title: Role of Red Meat and Resistant Starch in Promutagenic Adduct Formation, MGMT Repair, Thymic Lymphoma and Intestinal Tumourigenesis in Msh2 -Deficient Mice.
abstract: Red meat may increase promutagenic lesions in the colon. Resistant starch (RS) can reduce these lesions and chemically induced colon tumours in rodents. Msh2 is a mismatch repair (MMR) protein, recognising unrepaired promutagenic adducts for removal. We determined if red meat and/or RS modulated DNA adducts or oncogenesis in Msh2-deficient mice. A total of 100 Msh2-/- and 60 wild-type mice consumed 1 of 4 diets for 6 months: control, RS, red meat and red meat+RS. Survival time, aberrant crypt foci (ACF), colon and small intestinal tumours, lymphoma, colonic O6-methyl-2-deoxyguanosine (O6MeG) adducts, methylguanine methyltransferase (MGMT) and cell proliferation were examined. In Msh2-/- mice, red meat enhanced survival compared to control (p<0.01) and lowered total tumour burden compared to RS (p<0.167). Msh2-/- mice had more ACF than wild-type mice (p<0.014), but no colon tumours developed. Msh2-/- increased cell proliferation (p<0.001), lowered DNA O6MeG adducts (p<0.143) and enhanced MGMT protein levels (p<0.001) compared to wild-type mice, with RS supplementation also protecting against DNA adducts (p<0.01). No link between red meat-induced promutagenic adducts and risk for colorectal cancer was observed after 6 months' feeding. Colonic epithelial changes after red meat and RS consumption with MMR deficiency will differ from normal epithelial cells.
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, S.A., Australia.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Winter
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Young
authors.forename: Maija R J
authors.initials: MR
authors.lastname: Kohonen-Corish
authors.forename: Richard K
authors.initials: RK
authors.lastname: Le Leu
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage; D018736:DNA Adducts / Q000096:biosynthesis*; D053843:DNA Mismatch Repair; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D005260:Female; D007414:Intestinal Neoplasms / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D008223:Lymphoma / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051718:MutS Homolog 2 Protein / Q000172:deficiency* / Q000235:genetics; D009153:Mutagens / Q000378:metabolism; D054647:Nutrigenomics; D000069466:Red Meat / Q000009:adverse effects; D012307:Risk Factors; D013213:Starch / Q000008:administration & dosage*; D013953:Thymus Neoplasms / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D018736:DNA Adducts; D009153:Mutagens; D025521:Tumor Suppressor Proteins; D013213:Starch; D015254:DNA Modification Methylases; C528331:MGMT protein, mouse; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes