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Carcinogenesis Advance Access originally published online on August 13, 2008
Carcinogenesis 2008 29(11):2190-2194; doi:10.1093/carcin/bgn192
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
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Effects of high-amylose maize starch and butyrylated high-amylose maize starch on azoxymethane-induced intestinal cancer in rats

Julie M. Clarke1,2,*, David L. Topping1,2, Anthony R. Bird1,2, Graeme P. Young1,3 and Lynne Cobiac4

1 Preventative Health National Research Flagship
2 CSIRO Human Nutrition, Adelaide, South Australia
3 Flinders Cancer Control Alliance, Flinders University, Bedford Park, South Australia
4 Department of Nutrition and Dietetics, School of Medicine, Flinders University, Bedford Park, South Australia

* To whom correspondence should be addressed. CSIRO Human Nutrition, PO Box 10041, Adelaide BC 5000, South Australia. Tel: +61 8 8303 8800; Fax: +61 8 8303 8899.Email: julie.clarke{at}csiro.au

Colorectal cancer (CRC) is a major cause of death worldwide. Studies suggest that dietary fibre offers protection perhaps by increasing colonic fermentative production of butyrate. This study examined the importance of butyrate by investigating the effects of resistant starch (RS) and butyrylated-RS on azoxymethane (AOM)-induced CRC in rats. Four groups (n = 30 per group) of Sprague–Dawley rats were fed AIN-93G-based diets containing a standard low-RS maize starch (LAMS), LAMS + 3% tributyrin (LAMST), 10% high-amylose maize starch (HAMS) and 10% butyrylated HAMS (HAMSB) for 4 weeks. Rats were injected once weekly for 2 weeks with 15 mg/kg AOM, maintained on diets for 25 weeks and then killed. Butyrate concentrations in large bowel digesta were higher in rats fed HAMSB than other groups (P < 0.001); levels were similar in HAMS, LAMS and LAMST groups. The proportion of rats developing tumours were lower in HAMS and HAMSB than LAMS (P < 0.05), and the number of tumours per rat were lower in HAMSB than LAMS (P < 0.05). Caecal digesta butyrate pools and concentrations were negatively correlated with tumour size (P < 0.05). Hepatic portal plasma butyrate concentrations were higher (P < 0.001) in the HAMSB compared with other groups and negatively correlated with tumour number per rat (P < 0.009) and total tumour size for each rat (P = 0.05). HAMSB results in higher luminal butyrate than RS alone or tributyrin. This is associated with reduced tumour incidence, number and size in this rat model of CRC supporting the important protective role of butyrate. Interventional strategies designed to maximize luminal butyrate may be of protective benefit in humans.

Abbreviations: AOM, azoxymethane; CRC, colorectal cancer; CSIRO, Commonwealth Scientific and Industrial Research Organisation; HAMS, high-amylose maize starch; HAMSB, butyrylated high-amylose maize starch; LAMS, low-amylose maize starch; RS, resistant starch; SCFA, short chain fatty acids

Received March 19, 2008; revised July 13, 2008; accepted August 1, 2008.


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