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.

Keywords:

• apoptosis
• azoxymethane
• butyrylated high amylose maize starch
• DNA damage
• resistant starch

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors would like to thank Mr Simon Windsor for his technical assistance, Dr Ian Saunders of CSIRO Mathematical and Information Sciences (Urrbrae, South Australia) for his statistical advice. In addition we would like to thank Ingredion Inc. (formerly National Starch Food Chemical Co; Bridgewater, New Jersey) for supplying the HAMSB.

Funding

This work was supported by the Commonwealth Scientific and Industrial Research Organization Preventative Health National Research Flagship (PO Box 10041, Adelaide BC, Adelaide, South Australia 5000).