing Effect of Connexin 43. J Biol Chem. 2003;278:44852-44856
204. Gupta N, Wang H, McLeod TL, et al. Inhibition of glioma cell growth and tumorigenic potential by CCN3 (NOV).Mol Pathol. 2001;54(5):293-299
205. Goldberg GS., Bechberger JR, Tajima Y, et al. Connexin43 Suppresses MFG-E8 While Inducing Contact Growth Inhibition of Glioma Cells.Cancer Res. 2000;60:6018-6026
206. Iacovoni JS, Cohen SB, Berg T, et al. v-Jun targets showing an expression pattern that correlates with the transformed cellular phenotype. oncogene. 2004;23(33):5703-5706
207. Haugen BR, Woodmansee WW, McDermott MT. Towards improving the utility of fine-needle aspiration biopsy for the diagnosis of thyroid tumours. Clin-Endocrinol-(Oxf). 2002;56(3): 281-290
208. Yamaoka K, Ohno S, Kawasaki H, et al. Overexpression of a -galactoside binding protein causes transformation of BALB3T3 fibroblast cells. Biochem Biophys Res Commu.l991;172(1):272-279
209. Itzkowitz SH. Galectins: Multipurpose carbohydrate-binding proteins implicated in tumor biology. Gastroenterology. 1997;113(6):2003-2006
210. Sfadia GE, Haklai R, Balan E, et al. Galectin-3 Augments K-Ras Activation and Triggers a Ras Signal That Attenuates ERK but Not Phosphoinositide 3-Kinase Activity. J. Biol. Chem. 2004;279:34922-34930
211. Mirshahi F, Pourtau J, Li H, et al. SDF-1 Activity on Microvascular Endothelial Cells: Consequences on Angiogenesis in in Vitro and in Vivo Models. Thromb Res. 2000;99(6):587-594
212. Broxmeyer HE, Cooper S, Kohli L, et al. Transgenic Expression of Stromal
Cell-Derived Factor-1/CXC Chemokine Ligand 12 Enhances Myeloid Progenitor Cell Survival/Antiapoptosis In Vitro in Response to Growth Factor Withdrawal and Enhances Myelopoiesis In Vivo. Immunol. 2003;170:421-429
213. Lataillade JJ, Clay D, Bourin P, et al. Stromal cell-derived factor 1 regulates primitive hematopoiesis by suppressing apoptosis and by promoting G(0)/G(l) transition in CD34(+) cells: evidence. Blood. 2002;99(4):1117-1129
214. Echtay KS, Roussel D, St-Pierre J, et al. Superoxide activates mitochondrial uncoupling proteins. Nature. 2002;415(6867): 96-99
215. Horimoto M, Fulop P, Derdak Z, et al. Uncoupling protein-2 deficiency promotes oxidant stress and delays liver regeneration in mice. Hepatology. 2004;392(2):386-392
216. Afaq F, Saleem M, Aziz MH, et al. Inhibition of 12-O-tetradecanoylphorbol-13 -acetate-induced tumor promotion markers in CD-I mouse skin by oleandrin. Toxicol Appl Pharmacol. 2004;195(3):361-369
217. Galea Lauri J, Latchman DS, Katz DR. The role of the 90-kDa heat shock protein in cell cycle control and differentiation of the monoblastoid cell line U937. Exp Cell Res.l996;226(2):243-254
218. Akalin A, Elmore LW, Forsythe HL, et al. A Novel Mechanism for Chaperone-mediated Telomerase Regulation during Prostate Cancer Progression. Cancer Res. 2001;61:4791-4796
219. Pratt WB. The role of the hsp90-based chaperone system in signal transduction by nuclear receptors and receptors signaling via MAP kinase. Annu Rev Pharmacol Toxicol. 1997;37:297-326
220. Teng SC, Chen YY, Su YN, et al. Direct Activation of HSP90A Transcription by c-Myc Contributes to c-Myc-induced Transformation. J Biol Chem. 2004;279:14649-14655
221. Sugisawa N, Matsuoka M, Okuno T. Suppression of cadmium-induced JNK/p38 activation and HSP70 family gene expression by LL-Z1640-2 in NIH3T3 cells. Toxicol Appl. Pharmacol. 2004;196(2):206-214
222. Angel JM, DiGiovanni J. Genetics of skin tumor promotion. Prog Exp Tumor Res. 1999;35:143-157
223. Kim E, Muga SJ, Fischer SM.. Identification and Characterization of a Phorbol
Ester-responsive Element in the Murine 8S-Lipoxygenase Gene. J Biol Chem. 2004;279(12):11188-11197
224. Fang MZ, Mar WC, Cho MH. Cadmium-induced alterations of connexin expression in the promotion stage of in vitro two-stage transformation. Toxicology. 2001;161(1-2):117-127
225. Boutwell RK. The function and mechanism of promoters of carcinogenesis. CRC Crit Rev Toxicol. 1974;2(4):419-443
226. Slaga TJ, Scribner JD, Viaje A. Epidermal cell proliferation and promoting ability of phorbol esters. J Natl Cancer Inst. 1976; 57(5):1145-1149
227. Mustacich D, Wagner A, Williams R, et al. Increased skin carcinogenesis in a keratinocyte directed thioredoxin-1 transgenic mouse.Carcinogenesis. 2004; 25(10):1983-1989
228. Rambaratsingh RA, Stone JC. RasGRP1 Represents a Novel Non-protein Kinase C Phorbol Ester Signaling Pathway in Mouse Epidermal Keratinocytes. Biol. Chem. 2003;278(52):52792-52801
229. Schrenk D, Schmitz HJ, Bohnenberger S, et al. Tumor promoters as inhibitors of apoptosis in rat hepatocytes. Toxicol-Lett. 2004; 149(1-3); 43-50
230. Scott ML, Lee JS, Renben L, et al. Biomarkers as intermediate points in chemoprevention trials. J Natl Cancer Inst. 1990;82(7): 555-557
231. Messner DJ, Ao P, Jagdale AB, Abbreviated cell cycle progression induced by the serine/threonine protein phosphatase inhibitor okadaic acid at concentrations that promote neoplastic transformation. Carcinogenesis. 2001;22(8):1163-1172
232. Marks F, Gschwendt M. Gschwendt. Protein kinase C and skin tumor promotion. Mutat Res. 1995 ;333:161-172
233. Viaje A, Slaga TJ, Wigler M, et al. Effects of antiinflammatory agents on mouse skin tumor promotion, epidermal DNA synthesis, phorbol ester-induced cellular proliferation, and production of plasminogen. Cancer Res.l977;37(5):1530-1536
234. Bell GI. Models of carcinogenesis as an escape from mitotic inhibitors. Science. 1976;192(4239): 569-572
235. Solt D, Farber E. New principle for the analysis of chemical Carcinogenesis. Nature.l976;263:701-703
236. Melvin E, Andersen JJ, Mills RL, et al. Negative selection in hepatic tumor promotion in relation to cancer risk assessment. Toxicology,1995;102:223-237
237. Jirtle RL, Meyer SA. Liver tumor promotion: effect of phenobarbital on EGF and protein kinase C signal transduction and transforming growth factor-beta 1 expression. Dig Dis Sci. 1991;36(5):659-668
238. Rumsby PC, Davies MJ, Price RJ, et al. Effect of some peroxisome proliferators on transforming growth factor-beta 1 gene expression and insulin-like growth factor Ⅱ/mannose-6-phosphate. Carcinogenesis. 1994;15(2):419-421
239. Wittinghofer A, Scheffzek K, Ahmadian MR. The interaction of Ras with GTPase-activating proteins. FEBS Lett, 1997;410(1): 63-67.
240. Sears RC ,Nevins JR. Signaling Networks That Link Cell Proliferation and Cell Fate. J Biol Chem. 2002; 277:11617-11620.
241. Moelling K, Schad K, Bosse M, et al. Regulation of Raf-Akt Cross-talk. J Biol Chem, 2002;277:31099-31106.
242. Harris CC. Chemical and physical carcinogenesis: advances and perspectives for the 1990s. Cancer Research.l991;18:5023s-5044s
243. Kaul R, Mukherjee S, Ahmed F, et al. Direct interaction with and activation of p53 by SMARl retards cell-cycle progression at G2/M phase and delays tumor growth in mice. Int J Cancer, 2003;103(5):606-615.
244. Vairapandi M, Balliet AG, Hoffman B, et al. GADD45b and GADD45g are cdc2/cyclinBl kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress. J Cell Physiol, 2002;192(3):327-338.
245. Matsuda S, Rouault J, Magaud J, et al. In search of a function for the TIS21/PC3/BTG1/TOB family. FEBS Lett, 2001;497(2-3):67-72.
246. Bean LJ ,Stark GR. Regulation of the Accumulation and Function of p53 by Phosphorylation of Two Residues within the Domain That Binds to Mdm2. J Biol Chem, 2002; 277:1864-1871.
247. Smith ML, Kontny HU, Bortnick R, et al. The p53-Regulated Cyclin G Gene Promotes Cell Growth: p53 Downstream Effectors Cyclin G and Gadd45 Exert Different Effects on Cisplatin Chemosensitivity. Exp Cell Res. 1997; 230(1):61-68
248. Li P, Nijhawan D, Budihardjo I, et al. Cytochrome c and dATP-dependent formation
of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997; 91(4):479-89
249. Wang QF, Chen JC, Hsieh SJ, et al. Regulation of Bcl-2 family molecules and activation of caspase cascade involved in gypenosides-induced apoptosis in human hepatoma cells. Cancer Lett. 2002;183(2):169-178.
250. Burns TF, Fei P, Scata KA,et al. Silencing of the Novel p53 Target Gene SnklPlk2 Leads to Mitotic Catastrophe in Paclitaxel (Taxol)-Exposed Cells. Mol Cell Biol 2003;23:5556-5571
251. Frey MR, Saxon ML, Zhao X, et al. Protein Kinase C Isozyme-mediated Cell Cycle Arrest Involves Induction of p21~(waf1/cip1) and p27~(kip1) and Hypophosphorylation of the Retinoblastoma Protein in Intestinal Epithelial Cells. J Biol Chem. 1997;272:9424-9435
252. Korkolopoulou P, Angelopoulou MK, Kontopidou F, et al. Prognostic relevance of apoptotic cell death in non-Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression. Histopathology.1998; 33(3):240-247
253. Ashkenazi A, Dixit VM. Death Receptors: Signaling and Modulation. Science. 1998; 281(5381):1305-1308
254. Finkel E. The mitochondrion: is it central to apoptosis? Science. 2001; 292(5517):624-626
255. Yook YH, Kang KH, Maeng O, et al. Nitric oxide induces BNIP3 expression that causes cell death in macrophages. Biochem-Biophys-Res-Commun. 2004; 321(2):298-305
256. Imazu T, Shimizu S, Tagami S, et al. Bcl-2/E1B 19 kDa-interacting protein 3-like protein (Bnip3L) interacts with Bcl-2/Bcl-xL and induces apoptosis by altering mitochondrial membrane permeability. Oncogene. 1999;18(32):4523-4529
257. Chen G, Ray R, Dubik D, et al. The ElB 19K/Bcl-2-binding protein Nip3 is a dimeric mitochondrial protein that activates apoptosis. J-Exp-Med. 1997; 186(12):1975-1983
258. Kang L, Yucheng L, Shelton JM, et al. Cytochrome c Deficiency Causes Embryonic Lethality and Attenuates Stress-Induced Apoptosis. Cell. 2000;101(4):389-399
259. Ni B, Wu X, Du Y, et al. Cloning and expression of a rat brain interleukin-1 beta-converting enzyme (ICE)-related protease (IRP) and its possible role
in apoptosis. J Neurosci. 1997;17(5):1561-1569
260. Lee H, Cha S, Lee M S, et al. Role of antiproliferative B cell translocation gene-1 as an apoptotic sensitizer in activation-induced cell death of brain microglia. J Immunol. 2003;171(11):5802-5811
261. Wu MX. Roles of the stress-induced gene IEX-1 in regulation of cell death and oncogenesis. Apoptosis. 2003;8(l):11-8
262. Todt JC, Hu B, Punturieri A, et al. Activation of Protein Kinase C βⅡ by the Stereo-specific Phosphatidylserine Receptor Is Required for Phagocytosis of Apoptotic Thymocytes by Resident Murine Tissue Macrophages.J. Biol. Chem. 2002 277: 35906-35914.
263. Nicholson KM, Anderson NG The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal. 2002;14(5):381-395.
264. Kennedy SG, Kandel ES, Cross TK, et al. Akt/Protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Mol Cell Biol. 1999;19(8):5800-5810
265. Brunet A, Bonni A, Zigmond MJ, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96(6):857-868.
266. Yang X, Khosravi-Far R, Chang HY, et al. Daxx.a Novel Fas-Binding Protein That Activates JNK and Apoptosis. Cell. 1997;89(7):10667-10676
267. Muromoto R, Yamamoto T, Yumioka T, et al. Daxx enhances Fas-mediated apoptosis in a murine pro-B cell line, BAF3. FEBS Lett. 2003; 540(l-3):223-228
268. Wu S, Loke HN, Rehemtulla A. Ultraviolet radiation-induced apoptosis is mediated by Daxx. Neoplasia. 2002;4:486-492.
269. McGuire S, Bostad E, Smith L, et al. Increased immunoreactivity of glutathione-S-transferase in the retina of Swiss Webster mice following inhalation of JP8+100 aerosol. ArchToxicol. 2002;74:276-280
270. Colangelo D, Mahboobi H, Viarengo A., et al. Protective effect of metallothioneins against oxidative stress evaluated on wild type and MT-null cell lines by means of flow cytometry. Biometals.2004;17(4):265-270
271. Andoh T, Chock PB, Chiueh CC. The Roles of Thioredoxin in Protection against Oxidative Stress-induced Apoptosis in SH-SY5Y Cells. J. Biol. Chem. 2002;277
(12):9655-9660
272. LES Netto, Chae HZ, Kang SW, et al. Removal of Hydrogen Peroxide by Thiol-specific Antioxidant Enzyme (TSA) Is Involved with Its Antioxidant Properties. J Biol Chem. 1996;271(26):15315-15321
273. Bauer I, Wanner GA, Rensing H, et al. Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver. Hepatology. 1998;27(3):829-838
274. Lennon SV, Martin SJ, Cotter TG. Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli. Cell-Prolif. 1991;24(2): 203-214
275. Sato N, Iwata S, Nakamura K. Thiol-mediated redox regulation of apoptosis. Possible roles of cellular thiols other than glutathione in T cell apoptosis. J Immunol.1995;154(7):3194-3203
276. Butterfield LH, Merino A, Golub SH, et al. From cytoprotection to tumor suppression: the multifactorial role of peroxiredoxins. Antioxid Redox Signal. 1999;1(4):3 85-402.
277. Dhar A, Young MR, Colburn NH. The role of AP-1, NF-kappaB and ROS/NOS in skin carcinogenesis: the JB6 model is predictive. Mol Cell Biochem. 2002;234-235(l-2):185-193.
278. Fleury C, Mignotte B, Vayssiere JL. Mitochondrial reactive oxygen species in cell death signaling. Biochimie. 2002;84(2-3):131-141.
279. Facchinetti F, Furegato S, Terrazzino S, et al. H2O2 induces upregulation of Fas and Fas ligand expression in NGF-differentiated PC 12 cells: Modulation by camp. J Neurosci Res. 2002;69(2):178-188
280. Bilodeau JF, Mirault ME. Increased resistance of GPx-1 transgenic mice to tumor promoter-induced loss of glutathione peroxidase activity in skin. Int J Cancer. 1999;80(6):863-867
281. Amoruso MA, Witz G, Goldstein BD. Enhancement of rat and human phagocyte superoxide anion radical production by cadmium in vitro. Toxicol Lett. 1982;10(2-3):133-138
282. Shukla GS, Hussain T, Chandra SV. Possible role of regional superoxide dismutase activity and lipid peroxide levels in cadmium neurotoxicity: in vivo and in vitro studies in growing rats. Life Sci. 1987;41(19):2215-2221
283. Ramirez DC, Riera CM, Gimenez MS. Modulation of arachidonic acid turnover in macrophages by cadmium. Toxicol Lett. 2001;122(1):9-19
284. Leira F, Vieites JM, Vieytes MR, et al. Apoptotic events induced by the phosphatase inhibitor okadaic acid in normal human lung fibroblasts. Toxicol In Vitro. 2001;15(3): 199-208
285. Guo H, Cai CQ, Schroeder RA, et al. Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages. J Immunol. 2001;166(2):1079-1086
286. Su L, Mukherjee AB, Mukherjee BB. Expression of antisense osteopontin RNA inhibits tumor promoter-induced neoplastic transformation of mouse JB6 epidermal cells. Oncogene. 1995;10(11):2163-2169.
287. Behrend EI, Craig AM, Wilson SM, et al. Reduced malignancy of ras-transformed NIH 3T3 cells expressing antisense osteopontin RNA. Cancer Res. 1994;54(3):832-837.
288. Kim HJ, Lee MH, Kim HJ, et al. Okadaic acid stimulates osteopontin expression through de novo induction of AP-1. J Cell Biochem. 2002;87(1):93-102.
289. Craig AM, Smith JH, Denhardt DT. Osteopontin, a transformation-associated cell adhesion phosphoprotein, is induced by 12-O-tetradecanoylphorbol 13-acetate in mouse epidermis. J Biol Chem. 1989;264(16):9682-9689
290. Wai PY, Kuo PC. The role of Osteopontin in tumor metastasis. J Surg Res. 2004; 121(2):228-241
291. Lin YH, Yang-Yen HF. The Osteopontin-CD44 Survival Signal Involves Activation of the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway. J Biol Chem.2001;276:46024-46030
292. Scatena M, Almeida M, Chaisson ML, et al. NF-kB Mediates αvβ3 Integrin-induced Endothelial Cell Survival. J Cell Biol. 1998;141:1083-1093