New marker of colon cancer risk associated with heme intake: 1,4-dihydroxynonane mercapturic acid.
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.
Pierre
Fabrice
F
Ecole Nationale Vétérinaire Toulouse, UMR INRA-ENVT 1089 Xénobiotiques, Toulouse, France.
Peiro
Géraldine
G
Taché
Sylviane
S
Cross
Amanda J
AJ
Bingham
Sheila A
SA
Gasc
Nicole
N
Gottardi
Gaëlle
G
Corpet
Denis E
DE
Guéraud
Françoise
F
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
C501116:1,4-dihydroxynonene mercapturic acid; D014408:Biomarkers, Tumor; D006418:Heme; D007501:Iron; D000111:Acetylcysteine