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

Toden S, Lockett TJ, Topping DL, Scherer BL, Watson EJ, Southwood JG, Clarke JM - Cancer Biol. Ther. (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: a Preventative Health National Research Flagship ; Adelaide , Australia.

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.

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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 ).
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f0002: 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 ).

Mentions: Distal colonic AI increased with level of dietary HAMSB inclusion (Fig. 2A). The AI of the HAMSB40 fed rats was over twice that in the HAMSB0-fed rats (P < 0.001) and correlated positively with hepatic portal acetate and butyrate concentration (r = 0.49, P < 0.0001 and r = 0.65, P < 0.0001 respectively) but not propionate.Figure 2.


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

Toden S, Lockett TJ, Topping DL, Scherer BL, Watson EJ, Southwood JG, Clarke JM - Cancer Biol. Ther. (2014)

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 ).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4622003&req=5

f0002: 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 ).
Mentions: Distal colonic AI increased with level of dietary HAMSB inclusion (Fig. 2A). The AI of the HAMSB40 fed rats was over twice that in the HAMSB0-fed rats (P < 0.001) and correlated positively with hepatic portal acetate and butyrate concentration (r = 0.49, P < 0.0001 and r = 0.65, P < 0.0001 respectively) but not propionate.Figure 2.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: a Preventative Health National Research Flagship ; Adelaide , Australia.

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.

Show MeSH
Related in: MedlinePlus