Intestinal tumorigenesis in the Apc1638N mouse treated with aspirin and resistant starch for up to 5 months

The Apc1638N mouse model, which carries a targeted mutant allele within the adenomatous polyposis (Apc) gene and develops intestinal tumours spontaneo usly, predominantly in the small bowel, was used to investigate the effects of two potential chemopreventive agents, aspirin and a-amylase resistant s tarch (RS), Heterozygous Apc+/ Apc1638N mice were fed semi-purified diets r ich in animal fat, animal proteins and sucrose and low in dietary fibre (We stern style diets) from similar to 6 weeks up to 6 months of age. Two of th e diets contained aspirin (300 mg/kg diet) and two RS (1:1 mixture of raw p otato starch: Hylon VII at 200 g/kg diet) in a 2X2 factorial design, A fift h treatment group were fed a conventional rodent chow diet. The mice fed th e 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 signif icantly more intestinal tumours whereas aspirin alone had no effect. Howeve r, there was a significant aspirin x RS interaction, which suggests that as pirin could prevent the small intestine tumour-enhancing effects of RS in t his Ape-driven tumorigenesis model, The possibility that large amounts of p urified forms of resistant starch may have adverse effects within the small bowel is a novel observation that requires further investigation since gre ater intakes of starchy foods land 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 germl ine mutations in APC.