Radical causes of cancer

Nature Reviews Cancer

Volumn 3, Issue 4, 2003, Pages 276-285

  Hussain, S Perwez ^a   Hofseth, Lorne J ^a   Harris, Curtis C ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ALDEHYDE; ALPHA INTERFERON; ALPHA TOCOPHEROL; ANTIOXIDANT; APC PROTEIN; ASCORBIC ACID; BETA INTERFERON; BIOLOGICAL MARKER; CYCLOOXYGENASE 2; CYTOKINE; DIPYRONE; ENZYME; FAS LIGAND; FREE RADICAL; HYDROXYL RADICAL; INTERLEUKIN 10; MALONALDEHYDE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; NONSTEROID ANTIINFLAMMATORY AGENT; PARACETAMOL; PEROXYNITRITE; PHENACETIN; PHENAZONE; PROTEIN P21; PROTEIN P53; SCAVENGER; UNINDEXED DRUG; VASCULOTROPIN; XIAO CHAI HU TANG;

AEROBIC METABOLISM; ANGIOGENESIS; APOPTOSIS; CANCER; CANCER LOCALIZATION; CANCER PREVENTION; CANCER RISK; CARCINOGENESIS; CELL CYCLE; CELL DAMAGE; CELL PROTECTION; CHEMOPROPHYLAXIS; CHRONIC INFLAMMATION; CLINICAL TRIAL; COLON POLYPOSIS; COLORECTAL CANCER; CORRELATION ANALYSIS; CROHN DISEASE; CYTOTOXICITY; DNA DAMAGE; DNA REPAIR; ENTEROCOLITIS; GENE EXPRESSION; GENE MUTATION; GENE REPRESSION; GENE TARGETING; GENETIC POLYMORPHISM; GENOTYPE ENVIRONMENT INTERACTION; HELICOBACTER INFECTION; HEMOCHROMATOSIS; HEPATITIS B; HEPATITIS C; HOMEOSTASIS; HUMAN; KNOCKOUT MOUSE; LIPID PEROXIDATION; LIVER CARCINOGENESIS; MICROORGANISM; MOLECULAR MECHANICS; NITRATION; NITROSATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN MODIFICATION; PROTEIN PROCESSING; PROTEIN STRUCTURE; REVIEW; TRANSCRIPTION INITIATION; TRANSGENIC ANIMAL; ULCERATIVE COLITIS; VIRUS HEPATITIS; VIRUS INFECTION; ANIMAL; ANIMAL MODEL; BIOSYNTHESIS; GENETICS; INFLAMMATION; METABOLISM; MUTATION; NEOPLASM; TUMOR SUPPRESSOR GENE;

ANIMALS; CHEMOPREVENTION; DNA DAMAGE; FREE RADICALS; GENES, P53; HUMANS; INFLAMMATION; MODELS, ANIMAL; MUTATION; NEOPLASMS; NITRIC OXIDE SYNTHASE;

EID: 0038352053     PISSN: 1474175X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrc1046     Document Type: Review

References (179)

1. Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860-867 (2002).
2. Nathan, C. Points of control in inflammation. Nature 420, 846-852 (2002).
3. Christen, S., Hagen, T. M., Shigenaga, M. K. & Ames, B. N. in Microbes and Malignancy: Infection as a Cause of Cancer 35-88 (Oxford Univ. Press, New York, 1999).
4. Ames, B. N., Gold, L. S. & Willett, W. C. The causes and prevention of cancer. Proc. Natl Acad. Sci. USA 92, 5258-5265 (1995).
5. Cerutti, P. A. & Trump, B. F. Inflammation and oxidative stress in carcinogenesis. Cancer Cells 3, 1-7 (1991).
6. Shalon, D., Smith, S. J. & Brown, P. O. A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. Genome Res. 6, 639-645 (1996).
7. Cerutti, P. A. Prooxidant states and tumor promotion. Science 227, 375-381 (1985).
8. Phillips, L. L. Effect of free radicals on chromosomes of barley. Science 124, 889-890 (1956). Key study showing that free radicals damage DNA.
9. Wiseman, H. & Halliwell, B. Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem. J. 313, 17-29 (1996).
10. Marshall, H. E., Merchant, K. & Stamler, J. S. Nitrosation and oxidation in the regulation of gene expression. FASEB J. 14, 1889-1900 (2000).
11. Aulak, K. S. et al. Proteomic method identifies proteins nitrated in vivo during inflammatory challenge. Proc. Natl Acad. Sci. USA 98, 12056-12061 (2001). Important report of vast protein nitration following an inflammatory challenge in animals.
12. Marnett, L. J. Oxyradicals and DNA damage. Carcinogenesis 21, 361-370 (2000).
13. Whiteman, M., Hooper, D. C., Scott, G. S., Koprowski, H. & Halliwell, B. Inhibition of hypochlorous acid-induced cellular toxicity by nitrite. Proc. Natl Acad. Sci. USA 99, 12061-12066 (2002).
14. Gutteridge, J. M. & Halliwell, B. Free radicals and antioxidants in the year 2000. A histodcal look to the future. Ann. NY Acad. Sci. 899, 136-147 (2000).
15. Beckman, J. S. & Koppenol, W. H. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am. J. Physiol. 271, C1424-C1437 (1996).
16. Espey, M. G. et al. A chemical perspective on the interplay between NO, reactive oxygen species, and reactive nitrogen oxide species. Ann. NY Acad. Sci. 962, 195-206 (2002).
17. Pryor, W. A. Oxy-radicals and related species: their formation, lifetimes, and reactions. Annu. Rev. Physiol. 48, 657-667 (1986).
18. Radi, R. Peroxynitrite reactions and diffusion in biology. Chem. Res. Toxicol. 11, 720-721 (1998).
19. 2. Proc. Natl Acad. Sci. USA 98, 355-360 (2001).
20. Stadtman, E. R. & Levine, R. L. Protein oxidation. Ann. NY Acad. Sci. 899, 191-208 (2000).
21. Eiserich, J. P., Patel, R. P. & O'Donnell, V. B. Pathophysiology of nitric oxide and related species: free radical reactions and modification of biomolecules. Mol. Aspects Med. 19, 221-357 (1998).
22. Squadrito, G. L. & Pryor, W. A. Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide. Free Radic. Biol. Med. 25, 392-403 (1998).
23. Hofseth, L. J. et al. Nitric oxide-induced cellular stress and p53 activation in chronic inflammation. Proc. Natl Acad. Sci. USA 100, 143-148 (2003).
24. Nakaya, N., Lowe, S. W., Taya, Y., Chenchik, A. & Enikolopov, G. Specific pattern of p53 phosphorylation during nitric oxide-induced cell cycle arrest. Oncogene 19, 63696375 (2000).
25. Xu, W., Liu, L., Smith, G. C. & Charles, I. Nitric oxide upregulates expression of DNA-PKcs to protect cells from DNA-damaging anti-tumour agents. Nature Cell Biol. 2, 339-345 (2000). Key study showing that nitric oxide activates kinases.
26. Wink, D. A. et al. Chemical biology of nitric oxide: regulation and protective and toxic mechanisms. Curr. Top. Cell Regul. 34, 159-187 (1996).
27. Pervin, S., Singh, R. & Chaudhuri, G. Nitric oxide-induced cytostasis and cell cycle arrest of a human breast cancer cell line (MDA-MB-231): potential role of cyclin D1. Proc. Natl Acad Sci. USA 98, 3583-3588 (2001).
28. Melino, G. et al. S-nitrosylation regulates apoptosis. Nature 388, 432-433 (1997). This report showed that nitric oxide changes the structure and function of key apoptosis proteins.
29. Jaiswal, M., LaRusso, N. F., Nishioka, N., Nakabeppu, Y. & Gores, G. J. Human Ogg1, a protein involved in the repair of 8-oxoguanine, is inhibited by nitric oxide. Cancer Res. 61, 6388-6393 (2001).
30. Wink, D. A. & Laval, J. The Fpg protein, a DNA repair enzyme, is inhibited by the biomediator nitrc oxide in vitro and in vivo. Carcinogenesis 15, 2125-2129 (1994).
31. Jenkins, D. C. et al. Roles of nitric oxide in tumor growth. Proc. Natl Acad. Sci. USA 92, 4392-4396 (1995). Key study showing the dual roles of nitric oxide in animals.
32. Maeda, H., Noguchi, Y., Sato, K. & Akaike, T. Enhanced vascular permeability in solid tumor is mediated by nitric oxide and inhibited by both new nitric oxide scavenger and nitric oxide synthase inhibitor. Jpn. J. Cancer Res. 85, 331-334 (1994).
33. Tozer, G. M., Prise, V. E. & Chaplin, D. J. Inhibition of nitric oxide synthase induces a selective reduction in tumor blood flow that is reversible with L-arginine. Cancer Res. 57, 948-955 (1997).
34. Tamir, S., Burney, S. & Tannenbaum, S. R. DNA damage by nitric oxide. Chem. Res. Toxicol. 9, 821-827 (1996).
35. Ohshima, H. & Bartsch, H. Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat. Res. 305, 253-264 (1994).
36. Wink, D. A. et al. The effect of various nitric oxide-donor agents on hydrogen peroxide-mediated toxicity: a direct correlation between nitric oxide formation and protection. Arch. Biochem. Biophys. 331, 241-248 (1996).
37. Heller, R., Polack, T., Grabner, R. & Till, U. Nitric oxide inhibits proliferation of human endothelial cells via a mechanism independent of cGMP. Atherosclerosis 144, 49-57 (1999).
38. Kanamaru, Y., Takada, T., Saura, R. & Mizuno, K. Effect of nitric oxide on mouse clonal osteogenic cell, MC3T3-E1, proliferation in vitro. Kobe J. Med. Sci. 47, 1-11 (2001).
39. Ulibarri, J. A., Mozdziak, P. E., Schultz, E., Cook, C. & Best, T. M. Nitric oxide donors, sodium nitroprusside and S-nitroso-N-acetylpencillamine, stimulate myoblast proliferation in vitro. In vitro Cell Dev. Biol. Anim. 35, 215-218 (1999).
40. Weller, R., Billiar, T. & Vodovotz, Y. Pro- and anti-apoptotic effects of nitric oxide in irradiated keratinocytes: the role of superoxide. Skin Pharmacol. Appl. Skin Physiol. 15, 348-352 (2002).
41. Nicotera, P., Bonfoco, E. & Brune, B. Mechanisms for nitric oxide-induced cell death: involvement of apoptosis. Adv. Neuroimmunol. 5, 411-420 (1997).
42. Dimmeler, S., Haendeler J., Nehls, M. & Zeiher, A. M. Suppression of apoptosis by nitric oxide via inhibition of interleukin-1β-converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like proteases. J. Exp. Med. 185, 601-607 (1997).
43. Li, J., Bombeck, C. A., Yang, S., Kim, Y. M. & Billiar, T. R. Nitric oxide suppresses apoptosis via interrupting caspase activation and mitochondrial dysfunction in cultured hepatocytes. J. Biol. Chem. 274, 17325-17333 (1999).
44. Kim, Y.-M., Chung, H.-T., Simmons, R. L. & Billiar, T. R. Cellular non-heme iron content is a determinant of nitric oxide-mediated apoptosis, necrosis, and caspase inhibition. J. Biol. Chem. 275, 10954-10961 (2000).
45. Chung, H. T., Pae, H. O., Choi, B. M., Billiar, T. R. & Kim, Y. M. Nitric oxide as a bioregulator of apoptosis. Biochem. Biophys. Res. Commun. 282, 1075-1079 (2001).
46. Melillo, G. et al. A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J. Exp. Med. 182, 1683-1693 (1995).
47. Chen, B. & Deen, W. M. Analysis of the effects of cell spacing and liquid depth on nitric oxide and its oxidation products in cell cultures. Chem. Res. Toxicol. 14, 135-147 (2001).
48. Burney, S., Niles, J. C., Dedon, P. C. & Tannenbaum, S. R. DNA damage in deoxynucleosides and oligonucleotides treated with peroxynitrite. Chem. Res. Toxicol. 12, 513-520 (1999).
49. Burney, S., Caulfield, J. L., Niles, J. C., Wishnok, J. S. & Tannenbaum, S. R. The chemistry of DNA damage from nitric oxide and peroxynitrite. Mutat. Res. 424, 37-49 (1999).
50. Gorsdorf, S., Appel, K. E., Engeholm, C. & Obe, G. Nitrogen dioxide induces DNA single-strand breaks in cultured Chinese hamster cells. Carcinogenesis 11, 37-41 (1990).
51. Schmidt, K., Desch, W., Klatt, P., Kukovetz, W. R. & Mayer, B. Release of nitric oxide from donors with known half-life: a mathematical model for calculating nitric oxide concentrations in aerobic solutions. Naunyn Schmiedebergs Arch. Pharmacol. 355, 457-462 (1997).
52. Hofseth, L. J., Hussain, S. P., Wogan, G. N. & Harris, C. C. Nitric oxide in cancer and chemoprevention. Free Radic. Biol. Med. (in the press).
53. Zhuang, J. C., Wright, T. L., deRojas-Walker, T., Tannenbaum, S. R. & Wogan, G. N. Nitric oxide-induced mutations in the HPRT gene of human lymphoblastoid TK6 cells and in Salmonella typhimurium. Environ. Mol. Mutagen. 35, 39-47 (2000).
54. Zhuang, J. C., Lin, C., Lin, D. & Wogan, G. N. Mutagenesis associated with nitric oxide production in macrophages. Proc. Natl Acad. Sci. USA 95, 8286-8291 (1998).
55. Sibghat-Ullah et al. Base analog and neighboring base effects on substrate specificity of recombinant human G:T mismatch-specific thymine DNA-glycosylase. Biochemistry 35, 12926-12932 (1996).
56. Ambs, S. et al. p53 and vascular endothelial growth factor regulate tumour growth of NOS2-expressing human carcinoma cells. Nature Med. 4, 1371-1376 (1998). The authors showed that a p53 background has a crucial role in dictating the pro- or antitumorigenic effects of nitric oxide.
57. Papapetropoulos, A., Garcia-Cardena, G., Madri, J. A. & Sessa, W. C. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J. Clin. Invest. 100, 3131-3139 (1997). Key study showing that nitric oxide stimulates angiogenesis.
58. Forrester, K. et al. Nitric oxide-induced p53 accumulation and regulation of inducible nitric oxide synthase (NOS2) expression by wild-type p53. Proc. Natl Acad. Sci. USA 93, 2442-2447 (1996).
59. Ambs, S. et al. Upregulation of NOS2 expression in cancer-prone p53 knockout mice. Proc. Natl Acad. Sci. USA 95, 8823-8828 (1998).
60. Ambs, S. et al. Relationship between p53 mutations and inducible nitric oxide synthase expression in human colorectal cancer. J. Natl Cancer Inst. 91, 86-88 (1999).
61. Hussain, S. P. et al. Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease. Cancer Res. 60, 3333-3337 (2000).
62. Hussain, S. P. et al. Increased p53 mutation load in nontumorous human liver of wilson disease and hemochromatosis: oxyradical overload diseases. Proc. Natl Acad. Sci. USA 97, 12770-12775 (2000).
63. Ambs, S. et al. Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression. Cancer Res. 58, 334-341 (1998).
64. Alleva, D. G., Burger, C. J. & Elgert, K. D. Tumor-induced regulation of suppressor macrophage nitric oxide and TNF-alpha production. Role of tumor-derived IL-10, TGF-beta, and prostaglandin E2. J. Immunol. 153, 1674-1686 (1994).
65. Hollstein, M., Sidransky, D., Vogelstein, B. & Harris, C. C. p53 mutations in human cancers. Science 253, 49-53 (1991).
66. Greenblatt, M. S., Bennett, W. P., Hollstein, M. & Harris, C. C. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 54, 4855-4878 (1994).
67. O'Rourke, R. W. et al. A potential transcriptional activation element in the p53 protein. Oncogene 5, 1829-1832 (1990).
68. Thomsen, L. L. et al. Nitric oxide synthase activity in human breast cancer. Br. J. Cancer 72, 41-44 (1995).
69. Ellie, E., Loiseau, H., Lafond, F., Arsaut, J. & Demotes-Mainard, J. Differential expression of inducible nitric oxide synthase mRNA in human brain tumours. Neuroreport 7, 294-296 (1995).
70. Gallo, O. et al. Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer. J. Natl Cancer Inst. 90, 587-596 (1998).
71. Berenblum, I. The cocarcinogenic action of croton resin. Cancer Res. 1, 44-48 (1941).
72. Friedwald, W. F. & Rous, P. The initiating and promoting elements in tumor production: an analysis of the effects of tar, benzpyrene, and methylcholanthrene on rabbit skin. J. Exp. Med. 80, 101-126 (1944). References 71 and 72 are important papers describing a role for chronic irritation and associated inflammation in tumorigenesis in animals.
73. Cooper, H. S. et al. The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium-induced colitis. Gastroenterology 121, 1407-1416 (2001).
74. Hokari. R. et al. Reduced sensitivity of inducible nitric oxide synthase-deficient mice to chronic colitis. Free Radic. Biol. Med. 31, 153-163 (2001).
75. Goldstein, S. R. et al. Development of esophageal metaplasia and adenocarcinoma in a rat surgical model without the use of a carcinogen. Carcinogenesis 18, 2266-2270 (1997).
76. Chen, X. et al. An esophagogastroduodenal anastomosis model for esophageal adenocarcinogenesis in rats and enhancement by iron overload. Carcinogenesis 20, 1801-1808 (1999).
77. Chisari, F. V. et al. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell 59, 1146-1156 (1989). A key paper describing a mechanism by which hepatitis B virus and chronic irritation lead to development of hepatocellular carcinoma in animals.
78. Lee, A. Animal models of Helicobacter infection. Mol. Med. Today 5, 500-501 (1999).
79. Kumar, A. & Creery, W. D. The therapeutic potential of interleukin 10 in infection and inflammation. Arch. Immunol. Ther. Exp. (Warsz.) 48, 529-538 (2000).
80. Kuhn, R., Lohler, J., Rennick, D., Rajewsky, K. & Muller, W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75, 263-274 (1993). Key study describing how the genetic knockout of II-10 leads to colitis in animals.
81. Berg, D. J. et al. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J. Clin. Invest. 98, 1010-1020 (1996).
82. Kullberg, M. C. et al. Helicobacter hepaticus triggers colitis in specific-pathogen-free interleukin-10 (IL-10)-deficient mice through an IL-12- and gamma interferon-dependent mechanism. Infect. Immun. 66, 5157-5166 (1998).
83. MacMicking, J. D. et al. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 81, 641-650 (1995). Key study describing the phenotype of iNOS-knockout mice and showing that iNOS defends the host against infectious agents and tumour cells at the risk of contributing to tissue damage and shock.
84. Mashimo, H. & Goyal, R. K. Lessons from genetically engineered animal models. IV. Nitric oxide synthase gene knockout mice. Am. J. Physiol. 277, G745-G750 (1999).
85. McCafferty, D. M., Miampamba, M., Sihota, E., Sharkey, K. A. & Kubes, P. Role of inducible nitric oxide synthase in trinitrobenzene sulphonic acid induced colitis in mice. Gut 45, 864-873 (1999).
86. Zingarelli, B., Szabo, C. & Salzman, A. L. Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase. Gut 45, 199-209 (1999).
87. Konopka, T. E. et al. Nitric oxide synthase II gene disruption: implications for tumor growth and vascular endothelial growth factor production. Cancer. Res 61, 3182-3187 (2001).
88. Ahn, B. & Ohshima, H. Suppression of intestinal polyposis in Apc(Min/+) mice by inhibiting nitric oxide production. Cancer Res. 61, 8357-8360 (2001).
89. Gupta, R. A. & DuBois, R. N. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nature Rev. Cancer 1, 11-21 (2001).
90. Tiano, H. F. et al. Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. Cancer Res. 62, 3395-3401 (2002).
91. Langenbach, R., Loftin, C. D., Lee, C. & Tiano, H. Cyclooxygenase-deficient mice. A summary of their characteristics and susceptibilities to inflammation and carcinogenesis. Ann. NY Acad. Sci. 889, 52-61 (1999).
92. Chulada, P. C. et al. Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res. 60, 4705-4708 (2000).
93. Williams, C. S., Tsujii, M., Reese, J., Dey, S. K. & DuBois, R. N. Host cyclooxygenase-2 modulates carcinoma growth. J. Clin. Invest. 105, 1589-1594 (2000).
94. Oshima, M. et al. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87, 803-809 (1996).
95. Chandrasekharan, N. V. et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc. Natl Acad. Sci. USA 99, 13926-13931 (2002). An important paper describing another form of cyclooxygenase, COX3.
96. Hofseth, L. J., Hussain, S. P., Wang, X. W. & Harris, C. C. in Gastrointestinal Oncology: Principles and Practice 539-558 (Lippincott Williams & Wilkins, Philadelphia, 2002).
97. Niederau, C. et al. Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N. Engl. J. Med. 313, 1256-1262 (1985).
98. Bomford, A. Genetics of haemochromatosis. Lancet 360, 1673-1681 (2002).
99. Britton, R. S. Metal-induced hepatotoxicity. Semin. Liver Dis. 16, 3-12 (1996).
100. Sagripanti, J. L. DNA damage mediated by metal ions with special reference to copper and iron. Met. Ions. Biol. Syst. 36, 179-209 (1999).
101. Linn, S. DNA damage by iron and hydrogen peroxide in vitro and in vivo. Drug Metab. Rev. 30, 313-326 (1998).
102. Wang, D., Kreutzer, D. A. & Essigmann, J. M. Mutagenicity and repair of oxidative DNA damage: insights from studies using defined lesions. Mutat. Res. 400, 99-115 (1998).
103. Gatei, M. et al. Ataxia telengiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment using phospho-specific antibodies. J. Biol. Chem. 276, 17276-17280 (2001).
104. Bartsch, H. Keynote address: exocyclic adducts as new risk markers for DNA damage in man. IARC Sci. Publ. 150, 1-16 (1999).
105. Nair, J., Barbin, A., Velic, I. & Bartsch, H. Etheno DNA-base adducts from endogenous reactive species. Mutat. Res. 424, 59-69 (1999).
106. Marnett, L. J. Lipid peroxidation-DNA damage by malondialdehyde. Mutat. Res. 424, 83-95 (1999).
107. Niemela, O. et al. Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury. J. Lab Clin. Med. 133, 451-460 (1999).
108. Young, I. S. et al. Antioxidant status and lipid peroxidation in hereditary haemochromatosis. Free Radic. Biol. Med. 16, 393-397 (1994).
109. Nair, J. et al. Lipid peroxidation-induced etheno-DNA adducts in the liver of patients with the genetic metal storage disorders Wilson's disease and primary hemochromatosis. Cancer Epidemiol. Biomarkers Prev. 7, 435-440 (1998).
110. Riddell, R. H. et al. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum. Pathol. 14, 931-968 (1983).
111. Wong, N. A. & Harrison, D. J. Colorectal neoplasia in ulcerative colitis-recent advances. Histopathology 39, 221-234 (2001).
112. O'Sullivan, J. N. et al. Chromosomal instability in ulcerative colitis is related to telomere shortening. Nature Genet. 32, 280-284 (2002).
113. Vogelstein, B. et al. Genetic alterations during colorectal-tumor development. N. Engl. J. Med. 319, 525-532 (1988).
114. Burmer, G. C. et al. Neoplastic progression in ulcerative colitis: histology, DNA content, and loss of a p53 allele. Gastroenterology 103, 1602-1610 (1992).
115. Tarmin, L. et al. Adenomatous polyposis coli gene mutations in ulcerative colitis-associated dysplasias and cancers versus sporadic colon neoplasms. Cancer Res. 55, 2035-2038 (1995).
116. Yin, J. et al. p53 point mutations in dysplastic and cancerous ulcerative colitis lesions. Gastroenterology 104, 1633-1639 (1993).
117. Robinson, W. S. Molecular events in the pathogenesis of hepadnavirus-associated hepatocellular carcinoma. Annu. Rev. Med. 45, 297-323 (1994).
118. Murakami, T., Kim, T. & Nakamura, H. Hepatitis, cirrhosis, and hepatoma. J. Magn. Reson. Imaging 8, 346-358 (1998).
119. Hagen, T. M. et al. Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma. Proc. Natl Acad. Sci. USA 91, 12808-12812 (1994).
120. Mahe, Y. et al. Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements. J. Biol. Chem. 266, 13759-13763 (1991).
121. Hu, K. Q., Yu, C. H. & Vierling, J. M. Up-regulation of intercellular adhesion molecule 1 transcription by hepatitis B virus X protein. Proc. Natl Acad. Sci. USA 89, 11441-11445 (1992).
122. Zhou, D. X., Taraboulos, A., Ou, J. H. & Yen, T. S. Activation of class I major histocompatibility complex gene expression by hepatitis B virus. J. Virol. 64, 4025-4028 (1990).
123. Lara-Pezzi, E. et al. The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression. J. Clin. Invest. 110, 1831-1838 (2002).
124. Majano, P. L. et al. Inducible nitric oxide synthase expression in chronic viral hepatitis. Evidence for a virus-induced gene upregulation. J. Clin. Invest. 101, 1343-1352 (1998).
125. Lee, M. O. et al. Hepatitis B virus X protein induced expression of interleukin 18 (IL-18): a potential mechanism for liver injury caused by hepatitis B virus (HBV) infection. J. Hepatol. 37, 380-386 (2002).
126. Kuo, G. et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244, 362-364 (1989).
127. Choo, Q. L. et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244, 359-362 (1989).
128. Lee, Y. S. et al. Induction of oh8Gua glycosylase in rat kidneys by potassium bromate (KBrO3), a renal oxidative carcinogen. Mutat. Res. 364, 227-233 (1996).
129. Rusyn, I. et al. Expression of base excision repair enzymes in rat and mouse liver is induced by peroxisome proliferators and is dependent upon carcinogenic potency. Carcinogenesis 21, 2141-2145 (2000).
130. Goode, E. L., Ulrich, C. M. & Potter, J. D. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol. Biomarkers Prev. 11, 1513-1530 (2002).
131. Ambrosone, C. B. et al. Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer. Cancer Res. 59, 602-606 (1999).
132. Ratnasinghe, D. et al. Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk. Cancer Res. 60, 6381-6383 (2000).
133. Moldawer, L. L. et al. Application of gene therapy to acute inflammatory diseases. Shock 12, 83-101 (1999).
134. Rosin, M. P. & Hofseth, L. J. in Microbes and Malignancy: Infection as a Cause of Human Cancers 313-345 (Oxford Univ. Press, Oxford, 1999).
135. Ikeda, K. et al. Interferon decreases hepatocellular carcinogenesis in patients with cirrhosis caused by the hepatitis B virus: a pilot study. Cancer 82, 827-835 (1998).
136. Moradpour, D. & Blum, H. E. Current and evolving therapies for hepatitis C. Eur. J. Gastroenterol. Hepatol. 11, 1199-1202 (1999).
137. Gramenzi, A. et al. Impact of interferon therapy on the natural history of hepatitis C virus related cirrhosis. Gut 48, 843-848 (2001).
138. Nishiguchi, S. et al. Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis. Lancet 357, 196-197 (2001). This key prospective study shows that interferon-α inhibits hepatocellular carcinoma that is associated with hepatitis C.
139. Nishiguchi, S. et al. Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 346, 1051-1055 (1995).
140. Fiorucci, S., Antonelli, E., Burgaud, J. L. & Morelli, A. Nitric oxide-releasing NSAIDs: a review of their current status. Drug Safety 24, 801-811 (2001).
141. Rao, C. V. et al. Chemopreventive properties of a selective inducible nitric oxide synthase inhibitor in colon carcinogenesis, administered alone or in combination with celecoxib, a selective cyclooxygenase-2 inhibitor. Cancer Res. 62, 165-170 (2002).
142. Yamamoto, Y. & Gaynor, R. B. Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J. Clin. Invest. 107, 135-142 (2001).
143. Tateishi, M., Takano, H., Hashizume, M., Kabashima, A. & Sugimachi, K. Long-term results of corticosteroid administration via appendicostomy in patients with ulcerative colitis involving the entire colon. Int. Surg. 83, 235-240 (1998).
144. Hamilton, L. C. & Warner, T. D. Interactions between inducible isoforms of nitric oxide synthase and cyclo-oxygenase in vivo: investigations using the selective inhibitors, 1400W and celecoxib. Br. J. Pharmacol. 125, 335-340 (1998).
145. Aguilar, F., Harris, C. C., Sun, T., Hollstein, M. & Cerutti, P. Geographic variation of p53 mutational profile in nonmalignant human liver. Science 264, 1317-1319 (1994).
146. Aguilar, F., Hussain, S. P. & Cerutti, P. Aflatoxin B1 induces the transversion of G→T in codon 249 of the p53 tumor suppressor gene in human hepatocytes. Proc. Natl Acad. Sci. USA 90, 8586-8590 (1993).
147. Hussain, S. P., Aguilar, F. & Cerutti, P. Mutagenesis of codon 248 of the human p53 tumor suppressor gene by N-ethyl-N-nitrosourea. Oncogene 9, 13-18 (1994).
148. Sidransky, D. Emerging molecular markers of cancer. Nature Rev. Cancer 2, 210-219 (2002).
149. Traverso, G. et al. Detection of proximal colorectal cancers through analysis of faecal DNA. Lancet 359, 403-404 (2002).
150. Marnett, L. J. & Plastaras, J. P. Endogenous DNA damage and mutation. Trends Genet 17, 214-221 (2001).
151. Bartsch, H. Studies on biomarkers in cancer etiology and prevention: a summary and challenge of 20 years of interdisciplinary research. Mutat. Res. 462, 255-279 (2000).
152. Subbaramaiah, K. et al. Inhibition of cyclooxygenase-2 gene expression by p53. J. Biol. Chem. 274, 10911-10915 (1999).
153. Gillen, C. D., Walmsley, R. S., Prior, P., Andrews, H. A. & Allan, R. N. Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. Gut 35, 1590-1592 (1994).
154. Ekbom, A., Helmick, C., Zack, M. & Adami, H. O. Ulcerative colitis and colorectal cancer. A population-based study. N. Engl. J. Med. 323, 1228-1233 (1990).
155. Shin, H. R. et al. Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea. Int. J. Epidemiol. 25, 933-940 (1996).
156. Mitchell, H., Drake, M. & Medley, G. Prospective evaluation of risk of cervical cancer after cytological evidence of human papilloma virus infection. Lancet 1, 573-575 (1986).
157. Zhang, Z. F. et al. Helicobacter pylori infection on the risk of stomach cancer and chronic atrophic gastritis. Cancer Detect. Prev. 23, 357-367 (1999).
158. Esrig, D., McEvoy, K. & Bennett, C. J. Bladder cancer in the spinal cord-injured patient with long-term catheterization: a casual relationship? Semin. Urol. 10, 102-108 (1992).
159. Streitz, J. M. Jr. Barrett's esophagus and esophageal cancer. Chest Surg. Clin. N. Am. 4, 227-240 (1994).
160. Bansal, P. & Sonnenberg, A. Pancreatitis is a risk factor for pancreatic cancer. Gastroenterology 109, 247-251 (1995).
161. Oka, H. et al. Prospective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9). Cancer 76, 743-749 (1995). This important prospective study shows the use of TJ-9 as a chemopreventive agent against hepatocellular carcinoma.
162. Correa, P. et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-Helicobacter pylori therapy. J. Natl Cancer Inst. 92, 1881-1888 (2000). Key prospective study showing antioxidants prevent against gastric carcinogenesis that is associated with Helicobacter pylori.
163. Zullo, A. et al. Ascorbic acid and intestinal metaplasia in the stomach: a prospective, randomized study. Aliment. Pharmacol. Ther. 14, 1303-1309 (2000).
164. Rotola, A. et al. Beta-interferon treatment of cervical intraepithelial neoplasia: a multicenter clinical trial. Intervirology 38, 325-331 (1995).
165. Meyskens, F. L. Jr. et al. Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial. J. Natl Cancer Inst. 86, 539-543 (1994).
166. Bansal, P. & Sonnenberg, A. Risk factors of colorectal cancer in inflammatory bowel disease. Am. J. Gastroenterol. 91, 44-48 (1996).
167. Eaden, J., Abrams, K., Ekbom, A., Jackson, E. & Mayberry, J. Colorectal cancer prevention in ulcerative colitis: a case-control study. Aliment. Pharmacol. Ther. 14, 145-153 (2000).
168. Lashner, B. A., Provencher, K. S., Seidner, D. L., Knesebeck, A. & Brzezinski, A. The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. Gastroenterology 112, 29-32 (1997).
169. Moody, G. A., Jayanthi, V., Probert, C. S., Mac, K. H. & Mayberry, J. F. Long-term therapy with sulphasalazine protects against colorectal cancer in ulcerative colitis: a retrospective study of colorectal cancer risk and compliance with treatment in Leicestershire. Eur. J. Gastroenterol. Hepatol. 8, 1179-1183 (1996).
170. Pinczowski, D., Ekbom, A., Baron, J., Yuen, J. & Adami, H. O. Risk factors for colorectal cancer in patients with ulcerative colitis: a case-control study. Gastroenterology 107, 117-120 (1994).
171. Tung, B. Y. et al. Ursodiol use is associated with lower prevalence of colonic neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Ann. Intern. Med. 134, 89-95 (2001).
172. Pan, W. H. et al. Vitamin A, Vitamin E or beta-carotene status and hepatitis B-related hepatocellular carcinoma. Ann. Epidemiol. 3, 217-224 (1993).
173. Yu, M. W. et al. Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. Am J. Epidemiol. 150, 367-374 (1999).
174. Yu, M. W. et al. Plasma carotenoids, glutathione S-transferase M1 and T1 genetic polymorphisms, and risk of hepatocellular carcinoma: independent and interactive effects. Am. J. Epidemiol. 149, 621-629 (1999).
175. van Rossum, T. G., Vulto, A. G., de Man, R. A., Brouwer, J. T. & Schalm, S. W. Glycyrrhizin as a potential treatment for chronic hepatitis C. Aliment. Pharmacol. Ther. 12, 199-205 (1998).
176. Arase, Y. et al. The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer 79, 1494-1500 (1997).
177. Rock, C. L., Michael, C. W., Reynolds, R. K. & Ruffin, M. T. Prevention of cervix cancer. Crit. Rev. Oncol. Hematol. 33, 169-185 (2000).
178. Zaridze, D., Borisova, E., Maximovitch, D. & Chkhikvadze, V. Aspirin protects against gastric cancer: results of a case-control study from Moscow, Russia. Int. J. Cancer 82, 473-476 (1999).
179. Dennis, L. K., Lynch, C. F. & Torner, J. C. Epidemiologic association between prostatitis and prostate cancer. Urology 60, 78-83 (2002).