Exercise and intestinal tumourigenesis in the Min mouse

Abstract

Colon cancer is the third most frequently diagnosed cancer in the UK and is often associated with a "Western" style of eating, high in fat and low in vegetables and fruits. There is strong epidemiological evidence that more physical activity is associated with reduced risk of colon cancer, but the amount or type of activity necessary to invoke this protection is disputed, and the mechanism responsible has not been elucidated. In this project, Min mice were used in studies of the impact of physical activity on development of intestinal neoplasia. These mice have a mutation at codon 850 in the Apc gene and develop multiple intestinal polyps spontaneously. The numbers, sizes and anatomical distribution of these lesions can be altered by dietary and pharmacological agents. From 5 weeks of age, male and female Min mice were exercised by running on a treadmill at up to 21 m/min for 30-60 min on a 5% slope for 5d/week for 10 weeks (TR). Additional groups of mice were provided with an exercise wheel (WH) or with no exercise (CON). Throughout the study, mice had ad libitum access to a Western-style high fat diet. Interleukin (IL)-6, IL-10, caecal transit time, colonic short chain fatty acids and natural killer cell cytotoxicity were investigated as potential protective mechanisms. On average, WH mice ran 2.99km/d (maximum 18.35km/d) compared with a maximum 0.96km/d for TR mice. Female mice were more willing treadmill runners and ran further in the wheels than did males. There was no significant reduction in total number of turnours or tumour burden in TR or WH compared with CON mice. Molar proportion of butyrate was significantly greater in TR mice compared with CON (P = 0.002). None of the other investigated mechanisms were different between exercise groups, although sex differences were observed for transit time. Non-exercise physical activity (NEPA) undertaken by the TR and CON mice was quantified for 23h per day (i. e. excluding period associated with treadmill running) using an Inframot device. NEPA was significantly higher for TR compared with CON mice (P=0.00 1), and for females compared with males (P<0.00 1). This study demonstrates that the tumour load in Min mice fed a high fat diet is not modulated by an exercise regime.