Carcinogenesis, Vol. 20, No. 5, 805-810,
May 1999
© 1999 Oxford University Press
Intestinal tumorigenesis in the Apc1638N mouse treated with aspirin and resistant starch for up to 5 months
Department of Histopathology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP,
1 Department of Surgery, Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, B-1200 Brussels, Belgium,
2 Human Nutrition Research Centre, Department of Biological and Nutritional Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 7RU, UK,
3 MGC, Department of Human Genetics, Sylvius Laboratory, Faculty of Medicine, Wassenaareseweg 72, 2300 RA Leiden, The Netherlands and
4 Department of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4AA, UK
The Apc1638N mouse model, which carries a targeted mutant allele within the adenomatous polyposis (Apc) gene and develops intestinal tumours spontaneously, predominantly in the small bowel, was used to investigate the effects of two potential chemopreventive agents, aspirin and 
-amylase resistant starch (RS). Heterozygous Apc+/Apc1638N mice were fed semi-purified diets rich in animal fat, animal proteins and sucrose and low in dietary fibre (Western style diets) from ~6 weeks up to 6 months of age. Two of the diets contained aspirin (300 mg/kg diet) and two RS (1:1 mixture of raw potato starch: Hylon VII at 200 g/kg diet) in a 2x2 factorial design. A fifth treatment group were fed a conventional rodent chow diet. The mice fed the Western style diets became almost three times as fat as the chow-fed mice but this did not affect tumour yield. Treatment with RS resulted in significantly more intestinal tumours whereas aspirin alone had no effect. However, there was a significant aspirinxRS interaction, which suggests that aspirin could prevent the small intestine tumour-enhancing effects of RS in this Apc-driven tumorigenesis model. The possibility that large amounts of purified forms of resistant starch may have adverse effects within the small bowel is a novel observation that requires further investigation since greater intakes of starchy foods (and of RS) are being encouraged as a public health measure in compensation for reduced dietary fat intake. However, it remains possible that any increased risk is restricted to carriers of germline mutations in APC.
Abbreviations: Apc, mouse adenomatous polyposis coli gene; COX-2, cyclo-oxygenase-2; FAP, familial adenomatous polyposis; NSAIDs, non-steroidal anti-inflammatory drugs; NSP, non-starch polysaccharides; RS, resistant starch.
5 To whom correspondence should be addressed Email: john.mathers{at}ncl.ac.uk
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