title: Accumulation of promutagenic DNA adducts in the mouse distal colon after consumption of heme does not induce colonic neoplasms in the western diet model of spontaneous colorectal cancer.
abstract: METHODS
  Red meat is considered a risk factor for colorectal cancer (CRC). Heme is considered to promote colonic hyperproliferation and cell damage. Resistant starch (RS) is a food that ferments in the colon with studies demonstrating protective effects against CRC. By utilizing the western diet model of spontaneous CRC, we determined if feeding heme (as hemin chloride) equivalent to a high red meat diet would increase colonic DNA adducts and CRC and whether RS could abrogate such effects.
  
  
  RESULTS
  Four groups of mice: control, heme, RS and heme + RS were fed diets for 1 or 18 months. Colons were analyzed for apoptosis, proliferation, DNA adducts "8-hydroxy-2-deoxyguanosine" and "O(6) -methyl-2-deoxyguanosine" (O(6) MeG), and neoplasms. In the short term, heme increased cell proliferation (p < 0.05). Changes from 1 to 18 months showed increased cell proliferation (p < 0.01) and 8-hydroxy-2-deoxyguanosine adducts (p < 0.05) in all groups, but only heme-fed mice showed reduced apoptosis (p < 0.01) and increased O(6) MeG adducts (p < 0.01). The incidence of colon neoplasms was not different between any interventions.
  
  
  CONCLUSIONS
  We identified heme to increase proliferation in the short term, inhibit apoptosis over the long term, and increase O(6) MeG adducts in the colon over time although these changes did not affect colonic neoplasms within this mouse model.
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, South Australia, Australia.
authors.forename: Jean
authors.initials: J
authors.lastname: Winter
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Young
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Silvia W
authors.initials: SW
authors.lastname: Gratz
authors.forename: Michael A
authors.initials: MA
authors.lastname: Conlon
authors.forename: Richard K
authors.initials: RK
authors.lastname: Le Leu
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003110:Colonic Neoplasms / Q000209:etiology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology; D018736:DNA Adducts / Q000378:metabolism*; D066273:Diet, Western / Q000009:adverse effects*; D005243:Feces; D006418:Heme / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000378:metabolism; D013213:Starch / Q000494:pharmacology
chemical_list: D018736:DNA Adducts; D009153:Mutagens; D006418:Heme; D013213:Starch
keywords: 8-Hydroxy-2-deoxyguanosine; Heme; O6-Methyl-2-deoxyguanosine; Red meat; Resistant starch