title: Butyrylated starch affects colorectal cancer markers beneficially and dose-dependently in genotoxin-treated rats.
abstract: Population studies suggest that greater dietary fiber intake may lower colorectal cancer (CRC) risk, possibly through the colonic bacterial fermentative production of butyrate. Butyrylated starch delivers butyrate to the colon of humans with potential to reduce CRC risk but high doses may exacerbate risk through promoting epithelial proliferation. Here we report the effects of increasing dietary butyrylated high amylose maize starch (HAMSB) on azoxymethane (AOM) induced distal colonic DNA damage, cell proliferation, mucus layer thickness and apoptosis in rats. Five groups of 15 rats were fed AIN-93G based diets containing 0-40% HAMSB for 4 weeks then injected with (AOM) and killed 6 hours later. Large bowel total SCFA, acetate and butyrate pools and hepatic portal venous plasma total SCFA, acetate and butyrate concentrations were higher with greater HAMSB intake. Distal colonic epithelial apoptotic index and colonic mucus thickness increased, while DNA single strand breaks decreased dose-dependently with greater HAMSB intake. Colonocyte proliferation rates were unaffected by diet. These data suggest that increasing large bowel butyrate may reduce the risk of CRC in a dose dependent manner by enhancing apoptotic surveillance in the colonic epithelium for damaged cells without promoting the risk of tumorigenesis through increased cell proliferation.
authors.affiliation: a Preventative Health National Research Flagship ; Adelaide , Australia.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Toden
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Lockett
authors.forename: David L
authors.initials: DL
authors.lastname: Topping
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Scherer
authors.forename: Emma-Jane L
authors.initials: EJ
authors.lastname: Watson
authors.forename: Jessica G
authors.initials: JG
authors.lastname: Southwood
authors.forename: Julie M
authors.initials: JM
authors.lastname: Clarke
mesh_terms: D000641:Ammonia / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002087:Butyrates / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004249:DNA Damage; D004032:Diet; D004040:Dietary Carbohydrates; D005232:Fatty Acids, Volatile / Q000097:blood / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009093:Mucus / Q000378:metabolism; D009153:Mutagens / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D013213:Starch / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002087:Butyrates; D004040:Dietary Carbohydrates; D005232:Fatty Acids, Volatile; D009153:Mutagens; D000641:Ammonia; D013213:Starch
keywords: AI, apoptotic index; AOM, azoxymethane; Abbreviations:; DNA damage; HAMS, high amylose maize starch; HAMSB butyrylated high amylose maize starch; HAMSB0, base diet containing 0% HAMSB; HAMSB10, base diet containing 10% HAMSB; HAMSB20, base diet containing 20% HAMSB; HAMSB40, base diet containing 40% HAMSB; HAMSB5, base diet containing 5% HAMSB; RS, resistant starch; SCFA, short chain fatty acid; SSB, single-stranded DNA breaks; apoptosis; azoxymethane; butyrylated high amylose maize starch; resistant starch