title: O⁶-carboxymethylguanine DNA adduct formation and lipid peroxidation upon in vitro gastrointestinal digestion of haem-rich meat.
abstract: METHODS
  Epidemiological and clinical studies have demonstrated that the consumption of red haem-rich meat may contribute to the risk of colorectal cancer. Two hypotheses have been put forward to explain this causal relationship, i.e. N-nitroso compound (NOC) formation and lipid peroxidation (LPO).
  
  
  RESULTS
  In this study, the NOC-derived DNA adduct O(6)-carboxymethylguanine (O(6)-CMG) and the LPO product malondialdehyde (MDA) were measured in individual in vitro gastrointestinal digestions of meat types varying in haem content (beef, pork, chicken). While MDA formation peaked during the in vitro small intestinal digestion, alkylation and concomitant DNA adduct formation was observed in seven (out of 15) individual colonic digestions using separate faecal inocula. From those, two haem-rich meat digestions demonstrated a significantly higher O(6)-CMG formation (p < 0.05). MDA concentrations proved to be positively correlated (p < 0.0004) with haem content of digested meat. The addition of myoglobin, a haem-containing protein, to the digestive simulation showed a dose-response association with O(6)-CMG (p = 0.004) and MDA (p = 0.008) formation.
  
  
  CONCLUSIONS
  The results suggest the haem-iron involvement for both the LPO and NOC pathway during meat digestion. Moreover, results unambiguously demonstrate that DNA adduct formation is very prone to inter-individual variation, suggesting a person-dependent susceptibility to colorectal cancer development following haem-rich meat consumption.
authors.affiliation: Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Vanden Bussche
authors.forename: Lieselot Y
authors.initials: LY
authors.lastname: Hemeryck
authors.forename: Thomas
authors.initials: T
authors.lastname: Van Hecke
authors.forename: Gunter G C
authors.initials: GG
authors.lastname: Kuhnle
authors.forename: Frank
authors.initials: F
authors.lastname: Pasmans
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Moore
authors.forename: Tom
authors.initials: T
authors.lastname: Van de Wiele
authors.forename: Stefaan
authors.initials: S
authors.lastname: De Smet
authors.forename: Lynn
authors.initials: L
authors.lastname: Vanhaecke
mesh_terms: D000328:Adult; D000818:Animals; D018938:Caco-2 Cells; D002645:Chickens; D018736:DNA Adducts / Q000032:analysis / Q000378:metabolism*; D004063:Digestion; D005243:Feces / Q000382:microbiology; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D008460:Meat / Q000032:analysis; D008875:Middle Aged; D009603:Nitroso Compounds / Q000032:analysis* / Q000378:metabolism; D013552:Swine
chemical_list: D018736:DNA Adducts; D009603:Nitroso Compounds; C121409:O(6)-carboxymethyguanine; D006418:Heme; D008315:Malondialdehyde; D006147:Guanine
keywords: In vitro gastrointestinal digestion; Malondialdehyde; Meat consumption; N-nitroso compounds; O6-carboxymethylguanine