Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation

• Published in: Carcinogenesis (New York) Vol. 22; no. 1; pp. 199 - 202
• Main Authors: Hughes, R., Cross, A.J., Pollock, J.R.A., Bingham, S.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.01.2001; Oxford Publishing Limited (England)
• Subjects: Adult; Animals; apparent total N-nitroso compounds; ATNC; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Cattle; Colon - metabolism; Cross-Over Studies; Diet; Feces; Foods and miscellaneous; Humans; Male; mean transit time; Meat - adverse effects; Medical sciences; Middle Aged; MTT; N-nitroso compounds; Nitrites - metabolism; Nitrogen - urine; nitrosation; Nitroso Compounds - adverse effects; Nitroso Compounds - metabolism; NOC; p-aminobenzoic acid; PABA; Swine; Tumors; Human; Nitroso compound; Nitrites; Oral administration; Supplemented diet; Malignant tumor; Nitrosation; Carcinogenesis; Dose activity relation; Digestive transit; Meat; Increasing dose; Endogenous; Risk factor; Colon; Feces; Mechanism of action
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/22.1.199

Human male volunteers were studied in a metabolic facility whilst they were fed randomized controlled diets. In eight volunteers there was a significant increase in faecal apparent total N-nitroso compounds (ATNC) and nitrite excretion (P < 0.0001 and P = 0.046, respectively) when randomized doses of meat were increased from 0 to 60, 240 and 420 g/day over 10 day periods. Mean (± SE) faecal ATNC levels were 54 ± 7 μg/day when the diets contained no meat, 52 ± 11 μg/day when the diets contained 60 g meat/day, 159 ± 33 μg/day with 240 g meat and 199 ± 36 μg/day with 420 g meat. Higher concentrations of NOC were associated with longer times of transit in the gut (r = 0.55, P = 0.001) and low faecal weight (r = –0.51, P = 0.004). There was no significant decline in levels in individuals fed 420 g meat for 40 days. The exposures found on the higher meat diets were comparable with other sources of N-nitroso compounds (NOC), such as tobacco smoke. Many NOC are known large bowel initiators and promotors in colon cancer, inducing G→A transitions in codons 12 and 13 of K-ras. Endogenous NOC formation, combined with prolonged transit times in the gut, may explain the epidemiological associations between high meat/low fibre diets and colorectal cancer risk.