Induction of colorectal squamous cell carcinomas in rats by dextran sulfate sodium

Hirono, Iwao; Kuhara, Kazunori; Yamaji, Taketo; Hosaka, Shigetoshi; Golberg, L.

doi:10.1093/carcin/3.3.353

Cited by 33 publications

(26 citation statements)

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“…24) DSS is a non-genotoxic carcinogen in colon. 25) For induction of colitis-related colonic tumors in mice by DSS treatment, long-term administration or repeated-cycle treatment is required. In our previous studies using male F344 rats, treatment with AOM during or after DSS exposure could induce a substantial number of ACF.…”

Section: Discussionmentioning

confidence: 99%

A novel inflammation‐related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate

et al. 2003

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To develop an efficient animal model for colitis-related carcinogenesis, male Crj: CD-1 (ICR) mice were given a single intraperitoneal administration (10 mg/kg body weight) of a genotoxic colonic carcinogen, azoxymethane (AOM), and a 1-week oral exposure (2% in drinking water) to a non-genotoxic carcinogen, dextran sodium sulfate (DSS), under various protocols. At week 20, colonic neoplasms (adenocarcinomas, 100% incidence with 5.60 ± ± ± ±2.42 multiplicity; and adenomas, 38% incidence with 0.20 ± ± ± ±0.40 multiplicity) with dysplastic lesions developed in mice treated with AOM followed by DSS. Protocols in which AOM was given during or after DSS administration induced a few tubular adenomas or no tumors in the colon. Immunohistochemical investigation of such dysplasias and neoplasms revealed that all lesions were positive for β β β β-catenin, cyclooxygenase-2 and inducible nitric oxide synthase, but did not show p53 immunoreactivity. The results indicate that 1-week administration of 2% DSS after initiation with a low dose of AOM exerts a powerful tumor-promoting activity in colon carcinogenesis in male ICR mice, and may provide a novel mouse model for investigating colitis-related colon carcinogenesis and for identifying xenobiotics with modifying effects. (Cancer Sci 2003; 94: 965-973) n the developed world, colorectal cancer (CRC) is one of the commonest non-smoking related cancers. This malignancy is one of the most serious complications of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), 1,2) and the risk of CRC increases with increasing extent and duration of the disease.Animal experiments are assumed to simulate or at least provide plausible pathophysiological mechanisms in various diseases including cancer and inflammatory disorders. For IBD and IBD-related CRC, several animal models have been reported. The most widely used is a mouse model with dextran sodium sulfate (DSS).3) There are a number of reports on modifying effects of xenobiotics on CRC-related colon carcinogenesis in this model 4,5) : folic acid, short chain fatty acid (butyrate), ursodeoxycholic acid, nonsteroidal anti-inflammatory drugs (NSAIDs)/cyclooxygenase (COX)-2 inhibitors, and 5-aminosalicylic acid (5-ASA) were found to inhibit the occurrence of UC-related CRC. However, this colitis model using DSS with or without carcinogen needs a long period or repeated administration of DSS to induce colitis and colitis-related CRC, and the incidence and/or multiplicity of induced tumors are relatively low.6) Many studies have suggested that chronic or repeated mucosal inflammation may result in carcinogenesis through mechanisms such as induction of genetic mutations, increased cryptal cell proliferation, changes in crypt cell metabolism, changes in bile acid enterohepatic circulation, and alterations in bacteria flora. 7,8) These ideas are consistent with the hypothesis that chronic inflammation could be associated with epithelial malignant neoplasia in the large bowel. 8) We recently reported c...

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Section: Discussionmentioning

confidence: 99%

A novel inflammation‐related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate

et al. 2003

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“…[12][13][14][15][16]29,35,36 Furthermore, the induction of colitis in severe combined immunodeficient, CD4 ϩ -T cell depleted, and athymic mice by DSS reveals that thymusdependent T cells are not a prerequisite for the colitis 37,38 This has led to the suggestions that DSS-induced colitis is either a macrophage-driven event 39,40 (which fits with a pivotal role for TNF-␣), or because of direct epithelial cytotoxicity/inhibition of proliferation. 37,41,42 Thus, we sought to examine the affect of ROL therapy on TNF-␣ levels and epithelial viability.…”

Section: Discussionmentioning

confidence: 99%

Dextran Sulfate Sodium-Induced Colonic Histopathology, but not Altered Epithelial Ion Transport, Is Reduced by Inhibition of Phosphodiesterase Activity

Diaz-Granados¹,

Howe²,

Lü³

et al. 2000

The American Journal of Pathology

117

100

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Inhibition of phosphodiesterase (PDE) activity is beneficial in models of arthritis and airway inflammation.Here we assessed the ability of PDE inhibitors to modulate colitis by exposing mice to 4% (w/v) dextran sulfate sodium (DSS) drinking water for 5 days with or without rolipram, an inhibitor of PDE type 4, or the nonselective PDE inhibitor, pentoxifylline (both at 5 mg/kg, i.p., twice daily). Controls received saline, vehicle, or drug only. Colonic histology, myeloperoxidase (MPO) and tumor necrosis factor-␣ (TNF-␣) levels, and epithelial ion transport (baseline and stimulated by electrical nerve stimulation, carbachol, and forskolin) were examined. DSS-treated mice displayed a variable diarrhea, significant histopathology in the mid-distal colon, elevated MPO activity, and reduced (>50%) responses to all three pro-secretory stimuli. Treatment with rolipram, and to a lesser extent pentoxifylline, significantly reduced the severity of the colonic histopathology and MPO levels. Neither PDE inhibitor had any affect on the diminished ion transport events caused by DSS-induced colitis. However, although stimulated ion transport events were still reduced 3 days after DSS treatment, colonic segments from DSS ؉ rolipram-treated mice displayed enhanced recovery in their secretory responsiveness, particularly to carbachol. These findings indicate that specific PDE4 inhibition can significantly reduce the tissue damage that accompanies colitis and enhance recovery of normal colonic function.

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“…Intestinal tumors in rats fed 5% DSS in the diet developed between 134 and 215 days. 13) Colorectal carcinomas developed in rats fed DSS for as long as 6 months. 14) Recently, Cooper et al 15) reported a relationship between the severity of DSS-induced inflammation and colorectal carcinogenesis which is similar to that of human UC-associated dysplasia and cancer regarding histopathology.…”

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confidence: 99%

Sequential observations on the occurrence of preneoplastic and neoplastic lesions in mouse colon treated with azoxymethane and dextran sodium sulfate

et al. 2004

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Previously, we proposed a novel mouse model for colitis-related colon carcinogenesis using azoxymethane (AOM) and dextran sodium sulfate (DSS) (Cancer Sci 2003; 94: 965-73). In the current study, sequential analysis of pathological alterations during carcinogenesis in our model was conducted to establish the influence of inflammation caused by DSS on colon carcinogenesis in this model. Male ICR mice were given a single intraperitoneal injection of AOM (10 mg/kg body weight) and given 2% (w/v) DSS in the drinking water for 7 days, starting 1 week after the AOM injection. They were sequentially sacrificed at weeks 2, 3, 4, 5, 6, 9, 12, and 14 for histopathological and immunohistochemical examinations. Colonic adenomas were found in 2 (40% incidence and 0.40 ± ± ± ±0.49 multiplicity) of 5 mice at week 3 and colon carcinomas developed in 2 (40% incidence and 2.00 ± ± ± ±3.52 multiplicity) of 5 mice at week 4. Their incidence gradually increased with time and reached 100% (6.20 ± ± ± ±2.48 multiplicity) at week 6. At week 14, the multiplicity of adenocarcinoma was 9.75 ± ± ± ±2.49 (100% incidence). In addition, colonic dysplasia was noted at all time-points. The scores of colonic inflammation and nitrotyrosine immunohistochemistry were extremely high at early time-points and were well correlated. Our results suggest that combined treatment of mice with AOM and DSS generates neoplasms in the colonic mucosa via dysplastic lesions induced by nitrosative stress. (Cancer Sci 2004; 95: 721-727) n the developed countries, colorectal cancer (CRC) is one of the commonest non-smoking related causes of cancer deaths. Remarkable differences in the incidence worldwide have led to the hypothesis that this variation could be explained largely by environmental influences. 1)The occurrence of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is affected by several factors, including race and geography.2, 3) Life style, particularly intake of high amount of animal fat, is involved in the occurrence of IBD. 4) Over recent decades the incidence of IBD has been rising throughout the world, including Japan, as it has been in the last 50 years in Europe and North America.5) This increase may be caused by increased intake of animal fat. 6) CRC is one of the most serious complications of IBD, especially UC and CD. The risk of CRC becomes greater with increasing extent and duration of the disease. A recent meta-analysis has estimated the incidence rate at 7 per 1000 person-years duration and 12 per 1000 persons per year duration in the second and third decades of UC, respectively.7) The risk for CRC development in CD patients is also high.8) The highest risk of CRC in CD patients was reported to be 26.6 (standardized incidence ratio), although the estimate applied only to patients younger than 21 years of age. 9) Gillen et al. 10)compared the CRC risk in patients with UC and CD and found an 18-fold increase in the risk of developing CRC in extensive CD and a 19-fold increase in risk in extensive...

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Induction of colorectal squamous cell carcinomas in rats by dextran sulfate sodium

Cited by 33 publications

References 0 publications

A novel inflammation‐related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate

A novel inflammation‐related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate

Dextran Sulfate Sodium-Induced Colonic Histopathology, but not Altered Epithelial Ion Transport, Is Reduced by Inhibition of Phosphodiesterase Activity

Sequential observations on the occurrence of preneoplastic and neoplastic lesions in mouse colon treated with azoxymethane and dextran sodium sulfate

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