Carcinogenesis, Vol. 24, No. 3, 595-603,
March 2003
© 2003 Oxford University Press
CARCINOGENESIS |
N-Nitroso compounds in the gastrointestinal tract of rats and in the feces of mice with induced colitis or fed hot dogs or beef
1 Eppley Institute for Research in Cancer and
2 Departments of Pharmaceutical Sciences and of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA and
3 Division of Population Studies, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
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.
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