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研究生:王家琪
研究生(外文):Chia-Chi Wang
論文名稱:檳榔子水萃取物抑制T細胞活化和引起細胞凋亡之毒性作用
論文名稱(外文):Inhibition of T-cell activation and induction of apoptosis by areca nut extract
指導教授:詹東榮
指導教授(外文):Ton-Rong Jan
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:獸醫學研究所
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:62
中文關鍵詞:T淋巴球細胞激素細胞凋亡檳榔氧化性傷害
外文關鍵詞:T lymphocytecytokineInterferonapoptosisareca nutreactive oxygen species
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嚼食檳榔的習慣普遍流行在東南亞及台灣地區,流行病學研究顯示嚼食檳榔會提高罹患口腔癌的機率,在口腔癌病人中可以觀察到T細胞媒介免疫機能惡化的現象。本實驗主要研究檳榔子水萃取物 (areca nut extract; ANE) 對於離體T細胞功能的影響,並探討其毒性作用的可能機制。ANE (20-60 mg/mL) 抑制小鼠脾臟細胞及EL4細胞分泌IL-2 (T細胞活化的指標),TH1細胞激素IFN-g受到ANE的抑制作用比IL-2更為敏感,於ANE 10 mg/mL以上的濃度即呈現明顯的抑制作用。相反的,ANE對於 TH2細胞激素IL-4的影響則較不明顯。ANE (40-60 mg/mL) 對於脾臟細胞和EL4細胞的代謝活性及增生也呈現濃度相關性的抑制作用。然而給予高達100 μM的檳榔生物鹼 (arecoline 和 arecaidine) 處理,對於細胞存活率和細胞激素的表現並沒有作用,顯示ANE的作用並非由檳榔生物鹼所造成。進一步以RT-PCR分析ANE對於T細胞表現IL-2和 IFN-g mRNA的影響,發現ANE對mRNA的作用不如抑制蛋白質分泌的程度顯著。以annexin V和propidium iodide染色,使用流式細胞儀測定細胞的凋亡反應,發現ANE (20-40 mg/mL) 處理細胞三小時即可觀察到細胞出現凋亡的比率增加,以rhodamine123 染色分析,結果顯示ANE 40 mg/mL處理下,細胞粒腺體膜電位也發生去極化的改變。進一步分析ANE處理細胞的DNA,隨著ANE濃度增加,DNA laddering現象也變得更為明顯。以RNase protection assay 測定EL4細胞 caspase mRNA的表現,發現ANE (20 mg/mL) 處理細胞4小時caspase-2 mRNA 的表現上升。脾臟細胞給予抗氧化劑 N-acetyl-cysteine (NAC, 1-4 mM)、glutathione (GSH, 1-4 mM) 及superoxide dismutase (SOD, 1-400 units) 前處理,對於ANE抑制IL-2和代謝活性的作用有部份的回復效果,對於ANE抑制IFN-g的作用有更顯著的回復效果。
綜合上述,ANE具抑制T細胞活化、增生和誘發凋亡反應的作用,對於TH1細胞激素IFN-g的抑制程度比TH2細胞激素IL-4明顯,上述ANE抑制T細胞的作用可以被抗氧化劑部分回復,顯示ANE的作用可能是經由增加細胞氧化性傷害及誘導T細胞的凋亡反應所造成,而檳榔子中的生物鹼並不是造成ANE抑制T細胞功能的主要成份。
Betel quid chewing is an etiologic factor for oral squamous cell carcinoma (OSCC). Experimental evidence suggests that impaired immune reactivity was associated with the occurrence of OSCC. The objective of the present studies was to investigate the effect of areca nut extract (ANE) on T-cell function and cytokine expression. Pretreatment of splenocytes with ANE suppressed the production of IL-2 and the T-helper 1 (TH1) cytokine IFN-γ induced by PMA/Io. ANE suppression of IL-2 secretion was also demonstrated in EL4 cells. In contrast, the steady state mRNA expression of IL-2 and IFN-γ in splenocytes was not significantly inhibited by ANE. Moreover, ANE treatment produced a marked inhibition on the proliferation of splenocytes and EL4 cells as measured by a MTT assay. A 24-hr exposure of EL4 cells to ANE resulted in a marked reduction in cell viability and growth rate. Treatment of splenocytes and EL4 cells with ANE also increased the percentage of apoptotic cells, as evidenced by annexin V/ propidium iodide flow cytometry and DNA laddering.
For mechanistic studies, the expression of various caspase mRNA in EL4 cells was simultaneously determined by a RNase protection assay. The steady state mRNA expression of caspase-2 was enhanced at 4 hr after ANE treatment. Depolarization of mitochondrial membrane potential in T cells was demonstrated by a decrease in rhodamine123 fluorescence after ANE treatment. The role of reactive oxygen species (ROS) in ANE-mediated effects on cytokine production was further investigated. Pretreatment of splenocytes with anti-oxidants, including N-acetyl-cysteine, superoxide dismutase and glutathione, partially attenuated the effect of ANE on T cell metabolic activity and IL-2 production, whereas ANE-induced suppression of IFN-γ production was almost completely reversed by pretreatment with anti-oxidants.
Taken together, results from the present studies demonstrated that ANE markedly suppressed the activity and cytokine production by T cells, which was associated with the induction of apoptosis in T cells. In addition, the mechanistic studies suggested that the inhibitory effect of ANE on T cell activity and cytokine production was mediated, at least in part, via the induction of ROS in T cells by ANE.
中文摘要 I
Abstract II
簡寫對照表 IV
目錄 V
圖次 VII
表次 VIII
第一章、前言與文獻探討 1
第一節、T淋巴球的功能及其凋亡機制 1
一、T淋巴球及其分泌之細胞激素在免疫系統的功能 1
二、免疫系統對抗腫瘤形成的機制 2
三、T淋巴球凋亡之機制 3
第二節、檳榔成份的致癌性與免疫機能惡化相關性之探討 4
一、檳榔子與檳榔嚼塊的主成分 4
二、檳榔致癌機轉的探討 5
三、嚼食檳榔對免疫系統的影響 7
第二章、實驗材料與方法 10
第一節、藥品資料 10
第二節、實驗方法 12
一、實驗動物與細胞培養模式 12
二、酵素連結免疫吸附試驗(enzyme-linked immunosorbent assay ; ELISA) 12
三、細胞增生與MTT代謝活性的偵測 12
四、RT-PCR 13
五、Multi-probe RNase protection assay (RPA) 13
六、DNA fragmentation assay 14
七、Annexin V/propidium iodide染色分析細胞凋亡 14
八、測定粒腺體膜電位 (mitochondrial membrane protential;△Ψm) 15
九、脾臟細胞CD4+/CD8+ /B220+表面抗原 (surface marker)與annexin V分析 15
十、抗氧化劑對ANE作用之影響 16
十一、數據統計分析 16
第三章、實驗結果 17
第一節、檳榔成分對於T細胞存活、細胞代謝活性、活化及分泌細胞激素的影響 17
一、檳榔子水萃取物(ANE)對於小鼠脾臟細胞及EL4細胞存活率及代謝活性的影響 17
二、ANE對於T細胞分泌細胞激素的影響 17
三、比較ANE、檳榔生物鹼(arecoline及arecaidine)、多酚類檳榔萃取物 (polyphenolic ANE)及黃樟素(safrole)對於脾臟細胞代謝活性及分泌細胞激素的影響 18
第二節、ANE抑制T細胞活化、細胞代謝活性及細胞激素分泌機制的探討 28
一、以RT-PCR測定ANE對於細胞激素mRNA表現的影響 28
二、Annexin V和propidium iodide染色分析ANE誘發T細胞凋亡的發生 28
三、Annexin V和surface marker染色分析ANE誘導不同族群脾臟細胞凋亡的發生 34
四、分析ANE處理後細胞DNA ladder的發生 39
五、以RPA測定ANE處理後細胞表現caspase mRNA的變化 40
六、ANE處理對脾臟細胞粒腺體膜電位的影響 40
七、抗氧化劑對於ANE抑制細胞活化和存活率的保護效果 40
八、抗氧化劑對於ANE抑制分泌細胞激素的保護效果 40
第四章、討論 50
參考文獻 56
圖次
Figure 1. The effect of ANE, arecoline and arecaidine on splenocyte metabolic activity. 19
Figure 2. The effect of ANE and arecoline on the viability and metabolic activity of EL4 cells. 20
Figure 3. The effect of ANE, Arecoline and Arecaidine on splenocyte viability. 21
Figure 4. The effect of ANE on the viability and growth of EL4 cells. 22
Figure 5. The effect of ANE on the production of IL-2, IL-4 and IFN-γ induced by PMA plus ionomycin in splenocytes. 23
Figure 6. The effects of ANE on the production of IL-2 and IL-4 induced by PMA plus ionomycin in EL4 cells. 24
Figure 7. The effect of ANE, Polyphenolic ANE, Arecoline, Arecaidine and Safrole on the production of IL-2 induced by PMA plus ionomycin in splenocytes. 25
Figure 8. The effect of ANE, Polyphenolic ANE, Arecoline, Arecaidine and Safrole on the production of IFN-γinduced by PMA plus ionomycin in splenocytes. 26
Figure 9. The effect of ANE, Polyphenolic ANE, Arecoline, Arecaidine and Safrole on the production of IL-4 induced by PMA plus ionomycin in splenocytes. 27
Figure 10. The effect of ANE on IL-2, IL-4 and IFN-γ mRNA expression induced by PMA plus ionomycin in splenocytes. 29
Figure 11. The effect of ANE on IL-2 and IL-4 mRNA expression induced by PMA plus ionomycin in EL4 cells. 30
Figure 12. Concentration-dependent induction of apoptosis and necrosis by ANE in splenocyte. 31
Figure 13. Concentration-dependent induction of apoptosis and necrosis by ANE in EL4 cells. 32
Figure 14. Time-dependent induction of apoptosis and necrosis by ANE in EL4 cells. 33
Figure 15. Time-dependent induction of apoptosis of splenic CD4+ cells by ANE. 35
Figure 16. Time-dependent induction of apoptosis of splenic CD8+ cells by ANE. 36
Figure 17. Time-dependent induction of apoptosis of splenic B220+ cells by ANE. 37
Figure 18. Time-dependent induction of apoptosis of splenic (A) CD4+, (B) CD8+ and (C) B220+ by ANE. 38
Figure 19. Induction of chromosomal DNA fragmentation in EL4 cells and splenocytes by ANE. 39
Figure 20. The effect of ANE on the steady state mRNA expression of caspases by EL4 cells. 42
Figure 21. The effect of ANE on the steady state mRNA expression of caspases by EL4 cells. 43
Figure 22. Time-dependent induction by ANE of the depolarization of mitochondrial membrane potential in splenocytes. 44
Figure 23. Attenuation of ANE-mediated inhibition of splenocyte metabolic activity by N-acetyl-cysteine (NAC). 45
Figure 24. Attenuation of ANE-mediated inhibition of splenocyte metabolic activity by glutathione (GSH). 46
Figure 25. Attenuation by NAC of ANE-mediated inhibition of IFN-γ production by splenocyte. 47
Figure 26. Attenuation by NAC of ANE-mediated inhibition of IL-2 production by splenocyte. 49

表次
Table 1. Attenuation by NAC, glutathione (GSH) and superoxide dismutase (SOD) of ANE-mediated inhibition of IFN-γ production by splenocytes. 48
al-Sarireh, B., and Eremin, O. (2000). Tumour-associated macrophages (TAMS): disordered function, immune suppression and progressive tumour growth. J R Coll Surg Edinb 45, 1-16.
Apasov, S., Redegeld, F., and Sitkovsky, M. (1993). Cell-mediated cytotoxicity: contact and secreted factors. Curr Opin Immunol 5, 404-410.
Ashby, J., and Tinwell, H. (1994). Use of transgenic mouse lacI/Z mutation assays in genetic toxicology. Mutagenesis 9, 179-181.
Bauer, M. K., Vogt, M., Los, M., Siegel, J., Wesselborg, S., and Schulze-Osthoff, K. (1998). Role of reactive oxygen intermediates in activation-induced CD95 (APO-1/Fas) ligand expression. J Biol Chem 273, 8048-8055.
Boveris, A., and Chance, B. (1973). The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 134, 707-716.
Canniff, J. P., and Harvey, W. (1981). The aetiology of oral submucous fibrosis: the stimulation of collagen synthesis by extracts of areca nut. Int J Oral Surg 10, 163-167.
Chakradeo, P. P., Nair, J., and Bhide, S. V. (1994). Endogenous formation of N-nitrosoproline and other N-nitrosamino acids in tobacco users. Cancer Lett 86, 187-194.
Chang, M. C., Ho, Y. S., Lee, J. J., Kok, S. H., Hahn, L. J., and Jeng, J. H. (2002). Prevention of the areca nut extract-induced unscheduled DNA synthesis of gingival keratinocytes by vitamin C and thiol compounds. Oral Oncol 38, 258-265.
Chang, M. C., Ho, Y. S., Lee, P. H., Chan, C. P., Lee, J. J., Hahn, L. J., Wang, Y. J., and Jeng, J. H. (2001). Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential. Carcinogenesis 22, 1527-1535.
Chang, M. C., Kuo, M. Y., Hahn, L. J., Hsieh, C. C., Lin, S. K., and Jeng, J. H. (1998). Areca nut extract inhibits the growth, attachment, and matrix protein synthesis of cultured human gingival fibroblasts. J Periodontol 69, 1092-1097.
Chang, Y. C., Tai, K. W., Lii, C. K., Chou, L. S., and Chou, M. Y. (1999). Cytopathologic effects of arecoline on human gingival fibroblasts in vitro. Clin Oral Investig 3, 25-29.
Chaudhri, G., Clark, I. A., Hunt, N. H., Cowden, W. B., and Ceredig, R. (1986). Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation. J Immunol 137, 2646-2652.
Chiang, C. P., Wu, H. Y., Liu, B. Y., Wang, J. T., and Kuo, M. Y. (2002). Quantitative analysis of immunocompetent cells in oral submucous fibrosis in Taiwan. Oral Oncol 38, 56-63.
Colombo, M. P., and Trinchieri, G. (2002). Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev 13, 155-168.
D Veries, N., and De Flora, S. (1993). N-acetyl-l-cysteine. J Cell Biochem Suppl 17F, 270-277.
Daimon, H., Sawada, S., Asakura, S., and Sagami, F. (1998). In vivo genotoxicity and DNA adduct levels in the liver of rats treated with safrole. Carcinogenesis 19, 141-146.
Darroudi, F., and Natarajan, A. T. (1993). Metabolic activation of chemicals to mutagenic carcinogens by human hepatoma microsomal extracts in Chinese hamster ovary cells (in vitro). Mutagenesis 8, 11-15.
Davis, S., Weiss, M. J., Wong, J. R., Lampidis, T. J., and Chen, L. B. (1985). Mitochondrial and plasma membrane potentials cause unusual accumulation and retention of rhodamine 123 by human breast adenocarcinoma-derived MCF-7 cells. J Biol Chem 260, 13844-13850.
De Flora, S., Bennicelli, C., Zanacchi, P., Camoirano, A., Morelli, A., and De Flora, A. (1984). In vitro effects of N-acetylcysteine on the mutagenicity of direct-acting compounds and procarcinogens. Carcinogenesis 5, 505-510.
Decker, E. A. (1997). Phenolics: prooxidants or antioxidants? Nutr Rev 55, 396-398.
Dighe, A. S., Richards, E., Old, L. J., and Schreiber, R. D. (1994). Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1, 447-456.
Doherty, P. C. (1997). Cell mediated immunity in virus infections. Biosci Rep 17, 367-387.
Dustin, M. L. (2003). Coordination of T cell activation and migration through formation of the immunological synapse. Ann N Y Acad Sci 987, 51-59.
Ehrlich, R. (1997). Modulation of antigen processing and presentation by persistent virus infections and in tumors. Hum Immunol 54, 104-116.
Flagg, E. W., Coates, R. J., Jones, D. P., Byers, T. E., Greenberg, R. S., Gridley, G., McLaughlin, J. K., Blot, W. J., Haber, M., Preston-Martin, S., and et al. (1994). Dietary glutathione intake and the risk of oral and pharyngeal cancer. Am J Epidemiol 139, 453-465.
Goldstone, S. D., Milligan, A. D., and Hunt, N. H. (1996). Oxidative signalling and gene expression during lymphocyte activation. Biochim Biophys Acta 1314, 175-182.
Granstein, R. D., Deak, M. R., Jacques, S. L., Margolis, R. J., Flotte, T. J., Whitaker, D., Long, F. H., and Amento, E. P. (1989). The systemic administration of gamma interferon inhibits collagen synthesis and acute inflammation in a murine skin wounding model. J Invest Dermatol 93, 18-27.
Green, D. R. (2003). Overview: apoptotic signaling pathways in the immune system. Immunol Rev 193, 5-9.
Grisham, M. B. (2004). Reactive oxygen species in immune responses. Free Radic Biol Med 36, 1479-1480.
Haque, M. F., Harris, M., Meghji, S., and Barrett, A. W. (1998). Immunolocalization of cytokines and growth factors in oral submucous fibrosis. Cytokine 10, 713-719.
Haque, M. F., Harris, M., Meghji, S., and Speight, P. M. (1997). An immunohistochemical study of oral submucous fibrosis. J Oral Pathol Med 26, 75-82.
Haque, M. F., Meghji, S., Khitab, U., and Harris, M. (2000). Oral submucous fibrosis patients have altered levels of cytokine production. J Oral Pathol Med 29, 123-128.
Haque, M. F., Meghji, S., Nazir, R., and Harris, M. (2001). Interferon gamma (IFN-gamma) may reverse oral submucous fibrosis. J Oral Pathol Med 30, 12-21.
Harding, C. V. (1993). Cellular and molecular aspects of antigen processing and the function of class II MHC molecules. Am J Respir Cell Mol Biol 8, 461-467.
Hildeman, D. A., Zhu, Y., Mitchell, T. C., Bouillet, P., Strasser, A., Kappler, J., and Marrack, P. (2002). Activated T cell death in vivo mediated by proapoptotic bcl-2 family member bim. Immunity 16, 759-767.
Hiroaki Ikeda, L. J. o., Robert D. Schreiber (2002). The roles of IFN-r in protection against tumor develpment and cancer immunoediting. In Cytokine and growth factor reviews, pp. 95-109.
Hung, S. L., Chen, Y. L., Wan, H. C., Liu, T. Y., Chen, Y. T., and Ling, L. J. (2000). Effects of areca nut extracts on the functions of human neutrophils in vitro. J Periodontal Res 35, 186-193.
IARC (1985a). Betel-quid and areca-nut chewing. IARC Monogr Eval Carcinog Risk Chem Hum 37, 141-291.
IARC (1985b). Tobacco habits other than smoking; betel-quid and areca-nut chewing; and some related nitrosamines. IARC Working Group. Lyon, 23-30 October 1984. IARC Monogr Eval Carcinog Risk Chem Hum 37, 1-268.
Ikeda, H., Old, L. J., and Schreiber, R. D. (2002). The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev 13, 95-109.
Imberti, R., Nieminen, A. L., Herman, B., and Lemasters, J. J. (1993). Mitochondrial and glycolytic dysfunction in lethal injury to hepatocytes by t-butylhydroperoxide: protection by fructose, cyclosporin A and trifluoperazine. J Pharmacol Exp Ther 265, 392-400.
Jain, A., Martensson, J., Stole, E., Auld, P. A., and Meister, A. (1991). Glutathione deficiency leads to mitochondrial damage in brain. Proc Natl Acad Sci U S A 88, 1913-1917.
Jan, T. R., Farraj, A. K., Harkema, J. R., and Kaminski, N. E. (2003). Attenuation of the ovalbumin-induced allergic airway response by cannabinoid treatment in A/J mice. Toxicol Appl Pharmacol 188, 24-35.
Jeng, J. H., Hahn, L. J., Lin, B. R., Hsieh, C. C., Chan, C. P., and Chang, M. C. (1999). Effects of areca nut, inflorescence piper betle extracts and arecoline on cytotoxicity, total and unscheduled DNA synthesis in cultured gingival keratinocytes. J Oral Pathol Med 28, 64-71.
Jeng, J. H., Kuo, M. L., Hahn, L. J., and Kuo, M. Y. (1994). Genotoxic and non-genotoxic effects of betel quid ingredients on oral mucosal fibroblasts in vitro. J Dent Res 73, 1043-1049.
Jeng, J. H., Lan, W. H., Hahn, L. J., Hsieh, C. C., and Kuo, M. Y. (1996). Inhibition of the migration, attachment, spreading, growth and collagen synthesis of human gingival fibroblasts by arecoline, a major areca alkaloid, in vitro. J Oral Pathol Med 25, 371-375.
Jeng, J. H., Wang, Y. J., Chang, W. H., Wu, H. L., Li, C. H., Uang, B. J., Kang, J. J., Lee, J. J., Hahn, L. J., Lin, B. R., and Chang, M. C. (2004). Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells. Cell Mol Life Sci 61, 83-96.
Jeng, J. H., Wang, Y. J., Chiang, B. L., Lee, P. H., Chan, C. P., Ho, Y. S., Wang, T. M., Lee, J. J., Hahn, L. J., and Chang, M. C. (2003). Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin E2, interleukin-6 and TNF-alpha production of oral epithelial cells by areca nut extract and arecoline. Carcinogenesis 24, 1301-1315.
Jiang, X., and Wang, X. (2004). Cytochrome C-mediated apoptosis. Annu Rev Biochem 73, 87-106.
Johnson, N. W., Warnakulasuriy, S., and Tavassoli, M. (1996). Hereditary and environmental risk factors; clinical and laboratory risk matters for head and neck, especially oral, cancer and precancer. Eur J Cancer Prev 5, 5-17.
Kagan, V. E., and Tyurina, Y. Y. (1998). Recycling and redox cycling of phenolic antioxidants. Ann N Y Acad Sci 854, 425-434.
Kaur, S. J., Grover, I. S., and Kumar, S. (2000). Modulatory effects of a tannin fraction isolated from Terminalia arjuna on the genotoxicity of mutagens in Salmonella typhimurium. Food Chem Toxicol 38, 1113-1119.
Ko YC, C. T., Chang SJ, Hsieh SF. (1992). Prevalence of betel quid chewing habit in Taiwan and related sociodemographic factors. J Oral Pathol Med. 1992 Jul;21(6):261-4.
Kuo, M. Y., Jeng, J. H., Chiang, C. P., and Hahn, L. J. (1994). Mutations of Ki-ras oncogene codon 12 in betel quid chewing-related human oral squamous cell carcinoma in Taiwan. J Oral Pathol Med 23, 70-74.
Kuttan, R., Donnelly, P. V., and Di Ferrante, N. (1981). Collagen treated with (+)-catechin becomes resistant to the action of mammalian collagenase. Experientia 37, 221-223.
Leprat, P., Ratinaud, M. H., Maftah, A., Petit, J. M., and Julien, R. (1990). Use of nonyl acridine orange and rhodamine 123 to follow biosynthesis and functional assembly of mitochondrial membrane during L1210 cell cycle. Exp Cell Res 186, 130-137.
Li, Y. Q., Kobayashi, M., Yuan, L., Wang, J., Matsushita, K., Hamada, J. I., Kimura, K., Yagita, H., Okumura, K., and Hosokawa, M. (1998). Protein kinase C mediates the signal for interferon-gamma mRNA expression in cytotoxic T cells after their adhesion to laminin. Immunology 93, 455-461.
Lin, C. F., Chen, C. L., Chang, W. T., Jan, M. S., Hsu, L. J., Wu, R. H., Tang, M. J., Chang, W. C., and Lin, Y. S. (2004). Sequential caspase-2 and caspase-8 activation upstream of mitochondria during ceramideand etoposide-induced apoptosis. J Biol Chem 279, 40755-40761.
Liu, T. Y., Chen, C. L., and Chi, C. W. (1996). Oxidative damage to DNA induced by areca nut extract. Mutat Res 367, 25-31.
Ma, R. H., Tsai, C. C., and Shieh, T. Y. (1995). Increased lysyl oxidase activity in fibroblasts cultured from oral submucous fibrosis associated with betel nut chewing in Taiwan. J Oral Pathol Med 24, 407-412.
Maezawa, Y., Nakajima, H., Kumano, K., Kubo, S., Karasuyama, H., and Iwamoto, I. (2003). Role of IgE in Th2 cell-mediated allergic airway inflammation. Int Arch Allergy Immunol 131 Suppl 1, 2-6.
Meghji, S., Scutt, A., Harvey, W., and Canniff, J. P. (1987). An in-vitro comparison of human fibroblasts from normal and oral submucous fibrosis tissue. Arch Oral Biol 32, 213-215.
Murti, P. R., Bhonsle, R. B., Gupta, P. C., Daftary, D. K., Pindborg, J. J., and Mehta, F. S. (1995). Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing. J Oral Pathol Med 24, 145-152.
Murti PR, B. R., Gupta PC, Daftary DK, Pindborg JJ, Mehta FS. (1995). Etiology of oral submucous fibrosis with special reference to the role of areca
nut chewing. J Oral Pathol Med. 1995 Apr;24(4):145-52.
Nair, U., Bartsch, H., and Nair, J. (2004). Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms. Mutagenesis 19, 251-262.
Nair, U. J., Floyd, R. A., Nair, J., Bussachini, V., Friesen, M., and Bartsch, H. (1987). Formation of reactive oxygen species and of 8-hydroxydeoxyguanosine in DNA in vitro with betel quid ingredients. Chem Biol Interact 63, 157-169.
Nair, U. J., Friesen, M., Richard, I., MacLennan, R., Thomas, S., and Bartsch, H. (1990). Effect of lime composition on the formation of reactive oxygen species from areca nut extract in vitro. Carcinogenesis 11, 2145-2148.
Nair, U. J., Nair, J., Friesen, M. D., Bartsch, H., and Ohshima, H. (1995). Ortho- and meta-tyrosine formation from phenylalanine in human saliva as a marker of hydroxyl radical generation during betel quid chewing. Carcinogenesis 16, 1195-1198.
Nair, U. J., Obe, G., Friesen, M., Goldberg, M. T., and Bartsch, H. (1992). Role of lime in the generation of reactive oxygen species from betel-quid ingredients. Environ Health Perspect 98, 203-205.
Nelson, B. S., and Heischober, B. (1999). Betel nut: a common drug used by naturalized citizens from India, Far East Asia, and the South Pacific Islands. Ann Emerg Med 34, 238-243.
Nickoloff, B. J., and Turka, L. A. (1993). Keratinocytes: key immunocytes of the integument. Am J Pathol 143, 325-331.
Parkin, D. M., Pisani, P., and Ferlay, J. (1993). Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 54, 594-606.
Prokopczyk, B., Rivenson, A., Bertinato, P., Brunnemann, K. D., and Hoffmann, D. (1987). 3-(Methylnitrosamino)propionitrile: occurrence in saliva of betel quid chewers, carcinogenicity, and DNA methylation in F344 rats. Cancer Res 47, 467-471.
Ranadive, K. J., Gothoskar, S. V., Rao, A. R., Tezabwalla, B. U., and Ambaye, R. Y. (1976). Experimental studies on betel nut and tobacco carcinogenicity. Int J Cancer 17, 469-476.
Randerath, K., Gupta, K. P., and van Golen, K. L. (1993). Altered fidelity of a nucleic acid modifying enzyme, T4 polynucleotide kinase, by safrole-induced DNA damage. Carcinogenesis 14, 1523-1529.
Rathmell, J. C., and Thompson, C. B. (2002). Pathways of apoptosis in lymphocyte development, homeostasis, and disease. Cell 109 Suppl, S97-107.
Robertson, J. D., Enoksson, M., Suomela, M., Zhivotovsky, B., and Orrenius, S. (2002). Caspase-2 acts upstream of mitochondria to promote cytochrome c release during etoposide-induced apoptosis. J Biol Chem 277, 29803-29809.
Romagnani, S. (1999). Th1/Th2 cells. Inflamm Bowel Dis 5, 285-294.
Rudin, C. M., Van Dongen, J., and Thompson, C. B. (1996). Apoptotic signaling in lymphocytes. Curr Opin Hematol 3, 35-40.
Sankaranarayanan, R., Mathew, B., Varghese, C., Sudhakaran, P. R., Menon, V., Jayadeep, A., Nair, M. K., Mathews, C., Mahalingam, T. R., Balaram, P., and Nair, P. P. (1997). Chemoprevention of oral leukoplakia with vitamin A and beta carotene: an assessment. Oral Oncol 33, 231-236.
Santana, M. A., and Rosenstein, Y. (2003). What it takes to become an effector T cell: the process, the cells involved, and the mechanisms. J Cell Physiol 195, 392-401.
Saunders, N. A., and Jetten, A. M. (1994). Control of growth regulatory and differentiation-specific genes in human epidermal keratinocytes by interferon gamma. Antagonism by retinoic acid and transforming growth factor beta 1. J Biol Chem 269, 2016-2022.
Schwartz, R. H. (1992). Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 71, 1065-1068.
Shankaran, V., Ikeda, H., Bruce, A. T., White, J. M., Swanson, P. E., Old, L. J., and Schreiber, R. D. (2001). IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410, 1107-1111.
Shirname, L. P., Menon, M. M., Nair, J., and Bhide, S. V. (1983). Correlation of mutagenicity and tumorigenicity of betel quid and its ingredients. Nutr Cancer 5, 87-91.
Sirsat, S. M., and Khanolkar, V. R. (1962). The effect of arecoline on the palatal and buccal mucosa of the Wistar rat. An optical and electron microscope study. Indian J Med Sci 16, 198-202.
Smyth, M. J., Godfrey, D. I., and Trapani, J. A. (2001). A fresh look at tumor immunosurveillance and immunotherapy. Nat Immunol 2, 293-299.
Street, S. E., Cretney, E., and Smyth, M. J. (2001). Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97, 192-197.
Sundqvist, K., and Grafstrom, R. C. (1992). Effects of areca nut on growth, differentiation and formation of DNA damage in cultured human buccal epithelial cells. Int J Cancer 52, 305-310.
Sundqvist, K., Liu, Y., Nair, J., Bartsch, H., Arvidson, K., and Grafstrom, R. C. (1989). Cytotoxic and genotoxic effects of areca nut-related compounds in cultured human buccal epithelial cells. Cancer Res 49, 5294-5298.
Thomas, S. J., and MacLennan, R. (1992). Slaked lime and betel nut cancer in Papua New Guinea. Lancet 340, 577-578.
Trivedy, C., Meghji, S., Warnakulasuriya, K. A., Johnson, N. W., and Harris, M. (2001). Copper stimulates human oral fibroblasts in vitro: a role in the pathogenesis of oral submucous fibrosis. J Oral Pathol Med 30, 465-470.
Troy, C. M., and Shelanski, M. L. (2003). Caspase-2 redux. Cell Death Differ 10, 101-107.
Verastegui, E., Morales, R., Barrera, J. L., Mueller, A., Guzman, B., Meneses, A., and Alfaro, G. (2002). Immunological approach in the evaluation of regional lymph nodes of patients with squamous cell carcinoma of the head and neck. Clin Immunol 102, 37-47.
Wang, C. K., and Peng, C. H. (1996). The mutagenicities of alkaloids and N-nitrosoguvacoline from betel quid. Mutat Res 360, 165-171.
Wong, D. Y., Hsiao, Y. L., Poon, C. K., Kwan, P. C., Chao, S. Y., Chou, S. T., and Yang, C. S. (1994). Glutathione concentration in oral cancer tissues. Cancer Lett 81, 111-116.
Xu, X., Fu, X. Y., Plate, J., and Chong, A. S. (1998). IFN-gamma induces cell growth inhibition by Fas-mediated apoptosis: requirement of STAT1 protein for up-regulation of Fas and FasL expression. Cancer Res 58, 2832-2837.
Young, H. A., and Hardy, K. J. (1995). Role of interferon-gamma in immune cell regulation. J Leukoc Biol 58, 373-381.
Young, M. R., Wright, M. A., Lozano, Y., Matthews, J. P., Benefield, J., and Prechel, M. M. (1996). Mechanisms of immune suppression in patients with head and neck cancer: influence on the immune infiltrate of the cancer. Int J Cancer 67, 333-338.
Zhivotovsky, B. (2004). Apoptosis, necrosis and between. Cell Cycle 3, 64-66.
Zou, H., Li, Y., Liu, X., and Wang, X. (1999). An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 274, 11549-11556.
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