Diet-induced endogenous formation of nitroso compounds in the GI tract.

TitleDiet-induced endogenous formation of nitroso compounds in the GI tract.
Publication TypeJournal Article
Year of Publication2007
AuthorsKuhnle, GGC, Story, GW, Reda, T, Mani, AR, Moore, KP, Lunn, JC, Bingham, SA
JournalFree Radic Biol Med
Volume43
Issue7
Pagination1040-7
Date Published2007 Oct 01
ISSN0891-5849
KeywordsApoproteins, Diet, Diet, Vegetarian, Electron Spin Resonance Spectroscopy, Feces, Gastric Mucosa, Gastrointestinal Tract, Heme, Hemoglobins, Humans, Ileum, Iron, Kinetics, Meat, Nitroso Compounds, S-Nitrosothiols, Serum Albumin, Bovine
Abstract

Red or processed meat, but not white meat or fish, is associated with colorectal cancer. The endogenous formation of nitroso compounds is a possible explanation, as red or processed meat--but not white meat or fish--causes a dose-dependent increase in fecal apparent total N-nitroso compounds (ATNC) and the formation of nitroso-compound-specific DNA adducts. Red meat is particularly rich in heme and heme has also been found to promote the formation of ATNC. To investigate the underlying mechanism of ATNC formation, fecal and ileal samples of volunteers fed a high red meat or a vegetarian diet were analyzed for nitrosyl iron, nitrosothiols, and heme. To simulate the processes in the stomach, food homogenates and hemoglobin were incubated under simulated gastric conditions. Nitrosyl iron and nitrosothiols were significantly (p < 0.0001) increased in ileal and fecal samples after a high red meat diet compared with a vegetarian diet; significantly more nitrosyl iron than nitrosothiols was detectable in ileal (p < 0.0001) and fecal (p < 0.001) samples. The strong correlation between fecal nitrosyl iron and heme (0.776; p < 0.0001) suggested that nitrosyl heme is the main source of nitrosyl iron, and ESR confirmed the presence of nitrosyl heme in fecal samples after a high red meat diet. Under simulated gastric conditions, mainly nitrosothiols were formed, suggesting that acid-catalyzed thionitrosation is the initial step in the endogenous formation of nitroso compounds. Nitrosyl heme and other nitroso compounds can then form under the alkaline and reductive conditions of the small and large bowel.

DOI10.1016/j.freeradbiomed.2007.03.011
Alternate JournalFree Radic. Biol. Med.
Citation Key10.1016/j.freeradbiomed.2007.03.011
PubMed ID17761300
Grant ListMC_U105630924 / / Medical Research Council / United Kingdom