Journal Article

<i>N</i>-Nitroso compounds in the gastrointestinal tract of rats and in the feces of mice with induced colitis or fed hot dogs or beef

Sidney S. Mirvish, James Haorah, Lin Zhou, Melissa Hartman, Chantey R. Morris and Marge L. Clapper

in Carcinogenesis

Volume 24, issue 3, pages 595-603
Published in print March 2003 | ISSN: 0143-3334
Published online March 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/24.3.595
N-Nitroso compounds in the gastrointestinal tract of rats and in the feces of mice with induced colitis or fed hot dogs or beef

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Because colonic N-nitroso compounds (NOC) may be a cause of colon cancer, we determined total NOC levels by Walters’ method in the gastrointestinal tract and feces of rodents: (i) feces of C57BL mice fed chow and semi-purified diets contained 3.2 ± 0.4 and 0.46 ± 0.06 NOC/g, respectively (P < 0.01, mean ± SD). (ii) NOC levels for gastrointestinal contents of three groups of Sprague–Dawley rats fed chow diet were 0.9 ± 0.05 (diet), 0.2 ± 0 (stomach), 0.3–0.4 (small intestine), 0.7–1.6 (cecum and colon) and 2.6 ± 0.6 (feces) nmol/g. NOC precursor (NOCP) levels (measured as NOC after mild nitrosation) for two rat groups fed chow diet showed a 16-fold increase from stomach to proximal small intestine (mean, 6.2 μmol/g), and a 1.7-fold increase from distal colon to feces (mean, 11.6 μmol/g). (iii) Eight Min and five C57BL/6J mice received 4% dextran sulfate sodium in drinking water on days 1–4 to induce acute colitis. This increased fecal NOC levels 1.9-fold on day 5 in both strains (P ≤ 0.04), probably due to NO synthase-derived nitrosating agents in the colon. (iv) Following studies on humans fed beef [Hughes et al. (2001) Carcinogenesis, 22, 199], Swiss mice received semi-purified diets mixed with 18% of beef plus pork hot dogs or sautéed beef for 7 days. On day 7, individual 24-h fecal NOC outputs were determined. In three hot dog and two beef groups with 5 mice/group, mean fecal NOC output/day was 3.7–5.0 (hot dog) and 2.0–2.9 (beef) times that for control groups fed semi-purified diet alone (P < 0.002 for each of combined groups). These groups showed little change in fecal NOCP output. (v) Initial purification of rat fecal NOCP by adsorption–desorption and HPLC is described. Results should help evaluate the view that colonic NOC causes colon cancer associated with colitis and ingestion of red and nitrite-preserved meat.

Keywords: DSS, dextran sulfate sodium; Exp., Experiment; GIT, gastrointestinal tract; iNOS, inducible nitric oxide synthase; NO, nitric oxide; NOC, N-nitroso compounds; NOCP, NOC precursors; SP, semi-purified

Journal Article.  8930 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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