Energy availability and mammary carcinogenesis: effects of calorie restriction and exercise

The purpose of this experiment was to compare the carcinogenic response in the mammary gland among groups of rats whose energy metabolism had been modulated by restricting dietary calories and/or by increasing energy expenditure via exercise. Female F344 rats (n = 132) were injected i.p. with 1-methyl-1-nitrosomethylurea (50 mg/kg at 50 and 57 days of age) and were randomized into one of four treatment groups: (i) unrestricted, sedentary; (ii) calorie-restricted, sedentary; (iii) unrestricted, exercised; (iv) calorie-restricted, exercised. The targeted level of calorie-restricted was 20% and exercise was achieved by treadmill-running (20 m/min at a 15% grade for 30 min, 5 days/week). During the 20.5 week study, rats were palpated twice a week for detection of mammary tumors and urine was collected for determination of 24-h cortical steroid excretion. At the end of the study, all mammary lesions were histologically classified. Carcass composition and carcass energy were determined. Mammary carcinogenesis was inhibited among calorie-restricted, sedentary rats compared with unrestricted, sedentary rats (79% inhibition, P < 0.001). No inhibition of carcinogenesis was observed among exercised rats (unrestricted or calorie-restricted) relative to the unrestricted, sedentary rats. Within the present experimental design, exercise had no effect on carcinogenesis despite significant reductions of carcass fat and carcass energy among both groups of rats that exercised. Cortical steroid level was significantly higher only in calorie-restricted, sedentary rats (P < 0.05). These results do not support the hypothesis that reductions of body weight gain, carcass fat or carcass energy are sufficient conditions to inhibit mammary carcinogenesis. The results do suggest that changes in urinary cortical steroid excretion may predict whether an energy-related intervention is likely to alter mammary carcinogenesis.