Wheel running exercise and tumorigenesis in ENU-treated in FVB x C57BL/6J ApcMin/+ mice

B72 We examined the effects of wheel running exercise on the development of mammary hyperplasias and tumors, intestinal polyps, and lung tumors in female FVB x B6 F1 mice. Three week-old female mice (n=24/group) were randomly assigned to either a control (CON) or voluntary wheel running condition (WHL), where they were individually housed in a standard cage or with a running wheel, respectively. Mice were given standard rodent breeding diet and water ad libitum, and weighed weekly. At 35-40 days of age, mice were treated with ENU, and euthanized at ~120 days post-ENU treatment for the evaluation of hyperplastic foci and adenocarcinomas in the mammary glands, lung adenocarcinomas, and intestinal polyps. Dual-energy x-ray absorptiometry was used to quantify body fat. WHL mice ran 6.2 ± 2.9 km/day. There was no difference in weekly body weights between groups (p=0.39), and the percent body fat was no different (33.1 ± 1.5 vs. 32.1 ± 2.0 in CON vs. WHL, p=0.68). There was no difference in any cancer endpoint, with similar numbers of mammary hyperplasias (3.3 ± 0.4 vs. 3.4 ± 0.4, p=0.84), mammary tumors (1.1 ± 0.2 vs. 1.2 ± 0.2, p=0.74), time to tumor development (117 ± 7 vs. 96 ± 10 days, p=0.08), number of intestinal polyps (20.7 ± 1.6 vs. 19.3 ± 2.1, p=0.58), and the percent of each group that developed lung tumors (25 vs. 21%, p=0.99) in the CON vs. WHL, respectively. Wheel running did not affect any tumor-related outcome. The similar body weights in the two groups suggest that the WHL mice increased their energy intake to compensate for their increased energy expenditure. This maintenance of energy balance may have negated any beneficial effect of exercise, suggesting that the anti-cancer effects of exercise in this ENU-induced model of carcinogenesis in Apc-deficient mice may be dependent on energy balance modulation.