title: Effect of processed and red meat on endogenous nitrosation and DNA damage.
abstract: Haem in red meat (RM) stimulates the endogenous production of mutagenic nitroso compounds (NOC). Processed (nitrite-preserved red) meat additionally contains high concentrations of preformed NOC. In two studies, of a fresh RM versus a vegetarian (VEG) diet (six males and six females) and of a nitrite-preserved red meat (PM) versus a VEG diet (5 males and 11 females), we investigated whether processing of meat might increase colorectal cancer risk by stimulating nitrosation and DNA damage. Meat diets contained 420 g (males) or 366 g (females) meat/per day. Faecal homogenates from day 10 onwards were analysed for haem and NOC and associated supernatants for genotoxicity. Means are adjusted for differences in male to female ratios between studies. Faecal NOC concentrations on VEG diets were low (2.6 and 3.5 mmol/g) but significantly higher on meat diets (PM 175 +/- 19 nmol/g versus RM 185 +/- 22 nmol/g; P = 0.75). The RM diet resulted in a larger proportion of nitrosyl iron (RM 78% versus PM 54%; P < 0.0001) and less nitrosothiols (RM 12% versus PM 19%; P < 0.01) and other NOC (RM 10% versus PM 27%; P < 0.0001). There was no statistically significant difference in DNA breaks induced by faecal water (FW) following PM and RM diets (P = 0.80). However, PM resulted in higher levels of oxidized pyrimidines (P < 0.05). Surprisingly, VEG diets resulted in significantly more FW-induced DNA strand breaks than the meat diets (P < 0.05), which needs to be clarified in further studies. Meats cured with nitrite have the same effect as fresh RM on endogenous nitrosation but show increased FW-induced oxidative DNA damage.
authors.affiliation: MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Annemiek M C P
authors.initials: AM
authors.lastname: Joosen
authors.forename: Gunter G C
authors.initials: GG
authors.lastname: Kuhnle
authors.forename: Sue M
authors.initials: SM
authors.lastname: Aspinall
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Barrow
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lecommandeur
authors.forename: Amaya
authors.initials: A
authors.lastname: Azqueta
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Collins
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Bingham
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020552:Comet Assay; D018592:Cross-Over Studies; D004249:DNA Damage; D014676:Diet, Vegetarian; D005243:Feces / Q000737:chemistry; D005260:Female; D006418:Heme / Q000378:metabolism; D006801:Humans; D008297:Male; D008460:Meat / Q000009:adverse effects*; D008875:Middle Aged; D009153:Mutagens; D015538:Nitrosation; D009603:Nitroso Compounds / Q000378:metabolism*; D055815:Young Adult
chemical_list: D009153:Mutagens; D009603:Nitroso Compounds; D006418:Heme