A22
Effect of processed and red meat on endogenous nitrosation and DNA damage
Annemiek M.C.P. Joosen1, Gunter G.C. Kuhnle1, Timothy M. Barrow1, Amaia Azqueta Oscoz2, Sheila A. Bingham1
1MRC Dunn Human Nutrition Unit, Cambridge, UK, 2University of Oslo, Oslo, Norway
Haem in red meat (RM) stimulates the endogenous production of mutagenic nitrosocompounds (NOCs). Processed meat (PM) additionally contains high concentrations of preformed NOCs. We investigated whether preformed NOCs increase colorectal cancer risk by stimulating nitrosation and DNA damage.
Healthy volunteers were fed 366-420g PM (n=11) or RM (n=11) and a vegetarian (VEG) control diet for two weeks each. Faecal homogenates were analysed for haem and NOCs (as apparent total N-nitrosocompounds, ATNC) and associated supernatants for DNA-damaging capacity (Comet assay).
Faecal haem concentrations were significantly lower on the PM compared to the RM diet (PM 406±40 pmol/mg, RM 976±157 pmol/mg; P<0.01).
Faecal nitrosothiols and nitrosyl haem were not different, but other NOCs were higher on the PM than the RM diet (P<0.05). Nitrate levels were similar with the RM and VEG diets, but increased significantly on the PM diet with a significant correlation between nitrate and ATNC (Spearman’s rho 0.76, P<0.01).
Interestingly, DNA damage (arbitrary units, n=8) was lower, but not significantly, on the PM compared to the VEG diet (PM 176±23, VEG 216±19), as were EndoIII (PM 23±5, VEG 30±3) and FPG (PM 30±10, VEG 55±10) sensitive sites which recognise oxidised pyrimidines and 8-oxoguanine/ring-opened purines respectively.
Higher faecal NOC levels with PM consumption are likely caused by high nitrate levels in PM and support the link between high meat consumption and colorectal cancer. The similarity in genotoxicitiy of faecal waters from PM and VEG diets suggests the role of NOC in carcinogenesis is modulated by additional factors.
