title: New marker of colon cancer risk associated with heme intake: 1,4-dihydroxynonane mercapturic acid.
abstract: BACKGROUND
  Red meat consumption is associated with an increased risk of colon cancer. Animal studies show that heme, found in red meat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8-iso-prostaglandin-F(2)alpha (8-iso-PGF(2)alpha), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake.
  
  
  METHODS
  We measured urinary excretion of 8-iso-PGF(2)alpha and 1,4-dihydroxynonane mercapturic acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat baseline diet, 120 g/d red meat, baseline diet supplemented with heme iron, and baseline diet supplemented with non-heme iron).
  
  
  RESULTS
  DHN-MA excretion increased dramatically in rats fed high heme diets, and the excretion paralleled the number of preneoplastic lesions in azoxymethane initiated rats (P < 0.0001). In the human study, the heme supplemented diet resulted in a 2-fold increase in DHN-MA (P < 0.001). Urinary 8-iso-PGF(2)alpha increased moderately in rats fed a high heme diet (P < 0.0001), but not in humans.
  
  
  CONCLUSIONS
  Urinary DHN-MA is a useful noninvasive biomarker for determining the risk of preneoplastic lesions associated with heme iron consumption and should be further investigated as a potential biomarker of colon cancer risk.
authors.affiliation: Ecole Nationale Vétérinaire Toulouse, UMR INRA-ENVT 1089 Xénobiotiques, Toulouse, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Pierre
authors.forename: Géraldine
authors.initials: G
authors.lastname: Peiro
authors.forename: Sylviane
authors.initials: S
authors.lastname: Taché
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Bingham
authors.forename: Nicole
authors.initials: N
authors.lastname: Gasc
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Gottardi
authors.forename: Denis E
authors.initials: DE
authors.lastname: Corpet
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéraud
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000821:Animal Feed; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D004032:Diet; D005260:Female; D006418:Heme / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344; D012306:Risk
chemical_list: C501116:1,4-dihydroxynonene mercapturic acid; D014408:Biomarkers, Tumor; D006418:Heme; D007501:Iron; D000111:Acetylcysteine