• 1
    Halliwell, B. and Gutteridge, J. M. C. ( 2007) Free Radicals in Biology and Medicine, 4th ed. Oxford University Press, New York.
  • 2
    Iuchi, K.,Ichimiya, A.,Akashi, A.,Mizuta, T.,Lee, Y.,Tada, H.,Mori, T.,Sawamura, K.,Lee, Y., and Furuse, K. ( 1987) Non-Hodgkin's lymphoma of the pleural cavity developing from long-standing pyothorax. Cancer 60, 17711775.
  • 3
    Gilmour, P.,Brown, D.,Beswick, P.,MacNee, W.,Rahman, I., and Donaldson, K. ( 1997) Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors. Environ. Health. Perspect. 105, 13131317.
  • 4
    Hodgson, J. and Darnton, A. ( 2000) The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure. Ann. Occup. Hyg. 44, 565601.
  • 5
    Uemura, N.,Okamoto, S.,Yamamoto, S.,Matsumura, N.,Yamaguchi, S.,Yamakido, M.,Taniyama, K.,Sasaki, N., and Schlemper, R. ( 2001) Helicobacter pylori infection and the development of gastric cancer. N. Engl. J. Med. 345, 784789.
  • 6
    Naito, Y. and Yoshikawa, T. ( 2005) Carcinogenesis and chemoprevention in gastric cancer associated with helicobacter pylori infection: role of oxidants and antioxidants. J Clin. Biochem. Nutr. 36, 3749.
  • 7
    Collins, R.,Feldman, M., and Fordtran, J. ( 1987) Colon cancer, dysplasia, and surveillance in patients with ulcerative colitis. A critical review. N. Engl. J. Med. 316, 16541658.
  • 8
    Eaden, J.,Abrams, K., and Mayberry, J. ( 2001) The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48, 526535.
  • 9
    Toyokuni, S. ( 1996) Iron-induced carcinogenesis: the role of redox regulation. Free Radic. Biol. Med. 20, 553566.
  • 10
    Elmberg, M.,Hultcrantz, R.,Ekbom, A.,Brandt, L.,Olsson, S.,Olsson, R.,Lindgren, S.,Loof, L.,Stal, P.,Wallerstedt, S.,Almer, S.,Sandberg-Gertzen, H., and Askling, J. ( 2003) Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives. Gastroenterology 125, 17331741.
  • 11
    Grodstein, F.,Speizer, F., and Hunter, D. ( 1995) A prospective study of incident squamous cell carcinoma of the skin in the nurses' health study. J. Natl. Cancer. Inst. 87, 10611066.
  • 12
    Nishigori, C.,Hattori, Y., and Toyokuni, S. ( 2004) Role of reactive oxygen species in skin carcinogenesis. Antioxid. Redox Signal 6, 561570.
  • 13
    Preston, D.,Kusumi, S.,Tomonaga, M.,Izumi, S.,Ron, E.,Kuramoto, A.,Kamada, N.,Dohy, H.,Matsuo, T., and Matsui T. ( 1994) Cancer incidence in atomic bomb survivors. III. Leukemia, lymphoma and multiple myeloma, 1950–1987. Radiat. Res. 137, S6897.
  • 14
    Ikeda, K.,Saitoh, S.,Koida, I.,Arase, Y.,Tsubota, A.,Chayama, K.,Kumada, H., and Kawanishi, M. ( 1993) A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology 18, 4753.
  • 15
    Rouach, H.,Fataccioli, V.,Gentil, M.,French, S.,Morimoto, M., and Nordmann, R. ( 1997) Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology. Hepatology 25, 351355.
  • 16
    Pryor, W. ( 1997) Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity. Environ. Health Perspect. 105, 875882.
  • 17
    Wingo, P.,Ries, L.,Giovino, G.,Miller, D.,Rosenberg, H.,Shopland, D.,Thun, M., and Edwards, B. ( 1999) Annual report to the nation on the status of cancer, 1973–1996, with a special section on lung cancer and tobacco smoking. J. Natl. Cancer Inst. 91, 675690.
  • 18
    Matsui, M.,Nishigori, C.,Toyokuni, S.,Takada, J.,Akaboshi, M.,Ishikawa, M.,Imamura, S., and Miyachi, Y. ( 1999) The role of oxidative DNA damage in human arsenic carcinogenesis: detection of 8-hydroxy-2′-deoxyguanosine in arsenic-related Bowen's disease. J. Invest. Dermatol. 113, 2631.
  • 19
    Chen, C.,Chen, C.,Wu, M., and Kuo, T. ( 1992) Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water. Br. J. Cancer 66, 888892.
  • 20
    Liu, L.,Trimarchi, J.,Navarro, P.,Blasco, M., and Keefe, D. ( 2003) Oxidative stress contributes to arsenic-induced telomere attrition, chromosome instability, and apoptosis. J. Biol. Chem. 278, 3199832004.
  • 21
    Waalkes, M. ( 2000) Cadmium carcinogenesis in review. J. Inorg. Biochem. 79, 241244.
  • 22
    Stohs, S. and Bagchi, D. ( 1995) Oxidative mechanisms in the toxicity of metal ions. Free Radic. Biol. Med. 18, 321336.
  • 23
    Stohs, S.,Bagchi, D.,Hassoun, E., and Bagchi, M. ( 2000) Oxidative mechanisms in the toxicity of chromium and cadmium ions. J. Environ. Pathol. Toxicol. Oncol. 19, 201213.
  • 24
    Langard, S. ( 1990) One hundred years of chromium and cancer: a review of epidemiological evidence and selected case reports. Am. J. Ind. Med. 17, 189215.
  • 25
    Toyokuni, S.,Tanaka, T.,Nishiyama, Y.,Okamoto, K.,Nakashima, Y.,Hamazaki, S.,Okada, S., and Hiai, H. ( 1996) Induction of renal cell carcinoma in male Wistar rats treated with cupric nitrilotriacetate. Lab. Invest. 75, 239248.
  • 26
    Stevens, R. G.,Jones, D. Y.,Micozzi, M. S., and Taylor, P. R. ( 1988) Body iron stores and the risk of cancer. N. Engl. J. Med. 319, 10471052.
  • 27
    Nelson, R. ( 2001) Iron and colorectal cancer risk: human studies. Nutr. Rev. 59, 140148.
  • 28
    Richmond, H. G. ( 1959) Induction of sarcoma in the rat by iron-dextran complex. Br. Med. J. 1, 947949.
  • 29
    Li, J. L.,Okada, S.,Hamazaki, S.,Ebina, Y., and Midorikawa, O. ( 1987) Subacute nephrotoxicity and induction of renal cell carcinoma in mice treated with ferric nitrilotriacetate. Cancer Res. 47, 18671869.
  • 30
    Ebina, Y.,Okada, S.,Hamazaki, S.,Ogino, F.,Li, J. L., and Midorikawa, O. ( 1986) Nephrotoxicity and renal cell carcinoma after use of iron- and aluminum-nitrilotriacetate complexes in rats. J. Natl. Cancer. Inst. 76, 107113.
  • 31
    Ekbom, A.,Helmick, C.,Zack, M., and Adami, H. ( 1990) Increased risk of large-bowel cancer in Crohn's disease with colonic involvement. Lancet 336, 357359.
  • 32
    Lih-Brody, L.,Powell, S.,Collier, K.,Reddy, G.,Cerchia, R.,Kahn, E.,Weissman, G.,Katz, S.,Floyd, R.,McKinley, M.,Fisher, S., and Mullin, G. ( 1996) Increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease. Dig. Dis. Sci. 41, 20782086.
  • 33
    Honda, S.,Fujioka, T.,Tokieda, M.,Satoh, R.,Nishizono, A., and Nasu, M. ( 1998) Development of Helicobacter pylori-induced gastric carcinoma in Mongolian gerbils. Cancer Res. 58, 42554259.
  • 34
    Pignatelli, B.,Bancel, B.,Plummer, M.,Toyokuni, S.,Patricot, L., and Ohshima, H. ( 2001) Helicobacter pylori eradication attenuates oxidative stress in human gastric mucosa. Am. J. Gastroenterol. 96, 17581766.
    Direct Link:
  • 35
    Nozaki, K.,Shimizu, N.,Ikehara, Y.,Inoue, M.,Tsukamoto, T.,Inada, K.,Tanaka, H.,Kumagai, T.,Kaminishi, M., and Tatematsu, M. ( 2003) Effect of early eradication on Helicobacter pylori-related gastric carcinogenesis in Mongolian gerbils. Cancer Sci. 94, 235239.
  • 36
    Saito, I.,Miyamura, T.,Ohbayashi, A.,Harada, H.,Katayama, T.,Kikuchi, S.,Watanabe, Y.,Koi, S.,Onji, M., and Ohta, Y. ( 1990) Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA 87, 65476549.
  • 37
    Kato, J.,Kobune, M.,Nakamura, T.,Kuroiwa, G.,Takada, K.,Takimoto, R.,Sato, Y.,Fujikawa, K.,Takahashi, M.,Takayama, T.,Ikeda, T., and Niitsu, Y. ( 2001) Normalization of elevated hepatic 8-hydroxy-2′-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet. Cancer Res. 61, 86978702.
  • 38
    Papageorgiou, E.,Kostikas, K.,Kiropoulos, T.,Karetsi, E.,Mpatavanis, G., and Gourgoulianis, K. ( 2005) Increased oxidative stress in exudative pleural effusions: a new marker for the differentiation between exudates and transudates? Chest 128, 32913297.
  • 39
    Nakae, D. ( 1999) Endogenous liver carcinogenesis in the rat. Pathol. Int. 49, 10281042.
  • 40
    Kitajima, T.,Hamanaka, H.,Miyachi, Y.,Ono, Y.,Moriguchi, T.,Toyokuni, S., and Imamura, S. ( 1991) Histochemical detection of burn-induced lipid peroxidation in sebaceous glands of rat skin. J.Dermatol. 18, 393396.
  • 41
    Love, R. and Breidahl, A. ( 2000) Acute squamous cell carcinoma arising within a recent burn scar in a 14-year-old boy. Plast. Reconstr. Surg. 106, 10691071.
  • 42
    Clutton, S.,Townsend, K.,Walker, C.,Ansell, J., and Wright, E. ( 1996) Radiation-induced genomic instability and persisting oxidative stress in primary bone marrow cultures. Carcinogenesis 17, 16331639.
  • 43
    Hattori, Y.,Nishigori, C.,Tanaka, T.,Uchida, K.,Nikaido, O.,Osawa, T.,Hiai, H.,Imamura, S., and Toyokuni, S. ( 1996) 8-Hydroxy-2′-deoxyguanosine is increased in epidermal cells of hairless mice after chronic UVB exposure. J. Invest. Dermatol. 107, 733737.
  • 44
    Vogelstein, B. and Kinzler, K. W. ( 1998) The Genetic Basis of Human Cancer. McGraw-Hill, New York.
  • 45
    Toyokuni, S. and Sagripanti, J.-L. ( 1996) Association between 8-hydroxy-2′-deoxyguanosine formation and DNA strand breaks mediated by copper and iron. Free Radic. Biol. Med. 20, 859864.
  • 46
    Toyokuni, S.,Mori, T.,Hiai, H., and Dizdaroglu, M. ( 1995) Treatment of Wistar rats with a renal carcinogen, ferric nitrilotriacetate, causes DNA-protein cross-linking between thymine and tyrosine in their renal chromatin. Int. J. Cancer 62, 309313.
  • 47
    Steenken, S. ( 1989) Purine bases, nucleosides, and nucleotides: aqueous solution redox chemistry and transformation reactions of their radical reactions and e and OH adducts. Chem. Rev. 89, 503520.
  • 48
    Dizdaroglu, M. ( 1991) Chemical determination of free radical-induced damage to DNA. Free Radic. Biol. Med. 10, 225242.
  • 49
    Ohshima, H.,Tatemichi, M., and Sawa, T. ( 2003) Chemical basis of inflammation-induced carcinogenesis. Arch. Biochem. Biophys. 417, 311.
  • 50
    Nakabeppu, Y. ( 2001) Regulation of intracellular localization of human MTH1, OGG1, and MYH proteins for repair of oxidative DNA damage. Prog. Nucleic Acid Res. Mol. Biol. 68, 7594.
  • 51
    Futreal, P.,Coin, L.,Marshall, M.,Down, T.,Hubbard, T.,Wooster, R.,Rahman, N., and Stratton, M. ( 2004) A census of human cancer genes. Nat. Rev. Cancer 4, 177183.
  • 52
    Kantarjian, H.,Sawyers, C.,Hochhaus, A.,Guilhot, F.,Schiffer, C.,Gambacorti-Passerini, C.,Niederwieser, D.,Resta, D.,Capdeville, R.,Zoellner, U.,Talpaz, M.,Druker, B.,Goldman, J.,O'Brien, S.,Russell, N.,Fischer, T.,Ottmann, O.,Cony-Makhoul, P.,Facon, T.,Stone, R.,Miller, C.,Tallman, M.,Brown, R.,Schuster, M.,Loughran, T.,Gratwohl, A.,Mandelli, F.,Saglio, G.,Lazzarino, M.,Russo, D.,Baccarani, M., and Morra, E. ( 2002) Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N. Engl. J. Med. 346, 645652.
  • 53
    Hirota, S.,Isozaki, K.,Moriyama, Y.,Hashimoto, K.,Nishida, T.,Ishiguro, S.,Kawano, K.,Hanada, M.,Kurata, A.,Takeda, M.,Muhammad Tunio, G.,Matsuzawa, Y.,Kanakura, Y.,Shinomura, Y., and Kitamura, Y. ( 1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279, 577580.
  • 54
    Demetri, G.,von Mehren, M.,Blanke, C.,Van den Abbeele, A.,Eisenberg, B.,Roberts, P.,Heinrich, M.,Tuveson, D.,Singer, S.,Janicek, M.,Fletcher, J.,Silverman, S.,Silberman, S.,Capdeville, R.,Kiese, B.,Peng, B.,Dimitrijevic, S.,Druker, B.,Corless, C.,Fletcher, C., and Joensuu, H. ( 2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med. 347, 472480.
  • 55
    Baselga, J.,Norton, L.,Albanell, J.,Kim, Y., and Mendelsohn, J. ( 1998) Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res. 58, 28252831.
  • 56
    Slamon, D.,Leyland-Jones, B.,Shak, S.,Fuchs, H.,Paton, V.,Bajamonde, A.,Fleming, T.,Eiermann, W.,Wolter, J.,Pegram, M.,Baselga, J., and Norton, L. ( 2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783792.
  • 57
    Kantarjian, H.,Talpaz, M.,O'Brien, S.,Giles, F.,Garcia-Manero, G.,Faderl, S.,Thomas, D.,Shan, J.,Rios, M., and Cortes, J. ( 2003) Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood 101, 473475.
  • 58
    Kitano, H. ( 2004) Cancer as a robust system: implications for anticancer therapy. Nat. Rev. Cancer 4, 227235.
  • 59
    Toyokuni, S.,Okamoto, K.,Yodoi, J., and Hiai, H. ( 1995) Persistent oxidative stress in cancer. FEBS Lett. 358, 13.
  • 60
    Loeb, L. A. ( 1991) Mutator phenotype may be required for mutistage carcinogenesis. Cancer Res. 51, 30753079.
  • 61
    Feinberg, A.,Ohlsson, R., and Henikoff, S. ( 2006) The epigenetic progenitor origin of human cancer. Nat. Rev. Genet. 7, 2133
  • 62
    Tanaka, T.,Iwasa, Y.,Kondo, S.,Hiai, H., and Toyokuni, S. ( 1999) High incidence of allelic loss on chromosome 5 and inactivation of p15INK4B and p16INK4A tumor suppressor genes in oxystress-induced renal cell carcinoma of rats. Oncogene 18, 37933797.
  • 63
    Sen, C. and Packer, L. ( 1996) Antioxidant and redox regulation of gene transcription. FASEB J. 10, 709720.
  • 64
    Nakamura, H.,Nakamura, K., and Yodoi, J. ( 1997) Redox regulation of cellular activation. Annu. Rev. Immunol. 15, 351369.
  • 65
    Nishiyama, A.,Matsui, M.,Iwata, S.,Hirota, K.,Masutani, H.,Nakamura, H.,Takagi, Y.,Sono, H.,Gon, Y., and Yodoi, J. ( 1999) Identification of thioredoxin-binding protein-2/vitamin D3 up-regulated protein 1 as a negative regulator of thioredoxin function and expression. J. Biol. Chem. 274, 2164521650.
  • 66
    Nishinaka, Y.,Nishiyama, A.,Masutani, H.,Oka, S.,Ahsan, K.,Nakayama, Y.,Ishii, Y.,Nakamura, H.,Maeda, M., and Yodoi, J. ( 2004) Loss of thioredoxin-binding protein-2/vitamin D3 up-regulated protein 1 in human T-cell leukemia virus type I-dependent T-cell transformation: implications for adult T-cell leukemia leukemogenesis. Cancer Res. 64, 12871292.
  • 67
    Ahsan, M.,Masutani, H.,Yamaguchi, Y.,Kim, Y.,Nosaka, K.,Matsuoka, M.,Nishinaka, Y.,Maeda, M., and Yodoi, J. ( 2005) Loss of interleukin-2-dependency in HTLV-I-infected T cells on gene silencing of thioredoxin-binding protein-2. Oncogene 5, 21812191.
  • 68
    Ikarashi, M.,Takahashi, Y.,Ishii, Y.,Nagata, T.,Asai, S., and Ishikawa, K. ( 2002) Vitamin D3 up-regulated protein 1 (VDUP1) expression in gastrointestinal cancer and its relation to stage of disease. Anticancer Res. 22, 40454048.
  • 69
    Han, S.,Jeon, J.,Ju, H.,Jung, U.,Kim, K.,Yoo, H.,Lee, Y.,Song, K.,Hwang, H.,Na, Y.,Yang, Y.,Lee, K., and Choi, I. ( 2003) VDUP1 upregulated by TGF-β1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression. Oncogene 22, 40354046.
  • 70
    Dutta, K. K.,Nishinaka, Y.,Masutani, H.,Akatsuka, S.,Aung, T. T.,Shirase, T.,Lee, W.-H.,Hiai, H.,Yodoi, J., and Toyokuni, S. ( 2005) Two distinct mechanisms for loss of thioredoxin-biding protein-2 in oxidative stress-induced renal carcinogenesis. Lab. Invest. 85, 798807.
  • 71
    Goldberg, S.,Miele, M.,Hatta, N.,Takata, M.,Paquette-Straub, C.,Freedman, L., and Welch, D. ( 2003) Melanoma metastasis suppression by chromosome 6: evidence for a pathway regulated by CRSP3 and TXNIP. Cancer Res. 63, 432440.
  • 72
    Bodnar, J.,Chatterjee, A.,Castellani, L.,Ross, D.,Ohmen, J.,Cavalcoli, J.,Wu, C.,Dains, K.,Catanese, J.,Chu, M.,Sheth, S.,Charugundla, K.,Demant, P.,West, D.,de Jong, P., and Lusis, A. ( 2002) Positional cloning of the combined hyperlipidemia gene Hyplip1. Nat. Genet. 30, 110116.
  • 73
    Hui, T.,Sheth, S.,Diffley, J.,Potter, D.,Lusis, A.,Attie, A., and Davis, R. ( 2004) Mice lacking thioredoxin Interacting protein provide evidence linking cellular redox state to appropriate response to nutritional signals. J. Biol. Chem. 279, 2438724393.
  • 74
    Oka, S.,Liu, W.,Masutani, H.,Hirata, H.,Shinkai, Y.,Yamada, S.,Yoshida, T.,Nakamura, H., and Yodoi, J. ( 2005) Impaired fatty acid utilization in thioredoxin binding protein-2 (TBP-2)-deficient mice: a unique animal model of Reye syndrome. FASEB J. 147, 733743.
  • 75
    Hockel, M. and Vaupel, P. ( 2001) Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J. Natl. Cancer Inst. 93, 266276.
  • 76
    Endo, K.,Oriuchi, N.,Higuchi, T.,Iida, Y.,Hanaoka, H.,Miyakubo, M.,Ishikita, T., and Koyama, K. ( 2006) PET and PET/CT using 18F-FDG in the diagnosis and management of cancer patients. Int J. Clin. Oncol. 11, 286296.
  • 77
    Nishiyama, Y.,Suwa, H.,Okamoto, K.,Fukumoto, M.,Hiai, H., and Toyokuni, S. ( 1995) Low incidence of point mutations in H-, K- and N-ras oncogenes and p53 tumor suppressor gene in renal cell carcinoma and peritoneal mesothelioma of Wistar rats induced by ferric nitrilotriacetate. Jpn. J. Cancer Res 86, 11501158.
  • 78
    Toyokuni, S. ( 1999) Reactive oxygen species-induced molecular damage and its application in pathology. Pathol. Int. 49, 91102.
  • 79
    Toyokuni, S.,Mori, T., and Dizdaroglu, M. ( 1994) DNA base modifications in renal chromatin of Wistar rats treated with a renal carcinogen, ferric nitrilotriacetate. Int. J. Cancer 57, 123128.
  • 80
    Tanaka, T.,Nishiyama, Y.,Okada, K.,Hirota, K.,Matsui, M.,Yodoi, J.,Hiai, H., and Toyokuni, S. ( 1997) Induction and nuclear translocation of thioredoxin by oxidative damage in the mouse kidney: independence of tubular necrosis and sulfhydryl depletion. Lab. Invest. 77, 145155.
  • 81
    Toyokuni, S.,Uchida, K.,Okamoto, K.,Hattori-Nakakuki, Y.,Hiai, H., and Stadtman, E. R. ( 1994) Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate. Proc. Natl. Acad. Sci. USA 91, 26162620.
  • 82
    Toyokuni, S.,Luo, X. P.,Tanaka, T.,Uchida, K.,Hiai, H., and Lehotay, D. C. ( 1997) Induction of a wide range of C2–12 aldehydes and C7–12 acyloins in the kidney of Wistar rats after treatment with a renal carcinogen, ferric nitrilotriacetate. Free Radic. Biol. Med. 22, 10191027.
  • 83
    Ozeki, M.,Miyagawa-Hayashino, A.,Akatsuka, S.,Shirase, T.,Lee, W.,Uchida, K., and Toyokuni, S. ( 2005) Susceptibility of actin to modification by 4-hydroxy-2-nonenal. J Chromatogr B Analyt Technol Biomed Life Sci 827, 119126.
  • 84
    Uchida, K. ( 2005) Protein-bound 4-hydroxy-2-nonenal as a marker of oxidative stress. J. Clin. Biochem. Nutr. 36, 110.
  • 85
    Jiang, L.,Zhong, Y.,Akatsuka, S.,Liu, Y.,Dutta, K.,Lee, W.,Onuki, J.,Masumura, K.,Nohmi, T., and Toyokuni, S. ( 2006) Deletion and single nucleotide substitution at G:C in the kidney of gpt delta transgenic mice after ferric nitrilotriacetate treatment. Cancer Sci. 97, 11591167.
  • 86
    Lynch, M. and Walsh, B. ( 1998) Genetics and Analysis of Quantitative Traits. Sinauer Associates, Sunderland, Massachusetts.
  • 87
    Kamijo, T.,Weber, J. D.,Zambetti, G.,Zindy, F.,Roussel, M. F., and Sherr, C. J. ( 1998) Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2. Proc. Natl. Acad. Sci. USA 95, 82928297.
  • 88
    Honda, R. and Yasuda, H. ( 1999) Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53. EMBO J. 18, 2227.
  • 89
    Chan, F. K.,Zhang, J.,Cheng, L.,Shapiro, D. N., and Winoto, A. ( 1995) Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4. Mol. Cell. Biol. 15, 26822688.
  • 90
    Hiroyasu, M.,Ozeki, M.,Kohda, H.,Echizenya, M.,Tanaka, T.,Hiai, H., and Toyokuni, S. ( 2002) Specific allelic loss of p16INK4A tumor suppressor gene after weeks of iron-mediated oxidative damage during rat renal carcinogenesis. Am. J. Pathol. 160, 419424.
  • 91
    Liu, Y.-T.,Shang, D.-G.,Akatsuka, S.,Ohara, H.,Dutta, K. K.,Mizushima, K.,Naito, Y.,Yoshikawa, T.,Izumiya, M.,Abe, K.,Nakagama, H.,Noguchi, N., and Toyokuni, S. ( 2007) Chronic oxidative stress causes amplification and overexpresson of ptprz1 protein tyrosine phosphatase to activate β-catenin pathway. Am. J. Pathol. 171, 19781988.
  • 92
    Oikawa, S. and Kawanishi, S. ( 1999) Site-specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening. FEBS Lett. 453, 365368.
  • 93
    von Zglinicki, T.,Pilger, R., and Sitte, N. ( 2000) Accumulation of single-strand breaks is the major cause of telomere shortening in human fibroblasts. Free Radic. Biol. Med. 28, 6474.
  • 94
    Toyokuni, S.,Tanaka, T.,Hattori, Y.,Nishiyama, Y.,Ochi, H.,Hiai, H.,Uchida, K., and Osawa, T. ( 1997) Quantitative immunohistochemical determination of 8-hydroxy-2′-deoxyguanosine by a monoclonal antibody N45.1: its application to ferric nitrilotriacetate-induced renal carcinogenesis model. Lab. Invest. 76, 365374.
  • 95
    Kawai, Y.,Furuhata, A.,Toyokuni, S.,Aratani, Y., and Uchida, K. ( 2003) Formation of acrolein-derived 2′-deoxyadenosine adduct in an iron-induced carcinogenesis model. J. Biol. Chem. 278, 5034650354.
  • 96
    Akatsuka, S.,Aung, T. T.,Dutta, K. K.,Jiang, L.,Lee, W. H.,Liu, Y. T.,Onuki, J.,Shirase, T.,Yamasaki, K.,Ochi, H.,Naito, Y.,Yoshikawa, T.,Kasai, H.,Tominaga, Y.,Sakumi, K.,Nakabeppu, Y.,Kawai, Y.,Uchida, K.,Yamasaki, A.,Tsuruyama, T.,Yamada, Y., and Toyokuni, S. ( 2006) Contrasting genome-wide distribution of 8-hydroxyguanine and acrolein-modified adenine during oxidative stress-induced renal carcinogenesis. Am. J. Pathol. 169, 13281342.
  • 97
    Cremer, T. and Cremer, C. ( 2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat. Rev. Genet. 2, 292301.
  • 98
    Tanabe, H.,Muller, S.,Neusser, M.,von Hase, J.,Calcagno, E.,Cremer, M.,Solovei, I.,Cremer, C., and Cremer, T. ( 2002) Evolutionary conservation of chromosome territory arrangements in cell nuclei from higher primates. Proc. Natl. Acad. Sci. USA 99, 44244429.
  • 99
    Parada, L.,McQueen, P., and Misteli, T. ( 2004) Tissue-specific spatial organization of genomes. Genome Biol. 5, R44.
  • 100
    Steinmetz, K. and Potter, J. ( 1996) Vegetables, fruit, and cancer prevention: a review. J. Am. Diet Assoc. 96, 10271039.
  • 101
    Siddiqui, I.,Afaq, F.,Adhami, V.,Ahmad, N., and Mukhtar, H. ( 2004) Antioxidants of the beverage tea in promotion of human health. Antioxid. Redox Signal 6, 571582.