HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Dose-dependent promoting effect of dextran sodium sulfate on mouse colon carcinogenesis initiated with azoxymethane

R. Suzuki1,2, H. Kohno1, S. Sugie1 and T. Tanaka1

1Department of Oncologic Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan and 2Research Fellow of the Japan Society for the Promotion of Science, Chiyoda-ku, Tokyo, Japan

Offprint requests to: Dr. Rikako Suzuki, Department of Oncologic Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan. e-mail: rikako@kanazawa-med.ac.jp


Summary. We previously reported a powerful tumor-promoting ability of dextran sodium sulfate (DSS) in a novel mouse model for colitis-related colon carcinogenesis initiated with azoxymethane (AOM). To determine the dose-dependent influence of DSS in our animal model, male ICR mice were given a single intraperitoneal injection of AOM (10 mg/kg body weight), followed by DSS at dose levels of 2, 1, 0.5, 0.25, and 0.1% (w/v) in drinking water for 1 week. All animals were sacrificed at week 14 and histological alterations in their colon and nitrotyrosine immunohistochemistry were examined to evaluate the nitrosative stress. In the mice which received AOM and 2% DSS, the incidences (multiplicity) of colonic tubular adenoma and adenocarcinoma were 75% (1.25±1.26/mouse) and 100% (2.75±2.22/mouse), respectively. Mice given AOM and 1% DSS had 80% incidence of adenoma (1.00±0.71/mouse) and 60% incidence of adenocarcinoma (1.40±2.07/mouse) in the colon. In a mouse treated with AOM and 0.5% DSS, only one colonic adenoma (20% incidence with 0.20±0.45 multiplicity) developed. Higher frequency of high-grade colonic dysplasia was noted in mice given AOM and 2% or 1% DSS when compared with mice treated with AOM and lower doses of DSS. Also, scoring of inflammation and nitrotyrosine immunoreactivity suggested that severe inflammation and nitrosation stress caused by high-doses (2% and 1%) of DSS contribute its tumor-promoting effects in mouse colon carcinogenesis initiated with a low dose of AOM. Thus, our findings indicate that a tumor-promoting effect of DSS was dose-dependent (1% or more) and the effect might occur under the condition of inflammation and nitrosation stress. Histol Histopathol 20, 483-492 (2005).

Key words: Dose-dependency, Promotion, DSS, AOM, Mouse colon carcinogenesis

DOI: 10.14670/HH-20.483