Dose-dependent promoting effect of dextran sodium sulfate on mouse colon carcinogenesis initiated with azoxymethane.
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.
Suzuki
R
R
Department of Oncologic Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. rikako@kanazawa-med.ac.jp.
Kohno
H
H
Sugie
S
S
Tanaka
T
T
D000818:Animals; D001397:Azoxymethane / Q000008:administration & dosage / Q000633:toxicity; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D003043:Cocarcinogenesis; D003092:Colitis / Q000139:chemically induced / Q000473:pathology; D003108:Colonic Diseases / Q000139:chemically induced / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014456:Ulcer / Q000139:chemically induced / Q000473:pathology
D002273:Carcinogens; C002744:3-nitrotyrosine; D014443:Tyrosine; D016264:Dextran Sulfate; D001397:Azoxymethane