Chronic inflammation is a well-recognized risk factor for development of human cancer in several tissues, including large bowel. Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer development. Several molecular events involved in chronic inflammatory process may contribute to multistep carcinogenesis of human colorectal cancer in the inflamed colon. They include overproduction of reactive oxygen and nitrogen species, overproduction and upregulation of productions and enzymes of arachidonic acid biosynthesis pathway and cytokines, and intestinal immune system dysfunction. In this paper, I will describe several methods to induce colorectal neoplasm in the inflamed colon. First, I will introduce a protocol of a novel inflammation-associated colon carcinogenesis in mice. In addition, powerful tumor-promotion/progression activity of dextran sodium sulfate in the large bowel of mice will be described. Finally, chemoprevention of inflammation-associated colon carcinogenesis will be mentioned. 1. Introduction Relationship between inflammation and cancer has been suggested for a long time [1]. Since Marshall and Warren [2], who discovered Helicobacter pylori and reported its infection closely associated with gastric cancer development, won the Nobel Prize in Physiology or Medicine in 2005, there have been an increasing number of reports on PubMed as to the relationship between inflammation and carcinogenesis in a variety of tissues (Table 1) and it has been featured in major journals. Table 1: Inflammation and cancer in various tissues. In terms of the large bowel, it has been found that the risk of colorectal cancer increases in relation to the degrees of inflammation and the disease duration (duration/risk = 10 years/1.6%, 20 years/8.3%, and 30 years/18.4%) in inflammatory bowl diseases (IBDs) such as ulcerative colitis (UC) and Crohn’s disease (CD) (Figure 1) [3]. I have been interested in inflammation-associated colorectal carcinogenesis for a long time, since even younger patients with UC have high risk of colorectal cancer [4]. Figure 1: UC patients are high-risk groups of colorectal cancer (CRC) development. Patients with UC as well as those with colorectal cancer have been increasing in Asian countries including Japan, similarly to Western countries (Figure 2) [5]. Therefore, it is necessary to investigate the mechanisms of colorectal cancer development with the background of inflammation for establishing the countermeasure strategy
References
[1]
F. Balkwill and A. Mantovani, “Inflammation and cancer: back to Virchow?” The Lancet, vol. 357, no. 9255, pp. 539–545, 2001.
[2]
B. J. Marshall and J. R. Warren, “Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration,” The Lancet, vol. 1, no. 8390, pp. 1311–1314, 1984.
[3]
J. A. Eaden, K. R. Abrams, and J. F. Mayberry, “The risk of colorectal cancer in ulcerative colitis: a meta-analysis,” Gut, vol. 48, no. 4, pp. 526–535, 2001.
[4]
T. Tanaka, H. Kohno, M. Murakami, R. Shimada, and S. Kagami, “Colitis-related rat colon carcinogenesis induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate (review),” Oncology Reports, vol. 7, no. 3, pp. 501–508, 2000.
[5]
J. J. Y. Sung, J. Y. W. Lau, K. L. Goh et al., “Increasing incidence of colorectal cancer in Asia: implications for screening,” The Lancet Oncology, vol. 6, no. 11, pp. 871–876, 2005.
[6]
T. Tanaka, T. Oyama, and Y. Yasui, “Dietary supplements and colorectal cancer,” Current Topics in Nutraceutical Research, vol. 6, no. 4, pp. 165–188, 2008.
[7]
T. Tanaka and S. Sugie, “Inhibition of colon carcinogenesis by dietary non-nutritive compounds,” Journal of Toxicologic Pathology, vol. 20, no. 4, pp. 215–235, 2007.
[8]
Y. Yasui, M. Kim, T. Oyama, and T. Tanaka, “Colorectal carcinogensis and suppression of tumor development by inhibition of enzymes and molecular targets,” Current Enzyme Inhibition, vol. 5, no. 1, pp. 1–26, 2009.
[9]
T. Tanaka, “Colorectal carcinogenesis: review of human and experimental animal studies,” Journal of Carcinogenesis, vol. 8, article 5, 2009.
[10]
D. W. Rosenberg, C. Giardina, and T. Tanaka, “Mouse models for the study of colon carcinogenesis,” Carcinogenesis, vol. 30, no. 2, pp. 183–196, 2009.
[11]
M. Takahashi and K. Wakabayashi, “Gene mutations and altered gene expression in azoxymethane-induced colon carcinogenesis in rodents,” Cancer Science, vol. 95, no. 6, pp. 475–480, 2004.
[12]
T. Tanaka, H. Kohno, R. Suzuki, Y. Yamada, S. Sugie, and H. Mori, “A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate,” Cancer Science, vol. 94, no. 11, pp. 965–973, 2003.
[13]
A. M. Lefebvre, I. Chen, P. Desreumaux et al., “Activation of the peroxisome proliferator-activated receptor γ promotes the development of colon tumors in C57BL/6J-APCMin/+ mice,” Nature Medicine, vol. 4, no. 9, pp. 1053–1057, 1998.
[14]
E. Saez, P. Tontonoz, M. C. Nelson et al., “Activators of the nuclear receptor PPARγ enhance colon polyp formation,” Nature Medicine, vol. 4, no. 9, pp. 1058–1061, 1998.
[15]
P. Sarraf, E. Mueller, D. Jones et al., “Differentiation and reversal of malignant changes in colon cancer through PPARγ,” Nature Medicine, vol. 4, no. 9, pp. 1046–1052, 1998.
[16]
S. J. Alrawi, M. Schiff, R. E. Carroll et al., “Aberrant crypt foci,” Anticancer Research, vol. 26, no. 1, pp. 107–119, 2006.
[17]
R. P. Bird, “Role of aberrant crypt foci in understanding the pathogenesis of colon cancer,” Cancer Letters, vol. 93, no. 1, pp. 55–71, 1995.
[18]
A. K. Gupta, T. P. Pretlow, and R. E. Schoen, “Aberrant crypt foci: what we know and what we need to know,” Clinical Gastroenterology and Hepatology, vol. 5, no. 5, pp. 526–533, 2007.
[19]
T. Tanaka, H. Kohno, S. I. Yoshitani et al., “Ligands for peroxisome proliferator-activated receptors α and γ inhibit chemically induced colitis and formation of aberrant crypt foci in rats,” Cancer Research, vol. 61, no. 6, pp. 2424–2428, 2001.
[20]
H. Mori, F. Ohbayashi, and I. Hirono, “Absence of genotoxicity of the carcinogenic sulfated polysaccharides carrageenan and dextran sulfate in mammalian DNA repair and bacterial mutagenicity assays,” Nutrition and Cancer, vol. 6, no. 2, pp. 92–97, 1984.
[21]
R. Suzuki, H. Kohno, S. Sugie, and T. Tanaka, “Dose-dependent promoting effect of dextran sodium sulfate on mouse colon carcinogenesis initiated with azoxymethane,” Histology and Histopathology, vol. 20, no. 2, pp. 483–492, 2005.
[22]
R. Suzuki, H. Kohno, S. Sugie, and T. Tanaka, “Sequential observations on the occurrence of preneoplastic and neoplastic lesions in mouse colon treated with azoxymethane and dextran sodium sulfate,” Cancer Science, vol. 95, no. 9, pp. 721–727, 2004.
[23]
H. Kohno, R. Suzuki, S. Sugie, and T. Tanaka, “β-catenin mutations in a mouse model of inflammation-related colon carcinogenesis induced by 1,2-dimethylhydrazine and dextran sodium sulfate,” Cancer Science, vol. 96, no. 2, pp. 69–76, 2005.
[24]
T. Tanaka, R. Suzuki, H. Kohno, S. Sugie, M. Takahashi, and K. Wakabayashi, “Colonic adenocarcinomas rapidly induced by the combined treatment with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate in male ICR mice possess β-catenin gene mutations and increases immunoreactivity for β-catenin, cyclooxygenase-2 and inducible nitric oxide synthase,” Carcinogenesis, vol. 26, no. 1, pp. 229–238, 2005.
[25]
M. M？hler, I. J. Bristol, E. H. Leiter et al., “Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis,” American Journal of Physiology, vol. 274, no. 3, pp. G544–G551, 1998.
[26]
R. Suzuki, H. Kohno, S. Sugie, H. Nakagama, and T. Tanaka, “Strain differences in the susceptibility to azoxymethane and dextran sodium sulfate-induced colon carcinogenesis in mice,” Carcinogenesis, vol. 27, no. 1, pp. 162–169, 2006.
[27]
K. Hata, T. Tanaka, H. Kohno et al., “β-Catenin-accumulated crypts in the colonic mucosa of juvenile ApcMin/+ mice,” Cancer Letters, vol. 239, no. 1, pp. 123–128, 2006.
[28]
Y. Yamada, K. Hata, Y. Hirose et al., “Microadenomatous lesions involving loss of Apc heterozygosity in the colon of adult ApcMin/+ mice,” Cancer Research, vol. 62, no. 22, pp. 6367–6370, 2002.
[29]
T. Tanaka, H. Kohno, R. Suzuki et al., “Dextran sodium sulfate strongly promotes colorectal carcinogenesis in ApcMin/+ mice: inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms,” International Journal of Cancer, vol. 118, no. 1, pp. 25–34, 2006.
[30]
T. Tanaka, Y. Yasui, M. Tanaka, T. Tanaka, T. Oyama, and K. W. Rahman, “Melatonin suppresses AOM/DSS-induced large bowel oncogenesis in rats,” Chemico-Biological Interactions, vol. 177, no. 2, pp. 128–136, 2009.
[31]
N. Toyoda-Hokaiwado, Y. Yasui, M. Muramatsu et al., “Chemopreventive effects of silymarin against 1,2-dimethylhydrazine plus dextran sodium sulfate-induced inflammation-associated carcinogenicity and genotoxicity in the colon of gpt delta rats,” Carcinogenesis, vol. 32, no. 10, pp. 1512–1517, 2011.
[32]
K. Yoshimi, T. Tanaka, A. Takizawa et al., “Enhanced colitis-associated colon carcinogenesis in a novel Apc mutant rat,” Cancer Science, vol. 100, no. 11, pp. 2022–2027, 2009.
[33]
H. Kohno, R. Suzuki, M. Curini et al., “Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice,” International Journal of Cancer, vol. 118, no. 12, pp. 2936–2942, 2006.
[34]
T. Tanaka, M. B. de Azevedo, N. Durán et al., “Colorectal cancer chemoprevention by 2 β-cyclodextrin inclusion compounds of auraptene and 4′-geranyloxyferulic acid,” International Journal of Cancer, vol. 126, no. 4, pp. 830–840, 2010.
[35]
T. Oyama, Y. Yasui, S. Sugie, M. Koketsu, K. Watanabe, and T. Tanaka, “Dietary tricin suppresses inflammation-related colon carcinogenesis in male Crj: CD-1 mice,” Cancer Prevention Research, vol. 2, no. 12, pp. 1031–1038, 2009.
[36]
H. Kohno, R. Suzuki, Y. Yasui, S. Miyamoto, K. Wakabayashi, and T. Tanaka, “Ursodeoxycholic acid versus sulfasalazine in colitis-related colon carcinogenesis in mice,” Clinical Cancer Research, vol. 13, no. 8, pp. 2519–2525, 2007.
[37]
H. Kohno, R. Suzuki, S. Sugie, and T. Tanaka, “Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands,” BMC Cancer, vol. 5, article 46, 2005.
[38]
H. Kohno, M. Takahashi, Y. Yasui et al., “A specific inducible nitric oxide synthase inhibitor, ONO-1714 attenuates inflammation-related large bowel carcinogenesis in male ApcMin/+ mice,” International Journal of Cancer, vol. 121, no. 3, pp. 506–513, 2007.
[39]
Y. Yasui, R. Suzuki, S. Miyamoto et al., “A lipophilic statin, pitavastatin, suppresses inflammation-associated mouse colon carcinogenesis,” International Journal of Cancer, vol. 121, no. 10, pp. 2331–2339, 2007.
[40]
R. Suzuki, S. Miyamoto, Y. Yasui, S. Sugie, and T. Tanaka, “Global gene expression analysis of the mouse colonic mucosa treated with azoxymethane and dextran sodium sulfate,” BMC Cancer, vol. 7, article 84, 2007.
[41]
Y. Yasui and T. Tanaka, “Protein expression analysis of inflammation-related colon carcinogenesis,” Journal of Carcinogenesis, vol. 8, article 10, 2009.
[42]
H. Kohno, Y. Totsuka, Y. Yasui et al., “Tumor-initiating potency of a novel heterocyclic amine, aminophenylnorharman in mouse colonic carcinogenesis model,” International Journal of Cancer, vol. 121, no. 8, pp. 1659–1664, 2007.
[43]
K. Hata, T. Tanaka, H. Kohno et al., “Lack of enhancing effects of degraded λ-carrageenan on the development of β-catenin-accumulated crypts in male DBA/2J mice initiated with azoxymethane,” Cancer Letters, vol. 238, no. 1, pp. 69–75, 2006.
[44]
I. Hirono, I. Ueno, and S. Aiso, “Enhancing effect of dextran sulfate sodium on colorectal carcinogenesis by 1,2-dimethylhydrazine in rats,” Gann, vol. 74, no. 4, pp. 493–496, 1983.
[45]
I. Okayasu, M. Yamada, T. Mikami, T. Yoshida, J. Kanno, and T. Ohkusa, “Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced colitis model,” Journal of Gastroenterology and Hepatology, vol. 17, no. 10, pp. 1078–1083, 2002.
