Effect of feeding nitrite, ascorbate, hemin, and omeprazole on excretion of fecal total apparent N-nitroso compounds in mice.
It was proposed that colon cancer induced by red and nitrite-preserved meat is due to meat-derived N-nitroso compounds in the colonic contents. To explore this view, we previously showed that feeding beef and hot dogs increased the fecal output of total apparent N-nitroso compounds (ANC) in mice. In the current project, adult Swiss mice were fed a semipurified diet and water containing additives for 7 days. Feces from individual mice was collected on day 7, dried, and extracted with water. Extracts were analyzed for ANC as before. Feeding 2.0 g sodium nitrite (NaNO2)/L drinking water raised fecal ANC levels from 5 to 63 nmol/g feces. In a dose-response study, fecal ANC levels were proportional to the nitrite concentration squared. Even 32 mg NaNO2/L raised fecal ANC levels 2.3-fold (P < 0.05). In other results, 64, 125, and 250 mg hemin/kg diet, fed with 2 g NaNO2/L water, showed 2.3, 2.2, and 4.6 times the ANC level for nitrite alone. Sodium nitrate (12 g/L water) did not affect fecal ANC output. Omeprazole (400 mg/kg diet) and sodium ascorbate (23 g/kg diet), when fed with 1 g NaNO2/L water, lowered fecal ANC levels by 65 and 41%, indicating that, when nitrite was fed, acid-catalyzed reactions in the stomach produced ANC, which passed down the gut to the feces. Tests indicated that nitrosothiols constituted about 20% of fecal and hot dog ANC. The observed effect of NaNO2 is thus far not consistent with the proposed hypothesis. The enhancement by hemin may help explain why red meat is a cause of colon cancer.
Mirvish
Sidney S
SS
Eppley Institute for Research in Cancer, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA. smirvish@unmc.edu
Davis
Michael E
ME
Lisowyj
Michal P
MP
Gaikwad
Nilesh W
NW
D000821:Animal Feed; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005243:Feces / Q000737:chemistry; D006427:Hemin / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D008461:Meat Products; D051379:Mice; D009603:Nitroso Compounds / Q000032:analysis / Q000378:metabolism*; D009853:Omeprazole / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity
D009603:Nitroso Compounds; D006427:Hemin; D009853:Omeprazole; D012977:Sodium Nitrite; D001205:Ascorbic Acid