Journal Article

Strain differences in the susceptibility to azoxymethane and dextran sodium sulfate-induced colon carcinogenesis in mice

Rikako Suzuki, Hiroyuki Kohno, Shigeyuki Sugie, Hitoshi Nakagama and Takuji Tanaka

in Carcinogenesis

Volume 27, issue 1, pages 162-169
Published in print January 2005 | ISSN: 0143-3334
Published online August 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi205
Strain differences in the susceptibility to azoxymethane and dextran sodium sulfate-induced colon carcinogenesis in mice

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We have recently developed a mouse model for colitis-related colon carcinogenesis by a combined treatment with azoxymethane (AOM) and dextran sodium sulfate (DSS) in male ICR mice. However, strain differences in the sensitivity to AOM/DSS-induced colon carcinogenesis in mice have yet to be elucidated. The aim of this study was to determine the presence of any genetically determined differences in sensitivity to our model of colon carcinogenesis in four inbred strains of mice. Male Balb/c, C3H/HeN, C57BL/6N and DBA/2N mice were given a single intraperitoneal injection of AOM (10 mg/kg body wt), followed by 1% DSS (w/v) in drinking water for 4 days, and thereafter they received no further treatment for up to 16 weeks. At the end of the study (Week 18), all mice were killed and a histopathological analysis of their colon was performed. The incidence of colonic adenocarcinoma was 100% with a multiplicity (no. of tumors/mouse) of 7.7 ± 4.3 in the Balb/c mice and 50% with a multiplicity of 1.0 ± 1.2 in the C57BL/6N mice. On the other hand, only a few colonic adenomas, but no adenocarcinomas, developed in the C3H/HeN mice (29% incidence with a multiplicity of 0.7 ± 1.5) and the DBA/2N mice (20% incidence with a multiplicity of 0.2 ± 0.4). The inflammation and immunohistochemical nitrotyrosine-positivity scores of the mice treated with AOM and DSS in the decreasing order were as follows: C3H/HeN > Balb/c > DBA/2N > C57BL/6N and Balb/c > C57BL/6N > C3H/HeN > DBA/2N, respectively. Our results thus indicated the presence of strain differences in the susceptibility to AOM/DSS-induced colonic tumorigenesis. These differences may have been directly influenced by the response to nitrosation stress due to the inflammation caused by DSS.

Keywords: AOM, azoxymethane; CRC, colorectal cancer; CYP, Cytochrome P450; DSS, dextran sodium sulfate; IBD, inflammatory bowel disease; IKK, IκB kinase; LPS, lipopolysaccharide; UC, ulcerative colitis

Journal Article.  4969 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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