title: Inhibition by resistant starch of red meat-induced promutagenic adducts in mouse colon.
abstract: Population studies have shown that high red meat intake may increase colorectal cancer risk. Our aim was to examine the effect of different amounts and sources of dietary protein on induction of the promutagenic adduct O(6)-methyl-2-deoxyguanosine (O(6)MeG) in colonocytes, to relate these to markers of large bowel protein fermentation and ascertain whether increasing colonic carbohydrate fermentation modified these effects. Mice (n = 72) were fed 15% or 30% protein as casein or red meat or 30% protein with 10% high amylose maize starch as the source of resistant starch. Genetic damage in distal colonocytes was detected by immunohistochemical staining for O(6)MeG and apoptosis. Feces were collected for measurement of pH, ammonia, phenols, p-cresol, and short-chain fatty acids (SCFA). O(6)MeG and fecal p-cresol concentrations were significantly higher with red meat than with casein (P < 0.018), with adducts accumulating in cells at the crypt apex. DNA adducts (P < 0.01) and apoptosis (P < 0.001) were lower and protein fermentation products (fecal ammonia, P < 0.05; phenol, P < 0.0001) higher in mice fed resistant starch. Fecal SCFA levels were also higher in mice fed resistant starch (P < 0.0001). This is the first demonstration that high protein diets increase promutagenic adducts (O(6)MeG) in the colon and dietary protein type seems to be the critical factor. The delivery of fermentable carbohydrate to the colon (as resistant starch) seems to switch from fermentation of protein to that of carbohydrate and a reduction in adduct formation, supporting previous observations that dietary resistant starch opposes the mutagenic effects of dietary red meat.
authors: Flinders Centre for Cancer Prevention and Control, Flinders University of South Australia, Bedford Park.
authors: Jean
authors: J
authors: Winter
authors: Laura
authors: L
authors: Nyskohus
authors: Graeme P
authors: GP
authors: Young
authors: Ying
authors: Y
authors: Hu
authors: Michael A
authors: MA
authors: Conlon
authors: Anthony R
authors: AR
authors: Bird
authors: David L
authors: DL
authors: Topping
authors: Richard K
authors: RK
authors: Le Leu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000187:drug effects*; D018736:DNA Adducts / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000633:toxicity; D004040:Dietary Carbohydrates / Q000494:pharmacology; D004044:Dietary Proteins / Q000494:pharmacology; D005243:Feces / Q000737:chemistry; D005285:Fermentation; D007420:Intestine, Large / Q000187:drug effects; D008297:Male; D008460:Meat / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000633:toxicity*; D013213:Starch / Q000494:pharmacology*
chemical_list: D018736:DNA Adducts; D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D009153:Mutagens; D013213:Starch; C015558:O(6)-methyl-2'-deoxyguanosine; D003849:Deoxyguanosine