Role of red meat and resistant starch in pro-mutagenic adduct formation, MGMT repair, thymic lymphoma and intestinal tumourigenesis in Msh2 deficient mice

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.