Absence of genotoxicity of the carcinogenic sulfated polysaccharides carrageenan and dextran sulfate in mammalian DNA repair and bacterial mutagenicity assays

Mori, Hideki; Ohbayashi, Futoshi; Hirono, Iwao; Shimada, Tomiko; Williams, Gary M.

doi:10.1080/01635588509513812

Cited by 33 publications

(18 citation statements)

References 11 publications

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“…Although DSS is not in itself a genotoxic agent (Mori et al, 1984), long-term repeated DSS treatment induced colorectal tumors in wild-type mice (Seril et al, 2002). The risk of cancer is increased under chronic inflammatory conditions including UC.…”

Section: Discussionmentioning

confidence: 99%

Effects of co-treatment of dextran sulfate sodium and MeIQx on genotoxicity and possible carcinogenicity in the colon of p53-deficient mice

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Effects of co-treatment of dextran sulfate sodium and MeIQx on genotoxicity and possible carcinogenicity in the colon of p53-deficient mice

et al. 2010

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“…Since DSS is a nongenotoxic carcinogen [20], male ICR mice were divided into three groups that received different administration patterns: DSS→AOM, AOM during DSS administration, and AOM→DSS (Figure 5). In the groups of DSS→AOM and AOM→DSS, there was a one-week interval between the treatments [12].…”

Section: Development Of An Inflammation-associated Colorectal Cancmentioning

confidence: 99%

“…Treatment with DSS (1% in diet) after DMH exposure produces colonic adenocarcinoma [44]. The tumorigenicityof DSS is non-genotoxic effects [20]. Cycle treatment with 3% DSS (MW 54,000, 7 days) and distilled water (14 days) produces colonic tumors [45].…”

Section: Figurementioning

confidence: 99%

Development of an Inflammation-Associated Colorectal Cancer Model and Its Application for Research on Carcinogenesis and Chemoprevention

Tanaka

2012

International Journal of Inflammation

105

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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 Apc Min/+ mice will be described. Finally, chemoprevention of inflammation-associated colon carcinogenesis will be mentioned.

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“…Most used is an animal model with dextran sodium sulfate (DSS) administration through the diet, or drinking fluid. A nongenotoxic carcinogen, DSS (5) induces colonic inflammation in rodents with clinical and histopathological similarity to human UC. (6) However, the colitis model using DSS needs a long period or cycle administration of DSS to induce colitis and colitis-related CRC, and the incidence and/or multiplicity of induced tumors are relatively low.…”

mentioning

confidence: 99%

β‐Catenin mutations in a mouse model of inflammation‐related colon carcinogenesis induced by 1,2‐dimethylhydrazine and dextran sodium sulfate

et al. 2005

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In a previous study, we developed a novel mouse model for colitisrelated carcinogenesis, utilizing a single dose of azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in drinking water. In the present study, we investigated whether colonic neoplasms can be developed in mice initiated with a single injection of another genotoxic colonic carcinogen 1,2-dimethylhydrazine (DMH), instead of AOM and followed by exposure of DSS in drinking water. Male crj: CD-1 (ICR) mice were given a single intraperitoneal administration (10, 20 or 40 mg/kg body weight) of DMH and 1-week oral exposure (2% in drinking water) of a non-genotoxic carcinogen, DSS. All animals were killed at week 20, histological alterations and immunohistochemical expression of β β β β-catenin, cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) were examined in induced colonic epithelial lesions (colonic dysplasias and neoplasms). Also, the β β β β-catenin gene mutations in paraffin-embedded colonic adenocarcinomas were analyzed by the single strand conformation polymorphism method, restriction enzyme fragment length polymorphism and direct sequencing. The incidences of colonic neoplasms with dysplastic lesions developed were 100% with 2.29 ± ± ± ± 0.95 multiplicity, and 100% with 10.38 ± ± ± ± 4.00 multiplicity in mice given DMH at doses of 10 mg/kg or 20 mg/kg and 2%DSS, respectively. Although approximately half of the mice given DMH at a dose of 40 mg/kg bodyweight were dead after 2-3 days after the injection, mice who received DMH 40 mg/kg and 2%DSS had 100% incidence of colonic neoplasms with 9.75 ± ± ± ± 6.29 multiplicity. Immunohistochemical investigation revealed that adnocarcinomas, induced by DMH at all doses and 2%DSS, showed positive reactivities against β β β β-catenin, COX-2 and iNOS. In DMH/ DSS-induced adenocarcinomas, 10 of 11 (90.9%) adenocacrcinomas had β β β β-catenin gene mutations. Half of the mutations were detected at codon 37 or 41, encoding serine and threonine that are direct targets for phosphorylation by glycogen synthase kinase-3β β β β. The present results suggests that, as in the previously reported model (AOM/DSS) our experimental protocol, DMH initiation followed by DSS, may provide a novel and useful mouse model for investigating inflammation-related colon carcinogenesis and for identifying xenobiotics with modifying effects. (Cancer Sci 2005; 96: 69-76) C olorectal cancer (CRC) is one of the most common nonsmoking related cancers. The risk for CRC is associated with extent and duration of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease.(1,2) The etiopathogenesis of IBD remains uncertain, although it is generally assumed that chronic inflammation is the primary driving force.(3) To understand the pathogenesis of IBD and IBD-related CRC, several animal models were reported. The chemically induced and genetic models of colonic inflammation do not completely mimic the disease situation found in UC patients, (4) although they are more readily available, reproduci...

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Absence of genotoxicity of the carcinogenic sulfated polysaccharides carrageenan and dextran sulfate in mammalian DNA repair and bacterial mutagenicity assays

Cited by 33 publications

References 11 publications

Effects of co-treatment of dextran sulfate sodium and MeIQx on genotoxicity and possible carcinogenicity in the colon of p53-deficient mice

Effects of co-treatment of dextran sulfate sodium and MeIQx on genotoxicity and possible carcinogenicity in the colon of p53-deficient mice

Development of an Inflammation-Associated Colorectal Cancer Model and Its Application for Research on Carcinogenesis and Chemoprevention

β‐Catenin mutations in a mouse model of inflammation‐related colon carcinogenesis induced by 1,2‐dimethylhydrazine and dextran sodium sulfate

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