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研究生:林依玲
研究生(外文):Yii-Ling Lin
論文名稱:亞砷酸鈉前處理對於人類癌細胞株絲裂黴素C感受性之影響
論文名稱(外文):Modulation of Human Cancer Cell Lines to Mitomycin C Susceptibility by Sodium Arsenite Pretreatment
指導教授:李德章李德章引用關係
指導教授(外文):Te-Chang Lee
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2003
畢業學年度:91
語文別:中文
論文頁數:78
中文關鍵詞:亞砷酸鈉絲裂黴素C
外文關鍵詞:sodium arsenitemitomycin C
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  • 被引用被引用:1
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  • 下載下載:13
  • 收藏至我的研究室書目清單書目收藏:0
砷化物自古以來就廣泛被應用於醫學上,近幾年臨床研究發現無機砷對於耐受的(refractory)或復發的(relapsed)急性前骨髓細胞性白血病(acute promyelocytic leukemia, APL)病患的治療非常有效,但對於實體性腫瘤(solid tumor)的效用仍在臨床試驗階段。砷化物用於治療癌症的機轉包括有促進細胞分化、凋亡(apoptosis)及抑制細胞生長以及血管新生(angiogenesis)等。本論文的目的為尋找受亞砷酸鈉影響的標的基因(target gene),企圖在癌症治療上開發更具療效的應用模式。
由本實驗室cDNA微陣列技術分析結果發現2 μM亞砷酸鈉處理人類肺腺癌CL3細胞24小時導致NAD(P)H quinone oxidoreductase 1 (NQO1)、glutathione peroxidase 2 (GPX2)以及heme oxygenase-1 (HO-1) mRNA表現量增加。本論文則以北方墨點法分析確認其mRNA表現量的增加,並以西方墨點法及酵素測定活性分析印證NQO1的蛋白質及酵素活性也都有增加的現象。NQO1是一個奎諾類還原脢,對於奎諾類化合物的代謝扮演著相當重要的角色,因此進一步探討亞砷酸鈉前處理誘引NQO1酵素活性增加是否改變細胞對奎諾類化合物的感受性。結果發現亞砷酸鈉前處理會使得CL3細胞對奎諾類化合物mitomycin C的感受性增加,加入NQO1抑制劑dicumarol則可使亞砷酸鈉促進細胞對mitomycin C的感受性消失,顯示亞砷酸鈉與mitomycin C合併使用藉由誘引NQO1可增加毒殺細胞的效果,亞砷酸鈉前處理對其他奎諾類藥物如:adriamycin、menadione以及mitoxantrone的細胞毒殺能力則無明顯的改變。
亞砷酸鈉對NQO1的誘引在不同癌細胞株有不同的反應,如亞砷酸鈉無法誘導在人類大細胞型肺癌H460細胞NQO1活性上升,但可誘導人類大細胞型肺癌H1299細胞以及人類尿道上皮MC-SV-HUC-1致癌性細胞中NQO1酵素活性上升,同時也增加細胞對mitomycin C的感受性。因此對於可被亞砷酸鈉誘導NQO1之癌細胞,合併使用亞砷酸鈉與mitomycin C之療效值得進一步的動物及臨床試驗。

Arsenic has been extensively used in medicine for a long time. In recent years, therapy with arsenic trioxide offers the opportunity for a complete remission and improved survival in patients with refractory or relapsed acute promyelocytic leukemia (APL). However, therapy with arsenic in sold tumors is still on clinical trials. Mechanisms of arsenic action in cancer therapy include induction of cytodifferentiation, apoptosis, and inhibition of cell proliferation and angiogenesis, etc. The objective of this study attempts to find suitable target genes altered by arsenic and to establish an effective cancer therapy protocol for other cancers.
In a preliminary cDNA microarray study in our laboratory, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase 2 (GPX2) and heme oxygenase-1 (HO-1) were induced in human lung adenocarcinoma CL3 cells treated with 2 μM sodium arsenite for 24h. In the present study, the enhanced mRNA expression of these genes was further confirmed by Western blot assay. Among these genes, increased protein level and enzyme activity of NQO1 were confirmed by western blot technique and enzymatic activity assay. Since NQO1 is a quinone reductase that physiologically plays an important role on quinone drug metabolism, the influences of the quinone compounds’ cytotoxicity by arsenite via enhanced NQO1 expression were examined by colony forming assay in CL3 cells. Among quinone drugs tested, sodium arsenite pretreatment resulted in increased susceptibility of mitomycin C to CL3 cells but had no obvious influence on susceptibility of adriamycin, menadione and mitoxantrone. Furthermore, dicumarol, a specific inhibitor of NQO1, was shown to abrogate the increased susceptibility of CL3 cells to mitomycin C by arsenite. These results demonstrated the involvement of NQO1 in increased susceptibility to mitomycin C by arsenite pretreatment.
To investigate the therapeutic potential of arsenite pretreatment in different cell types, the present results demonstrated that arsenite pretreatment resulted in increased NQO1 activity and susceptibility to mitomycin C in human lung large cell carcinoma H1299 cells and human uroepithelium MC-SV-HUC-1 cells. In contrast, arsenite pretreatment showed neither enhancement of NQO1 expression nor susceptibility to mitomycin C in human lung large cell carcinoma H460 cells. These results revealed that the therapeutic effectiveness of combination of arsenite and mitomycin C in cancer cells that NQO1 expression is enhanced by arsenite pretreatment warrants further animal and clinical trials in the future.

目錄
目錄 ………………………………………………………………………… I
圖目錄 …………………………………………………………………… V
中文摘要 ………………………………………………………………… VI
英文摘要 ………………………………………………………………… VIII
第一章 緒論 ……………………………………………………………… 1
第一節前言 ………………………………………………………… 1
壹、砷化物簡介 ……………………………………………… 1
貳、砷化物在醫療上的應用 ……………………………… 2
1. 使用砷化物治療的歷史 …………………………… 2
2. 砷化物與癌症治療 ………………………………… 2
參、Mitomycin C簡介 ……………………………………… 4
1. Bioreductive藥物-mitomycin C …………………… 4
2. Mitomycin C應用在癌症治療 …………………… 5
肆、NAD(P)H:quinone oxidoreductase 1 (NQO1) ……… 5
1. NQO1的簡介 ……………………………………… 5
2. NQO1基因調控 …………………………………… 6
3. NQO1的基因多型性 (polymorphism) …………… 6
4. NQO1扮演著解毒的角色 ………………………… 7
5. 受NQO1活化的藥物 ……………………………… 9
6. NQO1與mitomcyin C之關係 …………………… 11
第二節 研究動機及實驗目的 ……………………………………… 12
第二章 材料與方法 ……………………………………………………… 13
1. 化學藥品 ……………………………………………………… 13
2. 細胞培養 ……………………………………………………… 13
3. Total RNA 抽取 ………………………………………………… 14
4. 反轉錄-聚合鏈反應 (RT-PCR) ……………………………… 15
5. Digoxigenin標定之cDNA探針製備 ………………………… 16
6. 北方墨點法分析法 (Northern blot analysis) ………………… 17
7. 蛋白質定量 ……………………………………………………… 18
8. 西方墨點法分析法 (Western blot analysis) ………………… 19
9. NQO1酵素活性測定 …………………………………………… 19
10. 細胞毒性 (cytotoxicity) 分析 ……………………………… 20
(1) 細胞群落形成分析法 (Colony Forming assay) ……… 20
(2) Sulforhodamine B分析法 (SRB assay) ……………… 21
11. 統計方法 ……………………………………………………… 22
第三章 結果 ……………………………………………………………… 23
第一節 亞砷酸鈉處理對CL3細胞基因表現的影響 …………… 23
壹、亞砷酸鈉促進CL3細胞內GPX2之表現 …………… 23
貳、亞砷酸鈉誘導CL3細胞內HO-1之表現 …………… 23
參、亞砷酸鈉促進CL3細胞內NQO1之表現 …………… 24
第二節 亞砷酸鈉前處理對於奎諾類化合物細胞毒性之影響 … 24
壹、亞砷酸鈉前處理對於CL3細胞mitomycin C感受性之影響……………………………………………………… 25
貳、亞砷酸鈉前處理對於CL3細胞adriamycin感受性之影響………………………………………………………… 25
參、亞砷酸鈉前處理對於CL3細胞menadione感受性之影響………………………………………………………… 26
肆、亞砷酸鈉前處理對於CL3細胞mitoxantrone感受性之影響……………………………………………………… 26
伍、NQO1抑制劑使得細胞對於亞砷酸鈉前處理所促進的mitomycin C感受性消失……………………………… 26
第三節 亞砷酸鈉前處理對於其他人類癌細胞株mitomycin C感受性之影響………………………………………………… 27
壹、亞砷酸鈉對CL3、H460、H1299以及MC-SV-HUC-1癌細胞株之毒性分析…………………………………… 28
貳、亞砷酸鈉前處理H460細胞對mitomycin C感受性的影響………………………………………………………… 28
參、亞砷酸鈉前處理對H1299細胞mitomycin C感受性的影響……………………………………………………… 28
肆、亞砷酸鈉前處理對MC-SV-HUC-1細胞mitomycin C感受性的影響……………………………………………… 29
第四章 討論 ……………………………………………………………… 31
第一節 亞砷酸鈉處理CL3細胞造成的基因表現變化 ……… 31
壹、亞砷酸鈉促進CL3細胞內GPX2之表現 …………… 31
貳、亞砷酸鈉促進CL3細胞內HO-1之表現 …………… 32
參、亞砷酸鈉促進CL3細胞內NQO1之表現 …………… 34
第二節 亞砷酸鈉前處理對於奎諾類化合物細胞毒性之影響 … 34
壹、亞砷酸鈉前處理對於CL3細胞mitomycin C感受性之影響……………………………………………………… 34
貳、亞砷酸鈉前處理對於CL3細胞adriamycin感受性之影響………………………………………………………… 35
參、亞砷酸鈉前處理對於CL3細胞menadione感受性之影響………………………………………………………… 36
肆、亞砷酸鈉前處理對於CL3細胞mitoxantrone感受性之影響……………………………………………………… 36
第三節 亞砷酸鈉前處理對於其他人類癌細胞株mitomycin C感受性之影響………………………………………………… 37
第五章 總結與展望 ……………………………………………………… 39
參考文獻 …………………………………………………………………… 40
附錄一 奎諾類化合物還原反應示意圖 ……………………………… 79
附錄二 Mitomycin C、adriamycin、menadione以及mitoxantrone之化學結構。………………………………………………… 80
附錄三 本實驗室未發表cDNA微陣列分析結果 …………………… 81

Applegate, L. A., Luscher, P., and Tyrrell, R. M. (1991). Induction of heme oxygenase: a general response to oxidant stress in cultured mammalian cells. Cancer Res. 51, 974-978.
Aronson, S. M. (1994). Arsenic and old myths. R. I. Med. 77, 233-234.
Balla, G., Jacob, H. S., Balla, J., Rosenberg, M., Nath, K., Apple, F., Eaton, J. W., and Vercellotti,G.M. (1992). Ferritin: a cytoprotective antioxidant strategem of endothelium. J. Biol. Chem. 267, 18148-18153.
Beall, H. D. and Winski, S. I. (2000). Mechanisms of action of quinone-containing alkylating agents. I: NQO1-directed drug development. Front Biosci. 5, D639-D648.
Begleiter, A., Leith, M. K., and Curphey, T. J. (1996). Induction of DT-diaphorase by 1,2-dithiole-3-thione and increase of antitumour activity of bioreductive agents. Br. J. Cancer Suppl 27, S9-14.
Behne, D. and Kyriakopoulos, A. (2001). Mammalian selenium-containing proteins. Annu. Rev. Nutr. 21, 453-473.
Belcourt, M. F., Hodnick, W. F., Rockwell, S., and Sartorelli, A. C. (1996). Bioactivation of mitomycin antibiotics by aerobic and hypoxic Chinese hamster ovary cells overexpressing DT-diaphorase. Biochem. Pharmacol. 51, 1669-1678.
Belinsky, M. and Jaiswal, A. K. (1993). NAD(P)H:quinone oxidoreductase1 (DT-diaphorase) expression in normal and tumor tissues. Cancer Metastasis Rev. 12, 103-117.
Benson, A. M., Hunkeler, M. J., and Talalay, P. (1980). Increase of NAD(P)H:quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity. Proc. Natl. Acad. Sci. U.S.A 77, 5216-5220.
Benson, A. M. (1993). Conversion of 4-nitroquinoline 1-oxide (4NQO) to 4-hydroxyaminoquinoline 1-oxide by a dicumarol-resistant hepatic 4NQO nitroreductase in rats and mice. Biochem. Pharmacol. 46, 1217-1221.
Beyer, R. E., Segura-Aguilar, J., Di Bernardo, S., Cavazzoni, M., Fato, R., Fiorentini, D., Galli, M. C., Setti, M., Landi, L., and Lenaz (1996). The role of DT-diaphorase in the maintenance of the reduced antioxidant form of coenzyme Q in membrane systems. Proc. Natl. Acad. Sci. U.S.A 93, 2528-2532.
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254.
Bradner, W. T. (2001). Mitomycin C: a clinical update. Cancer Treat. Rev. 27, 35-50.
Burnette, W. N. (1981). "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal. Biochem. 112, 195-203.
Chiou, T. J., Chou, Y. T., and Tzeng, W. F. (1998). Menadione-induced cell degeneration is related to lipid peroxidation in human cancer cells. Proc. Natl. Sci. Counc. Repub. China B 22, 13-21.
Chiou, T. J. and Tzeng, W. F. (2000). The roles of glutathione and antioxidant enzymes in menadione-induced oxidative stress. Toxicology 154, 75-84.
Choi, A. M. and Alam, J. (1996). Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am. J. Respir. Cell Mol. Biol. 15, 9-19.
Chomczynski, P. (1993). A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 15, 532-537.
Chomczynski, P. and Sacchi, N. (1987). Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162, 156-159.
Chu, F. F., Doroshow, J. H., and Esworthy, R. S. (1993). Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. J. Biol. Chem. 268, 2571-2576.
Clairmont, A., Sies, H., Ramachandran, S., Lear, J. T., Smith, A. G., Bowers, B., Jones, P. W., Fryer, A. A., and Strange, R. C. (1999). Association of NAD(P)H:quinone oxidoreductase (NQO1) null with numbers of basal cell carcinomas: use of a multivariate model to rank the relative importance of this polymorphism and those at other relevant loci. Carcinogenesis 20, 1235-1240.
Coceani, F. (1993). Carbon monoxide and dilation of blood vessels. Science 260, 739.
Curt, G. A., Kelley, J. A., Kufta, C. V., Smith, B. H., Kornblith, P. L., Young, R. C., and Collins, J. M. (1983). Phase II and pharmacokinetic study of aziridinylbenzoquinone [2,5-diaziridinyl-3,6-bis(carboethoxyamino)-1,4-benzoquinone, diaziquone, NSC 182986] in high-grade gliomas. Cancer Res. 43, 6102-6105.
De Beer, E. L., Bottone, A. E., and Voest, E. E. (2001). Doxorubicin and mechanical performance of cardiac trabeculae after acute and chronic treatment: a review. Eur. J. Pharmacol. 415, 1-11.
De Long, M. J., Prochaska, H. J., and Talalay, P. (1986). Induction of NAD(P)H:quinone reductase in murine hepatoma cells by phenolic antioxidants, azo dyes, and other chemoprotectors: a model system for the study of anticarcinogens. Proc. Natl. Acad. Sci. U.S.A 83, 787-791.
Delnomdedieu, M., Basti, M.M., Otvos, J. D., and Thomas, D. J. (1993). Transfer of arsenite from glutathione to dithiols: a model of interaction. Chem. Res. Toxicol. 6, 598-602.
Doherty, G. P., Leith, M. K., Wang, X., Curphey, T. J., and Begleiter, A. (1998). Induction of DT-diaphorase by 1,2-dithiole-3-thiones in human tumour and normal cells and effect on anti-tumour activity of bioreductive agents. Br. J. Cancer 77, 1241-1252.
Durante, W., Kroll, M. H., Christodoulides, N., Peyton, K. J., and Schafer, A. I. (1997). Nitric oxide induces heme oxygenase-1 gene expression and carbon monoxide production in vascular smooth muscle cells. Circ. Res. 80, 557-564.
Duthie, S. J. and Grant, M. H. (1989). The role of reductive and oxidative metabolism in the toxicity of mitoxantrone, adriamycin and menadione in human liver derived Hep G2 hepatoma cells. Br. J. Cancer 60, 566-571.
Engler-Blum, G., Meier, M., Frank, J., and Muller, G. A. (1993). Reduction of background problems in nonradioactive northern and Southern blot analyses enables higher sensitivity than 32P-based hybridizations. Anal. Biochem. 210, 235-244.
Ernster, L. (1967). DT Diaphorase. In Methods in enzymology ; v.10, pp. 309-317.
Fitzsimmons, S. A., Workman, P., Grever, M., Paull, K., Camalier, R., and Lewis, A. D. (1996). Reductase enzyme expression across the National Cancer Institute Tumor cell line panel: correlation with sensitivity to mitomycin C and EO9. J. Natl. Cancer Inst. 88, 259-269.
Forkner, C. E. and Scott, T. F. M. (1931). Arsenic as a therapeutic agent in chronic myelogenous leukemia. JAMA 97, 3-5.
Gaedigk, A., Tyndale, R. F., Jurima-Romet, M., Sellers, E. M., Grant, D. M., and Leeder, J. S. (1998). NAD(P)H:quinone oxidoreductase: polymorphisms and allele frequencies in Caucasian, Chinese and Canadian Native Indian and Inuit populations. Pharmacogenetics 8, 305-313.
Ganousis, L. G., Goon, D., Zyglewska, T., Wu, K. K., and Ross, D. (1992). Cell-specific metabolism in mouse bone marrow stroma: studies of activation and detoxification of benzene metabolites. Mol. Pharmacol. 42, 1118-1125.
Gewirtz, D. A. (1999). A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem. Pharmacol. 57, 727-741.
Gustafson, D. L., Beall, H. D., Bolton, E. M., Ross, D., and Waldren, C. A. (1996). Expression of human NAD(P)H: quinone oxidoreductase (DT-diaphorase) in Chinese hamster ovary cells: effect on the toxicity of antitumor quinones. Mol. Pharmacol. 50, 728.
Gustafson, D. L. and Pritsos, C. A. (1992). Bioactivation of mitomycin C by xanthine dehydrogenase from EMT6 mouse mammary carcinoma tumors. J. Natl. Cancer Inst. 84, 1180-1185.
Haller, J. S. (1975). Therapeutic mule: the use of arsenic in the nineteenth century materia medica. Pharm. Hist 17, 87-100.
Hayashi, T., Kanetoshi, A., Nakamura, M., Tamura, M., and Shirahama, H. (1992). Reduction of alpha-tocopherolquinone to alpha-tocopherolhydroquinone in rat hepatocytes. Biochem. Pharmacol. 44, 489-493.
Hodnick, W. F. and Sartorelli, A. C. (1993). Reductive activation of mitomycin C by NADH:cytochrome b5 reductase. Cancer Res. 53, 4907-4912.
Joseph, P. and Jaiswal, A. K. (1994). NAD(P)H:quinone oxidoreductase1 (DT diaphorase) specifically prevents the formation of benzo[a]pyrene quinone-DNA adducts generated by cytochrome P4501A1 and P450 reductase. Proc. Natl. Acad. Sci. U.S.A 91, 8413-8417.
Joseph, P., Jaiswal, A. K., Stobbe, C. C., and Chapman, J. D. (1994). The role of specific reductases in the intracellular activation and binding of 2-nitroimidazoles. Int. J. Radiat. Oncol. Biol. Phys. 29, 351-355.
Kelsey, K. T., Ross, D., Traver, R. D., Christiani, D. C., Zuo, Z. F., Spitz, M. R., Wang, M., Xu, X., Lee, B. K., and Schwartz (1997). Ethnic variation in the prevalence of a common NAD(P)H quinone oxidoreductase polymorphism and its implications for anti-cancer chemotherapy. Br. J. Cancer 76, 852-854.
Keyes, S. R., Fracasso, P. M., Heimbrook, D. C., Rockwell, S., Sligar, S. G., and Sartorelli, A. C. (1984). Role of NADPH:cytochrome c reductase and DT-diaphorase in the biotransformation of mitomycin C1. Cancer Res. 44, 5638-5643.
Keyse, S. M. and Tyrrell, R. M. (1989). Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc. Natl. Acad. Sci. U. S. A 86, 99-103.
Kitchin, K. T. and Ahmad, S. (2003). Oxidative stress as a possible mode of action for arsenic carcinogenesis. Toxicol. Lett. 137, 3-13.
Klassen, C. D. (1996). Heavy metals and heavy-metal antagonists. In Goodman & Gilman's The Pharmacological Basis of Therapeutics., J.G.Hardman, A.G.Gilman, and L.E.Limbird, eds. (New York: McGraw-Hill), pp. 1649-1672.
Knox, R. J., Boland, M. P., Friedlos, F., Coles, B., Southan, C., and Roberts, J. J. (1988). The nitroreductase enzyme in walker cells that activates 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) to 5-(aziridin-1-YL)-4-hydroxylamino-2-nitrobenzamide is a form of NAD(P)H dehydrogenase (quinone) (EC 1.6.99.2). Biochem. Pharmacol. 37, 4671-4677.
Kohar, I., Baca, M., Suarna, C., Stocker, R., and Southwell-Keely, P. T. (1995). Is [alpha]-tocopherol a reservoir for [alpha]-tocopheryl hydroquinone? Free Radic. Biol. Med. 19, 197-207.
Kwong, Y. L. and Todd, D. (1997). Delicious poison: arsenic trioxide for the treatment of leukemia. Blood 89, 3487-3488.
Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.
Lee, P. J., Alam, J., Wiegand,G.W., and Choi,A.M. (1996). Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia. Proc. Natl. Acad. Sci. U. S. A 93, 10393-10398.
Lee, T. C. and Ho, I. C. (1994). Expression of heme oxygenase in arsenic-resistant human lung adenocarcinoma cells. Cancer Res. 54, 1660-1664.
Leffler, C. W., Nasjletti, A., Yu, C., Johnson, R. A., Fedinec, A. L., and Walker, N. (1999). Carbon monoxide and cerebral microvascular tone in newborn pigs. Am. J. Physiol 276, H1641-H1646.
Lind, C., Cadenas, E., Hochstein, P., and Ernster, L. (1990). DT-diaphorase: purification, properties, and function. Methods Enzymol. 186, 287-301.
Loadman, P. M., Phillips, R. M., Lim, L. E., and Bibby, M. C. (2000). Pharmacological properties of a new aziridinylbenzoquinone, RH1 (2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone), in mice. Biochem. Pharmacol. 59, 831-837.
Lovell, M. A. and Farmer, J. G. (1985). Arsenic speciation in urine from humans intoxicated by inorganic arsenic compounds. Hum. Toxicol. 4, 203-214.
Lown, J. W., Begleiter, A., Johnson, D., and Morgan, A. R. (1976). Studies related to antitumor antibiotics. Part V. Reactions of mitomycin C with DNA examined by ethidium fluorescence assay. Can. J. Biochem. 54, 110-119.
Maines, M. D. (1997). The heme oxygenase system: a regulator of second messenger gases. Annu. Rev. Pharmacol. Toxicol. 37, 517-554.
Malkinson, A. M., Siegel, D., Forrest, G. L., Gazdar, A. F., Oie, H. K., Chan, D. C., Bunn, P. A., Mabry, M., Dykes, D. J., and Harrison, S. D. (1992). Elevated DT-diaphorase activity and messenger RNA content in human non-small cell lung carcinoma: relationship to the response of lung tumor xenografts to mitomycin Cl. Cancer Res. 52, 4752.
Menzel, D. B., Rasmussen, R. E., Lee, E., Meacher, D. M., Said, B., Hamadeh, H., Vargas, M., Greene, H., and Roth, R. N. (1998). Human lymphocyte heme oxygenase 1 as a response biomarker to inorganic arsenic. Biochem. Biophys. Res. Commun. 250, 653-656.
Mikami, K., Naito, M., Tomida, A., Yamada, M., Sirakusa, T., and Tsuruo, T. (1996). DT-diaphorase as a critical determinant of sensitivity to mitomycin C in human colon and gastric carcinoma cell lines. Cancer Res 56, 2823-2826.
Miller, W. H., Jr., Schipper, H. M., Lee, J. S., Singer, J., and Waxman, S. (2002). Mechanisms of action of arsenic trioxide. Cancer Res. 62, 3893-3903.
Munday, R., Smith, B. L., and Munday, C. M. (1999). Effect of inducers of DT-diaphorase on the toxicity of 2-methyl- and 2-hydroxy-1,4-naphthoquinone to rats. Chemico-Biological Interactions 123, 219-237.
Neuzil, J. and Stocker, R. (1994). Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J. Biol. Chem. 269, 16712-16719.
Nutter, L. M., Ngo, E. O., Fisher, G. R., and Gutierrez, P. L. (1992). DNA strand scission and free radical production in menadione-treated cells. Correlation with cytotoxicity and role of NADPH quinone acceptor oxidoreductase. J. Biol. Chem. 267, 2474-2479.
Olson, R. D. and Mushlin, P. S. (1990). Doxorubicin cardiotoxicity: analysis of prevailing hypotheses. FASEB J. 4, 3076-3086.
Oradell, N. J. (1975). Physicians' Desk Reference (Medical Economics Company), pp. 642-643.
Pan, S. S., Andrews, P. A., Glover, C. J., and Bachur, N. R. (1984). Reductive activation of mitomycin C and mitomycin C metabolites catalyzed by NADPH-cytochrome P-450 reductase and xanthine oxidase. J. Biol. Chem. 259, 959-966.
Patterson, A. V., Saunders, M. P., Chinje, E. C., Patterson, L. H., and Stratford, I. J. (1998). Enzymology of tirapazamine metabolism: a review. Anti-Cancer Drug Design 13, 541-573.
Phillips, R. M., Burger, A. M., Loadman, P. M., Jarrett, C. M., Swaine, D. J., and Fiebig, H. H. (2000). Predicting tumor responses to mitomycin C on the basis of DT-diaphorase activity or drug metabolism by tumor homogenates: implications for enzyme-directed bioreductive drug development. Cancer Res. 60, 6384-6390.
Powis, G., Gasdaska, P. Y., Gallegos, A., Sherrill, K., and Goodman, D. (1995). Over-expression of DT-diaphorase in transfected NIH 3T3 cells does not lead to increased anticancer quinone drug sensitivity: a questionable role for the enzyme as a target for bioreductively activated anticancer drugs. Anticancer Res. 15, 1141-1145.
Primiano, T., Kensler, T. W., Kuppusamy, P., Zweier, J. L., and Sutter, T. R. (1996). Induction of hepatic heme oxygenase-1 and ferritin in rats by cancer chemopreventive dithiolethiones. Carcinogenesis 17, 2291-2296.
Pritsos, C. A. and Sartorelli, A. C. (1986). Generation of reactive oxygen radicals through bioactivation of mitomycin antibiotics. Cancer Res. 46, 3528-3532.
Radjendirane, V., Joseph, P., Lee, Y. H., Kimura, S., Klein-Szanto, A. J., Gonzalez, F. J., and Jaiswal, A. K. (1998). Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione toxicity. J. Biol. Chem. 273, 7382-7389.
Robertson, N., Haigh, A., Adams, G. E., and Stratford, I. J. (1994). Factors affecting sensitivity to EO9 in rodent and human tumour cells in vitro: DT-diaphorase activity and hypoxia. Eur. J. Cancer 30A, 1013-1019.
Ross, D. (1997). Quinone reductases : Biotransformation. Comprehensive Toxicology, F.P.Guengerich, ed. (New York: Pergamon), pp. 179-198.
Ross, D., Siegel, D., Beall, H., Prakash, A. S., Mulcahy, R. T., and Gibson, N. W. (1993). DT-diaphorase in activation and detoxification of quinones. Bioreductive activation of mitomycin C. Cancer Metastasis Rev. 12, 83-101.
Ross, D., Siegel, D., Gibson, N. W., Pacheco, D., Thomas, D. J., Reasor, M., and Wierda, D. (1990). Activation and deactivation of quinones catalyzed by DT-diaphorase. Evidence for bioreductive activation of diaziquone (AZQ) in human tumor cells and detoxification of benzene metabolites in bone marrow stroma. Free Radic. Res. Commun. 8, 373-381.
Ross, D., Kepa, J. K., Winski, S. L., Beall, H. D., Anwar, A., and Siegel, D. (2000). NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chemico-Biological Interactions 129, 77-97.
Rust, D. M. and Soignet, S. L. (2001). Risk/benefit profile of arsenic trioxide. Oncologist. 6 Suppl 2, 29-32.
Sachs, D., Flemming, R. A., and Miller, M. S. (2000). Biochemical modulation of mitymycin C by induction of NAD(P)H:quinone oxidoreductase 1. Proc. Am. Assoc. Cancer Res. 41, 4-5.
Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989). Molecular cloning: A laboratory manual. (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press).
Schelonka, L. P., Siegel, D., Wilson, M. W., Meininger, A., and Ross, D. (2000). Immunohistochemical localization of NQO1 in epithelial dysplasia and neoplasia and in donor eyes. Invest Ophthalmol. Vis. Sci. 41, 1617-1622.
Schipper, H. M. (2000). Heme oxygenase-1: role in brain aging and neurodegeneration. Exp. Gerontol. 35, 821-830.
Schmitz, G. G., Walter, T., Seibl, R., and Kessler, C. (1991). Nonradioactive labeling of oligonucleotides in vitro with the hapten digoxigenin by tailing with terminal transferase. Anal. Biochem. 192, 222-231.
Schulz, W. A., Krummeck, A., Rosinger, I., Eickelmann, P., Neuhaus, C., Ebert, T., Schmitz-Drager, B. J., and Sies, H. (1997). Increased frequency of a null-allele for NAD(P)H: quinone oxidoreductase in patients with urological malignancies. Pharmacogenetics 7, 235-239.
Siegel, D., Anwar, A., Winski, S. L., Kepa, J. K., Zolman, K. L., and Ross, D. (2001). Rapid polyubiquitination and proteasomal degradation of a mutant form of NAD(P)H:quinone oxidoreductase 1. Mol. Pharmacol. 59, 263-268.
Siegel, D., Beall, H., Senekowitsch, C., Kasai, M., Arai, H., Gibson, N. W., and Ross, D. (1992). Bioreductive activation of mitomycin C by DT-diaphorase. Biochemistry 31, 7879-7885.
Siegel, D., Bolton, E. M., Burr, J. A., Liebler, D. C., and Ross, D. (1997). The reduction of alpha-tocopherolquinone by human NAD(P)H: quinone oxidoreductase: the role of alpha-tocopherolhydroquinone as a cellular antioxidant. Mol. Pharmacol. 52, 300-305.
Siegel, D., Gibson, N. W., Preusch, P. C., and Ross, D. (1990). Metabolism of mitomycin C by DT-diaphorase: role in mitomycin C-induced DNA damage and cytotoxicity in human colon carcinoma cells. Cancer Res. 50, 7483-7489.
Singal, P. K., Li, T., Kumar, D., Danelisen, I., and Iliskovic, N. (2000). Adriamycin-induced heart failure: mechanism and modulation. Mol. Cell Biochem. 207, 77-86.
Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., and Boyd, M. R. (1990). New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 82, 1107-1112.
Snyder, S. H., Jaffrey, S. R., and Zakhary, R. (1998). Nitric oxide and carbon monoxide: parallel roles as neural messengers. Brain Res. Brain Res. Rev. 26, 167-175.
Stocker, R., Yamamoto, Y., McDonagh, A. F., Glazer, A. N., and Ames, B. N. (1987). Bilirubin is an antioxidant of possible physiological importance. Science 235, 1043-1046.
Suttner, D. M., Sridhar, K., Lee, C. S., Tomura, T., Hansen, T. N., and Dennery, P. A. (1999). Protective effects of transient HO-1 overexpression on susceptibility to oxygen toxicity in lung cells. Am. J. Physiol 276, L443-L451.
Thomas, D. J., Sadler, A., Subrahmanyam, V. V., Siegel, D., Reasor, M. J., Wierda, D., and Ross, D. (1990). Bone marrow stromal cell bioactivation and detoxification of the benzene metabolite hydroquinone: comparison of macrophages and fibroblastoid cells. Mol. Pharmacol. 37, 255-262.
Tomasz, M., Lipman, R., Chowdary, D., Pawlak, J., Verdine, G. L., and Nakanishi, K. (1987). Isolation and structure of a covalent cross-link adduct between mitomycin C and DNA. Science 235, 1204-1208.
Traver, R. D., Horikoshi, T., Danenberg, K. D., Stadlbauer, T. H., Danenberg, P. V., Ross, D., and Gibson, N. W. (1992). NAD(P)H:quinone oxidoreductase gene expression in human colon carcinoma cells: characterization of a mutation which modulates DT-diaphorase activity and mitomycin sensitivity. Cancer Res. 52, 797-802.
Traver, R. D., Siegel, D., Beall, H. D., Phillips, R. M., Gibson, N. W., Franklin, W. A., and Ross, D. (1997). Characterization of a polymorphism in NAD(P)H: quinone oxidoreductase (DT-diaphorase). Br. J. Cancer 75, 69-75.
Tzeng, W. F., Chiou, T. J., Huang, J. Y., and Chen, Y. H. (1992). Menadione-induced cardiotoxicity is associated with alteration in intracellular Ca2+ homeostasis. Proc. Natl. Sci. Counc. Repub. China B 16, 84-90.
Tzeng, W. F., Chiou, T. J., Wang, C. P., Lee, J. L., and Chen, Y. H. (1994). Cellular thiols as a determinant of responsiveness to menadione in cardiomyocytes. J. Mol. Cell Cardiol. 26, 889-897.
Tzeng, W. F., Lee, J. L., and Chiou, T. J. (1995). The role of lipid peroxidation in menadione-mediated toxicity in cardiomyocytes. J. Mol. Cell Cardiol. 27, 1999-2008.
Wang, T. S., Shu, Y. F., Liu, Y. C., Jan, K. Y., and Huang, H. (1997). Glutathione peroxidase and catalase modulate the genotoxicity of arsenite. Toxicology 121, 229-237.
Wang, X., Doherty, G. P., Leith, M. K., Curphey, T. J., and Begleiter, A. (1999). Enhanced cytotoxicity of mitomycin C in human tumour cells with inducers of DT-diaphorase. Br. J. Cancer 80, 1223-1230.
Waxman, S. and Anderson, K. C. (2001). History of the development of arsenic derivatives in cancer therapy. Oncologist. 6 Suppl 2, 3-10.
Wiemels, J. L., Pagnamenta, A., Taylor, G. M., Eden, O. B., Alexander, F. E., and Greaves, M. F. (1999). A lack of a functional NAD(P)H:quinone oxidoreductase allele is selectively associated with pediatric leukemias that have MLL fusions. United Kingdom Childhood Cancer Study Investigators. Cancer Res. 59, 4095-4099.
Wingler, K., Muller, C., Schmehl, K., Florian, S., and Brigelius-Flohe, R. (2000). Gastrointestinal glutathione peroxidase prevents transport of lipid hydroperoxides in CaCo-2 cells. Gastroenterology 119, 420-430.
Winski, S. L., Hargreaves, R. H., Butler, J., and Ross, D. (1998). A new screening system for NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor quinones: identification of a new aziridinylbenzoquinone, RH1, as a NQO1-directed antitumor agent. Clinical Cancer Res.: An Official Journal Of The American Association For Cancer Res. 4, 3083-3088.
Workman, P. and Stratford, I. J. (1993). The experimental development of bioreductive drugs and their role in cancer therapy. Cancer Metastasis Rev. 12, 73-82.
Yachie, A., Niida, Y., Wada, T., Igarashi, N., Kaneda, H., Toma, T., Ohta, K., Kasahara, Y., and Koizumi, S. (1999). Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J. Clin. Invest 103, 129-135.
Yang, P. C., Luh, K. T., Wu, R., and Wu, C. W. (1992). Characterization of the mucin differentiation in human lung adenocarcinoma cell lines. Am. J. Respir. Cell Mol. Biol. 7, 161-171.
Yano, M., Akiyama, Y., Shiozake, H., Inoue, M., Doki, Y., Fujiwara, Y., and Ross, D. (2000). Genetic polymorphism of NAD(P)H:quinone oxidoreductase and mitomycin C sensitivity in gastric caner. Proc. Am. Assoc. Cancer Res. 41, 4-5.
Zhang, J. and Piantadosi, C. A. (1992). Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain. J. Clin. Invest 90, 1193-1199.
Zhu, J., Chen, Z., Lallemand-Breitenbach, V., and de The, H. (2002). How acute promyelocytic leukaemia revived arsenic. Nat. Rev. Cancer 2, 705-713.

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