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. 2014;15(11):1515-23.
doi: 10.4161/15384047.2014.955764.

Butyrylated starch affects colorectal cancer markers beneficially and dose-dependently in genotoxin-treated rats

Shusuke Toden  1 , Trevor J Lockett, David L Topping, Benjamin L Scherer, Emma-Jane L Watson, Jessica G Southwood, Julie M Clarke
Affiliations

Butyrylated starch affects colorectal cancer markers beneficially and dose-dependently in genotoxin-treated rats

Shusuke Toden et al. Cancer Biol Ther. 2014.

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: 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.

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Figures

Figure 1.
Figure 1.
Short chain fatty acid levels in (A) hepatic portal vein plasma concentrations (μmol/L) (B) cecal pools (μmoles) (C) cecal concentrations (μmol/L) (D) faecal pools (μmoles). Columns within a graph not sharing the same letter are significantly different P< 0.05, mean±SEM , n = 15/group).
Figure 2.
Figure 2.
Analysis of the distal colon of rats fed HAMSB and killed 6 hours after AOM injection. (A) AI as measured by morphological assessment of haematoxylin stained slides (n = 15/group) (B) Epithelial proliferation as measured by Ki67 immunohistochemistry (n = 15/group) (C) Genetic damage as measured by single-cell gel electrophoresis (comet) assay (n = 10/group). Columns within a graph not sharing the same letter are significantly different (P < 0.05, mean±SEM ).
Figure 3.
Figure 3.
Crypt cell position of AOM-induced apoptosis measured by morphological assessment of distal colonic epithelium in distal colon of rats fed HAMSB. Data are mean±SEM (n = 15). a,b,cHAMSB0 different to HAMSB10, HAMSB20 and HAMSB40 respectively (P<0 .05).
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