The overall objective of this research program is to determine the tumorigenic response to various amounts and types of exercise in a well defined model system for breast cancer, and to study the influence of the level of caloric intake and the type and amount of dietary fat on exercise modulated tumor responses. Specifically, the following questions will be addressed: (1) Is the tumorigenic response the same when animals engage in graded levels of : (a) aerobic exercise of moderate intensity and duration, (b) anaerobic exercise of high intensity and short duration, and (c) aerobic exercise of low intensity and prolonged duration? (2) Is the effect of exercise on the tumorigenic response dependent on or independent of energy expenditure? (3) Is the effect of exercise on the tumorigenic response modified by the amount and/or type of dietary fat ingested? (4) Does exercise affect the appearance of ovarian hormone independent mammary tumors? (5) Is the effect of exercise on tumorigenesis modified by adrenalectomy? Mammary carcinogenesis will be induced by 1-methyl-1-nitrosourea (MNU) and evaluated in terms of incidence, latency and tumor multiplicity. Ovarian hormone independent mammary tumorigenesis will be studied via bilateral ovariectomy. Exercise will be performed on a variable beltspeed, incline adjustable rodent treadmill. Aerobic capacity will be assessed as VO2 max. Energy expenditure and respiratory quotient will be determined during exercise and serum levels of fatty acid and cortisol will be quantified. Metabolic cycling between triglyceride and glycerol will be evaluated radiometrically. Purified diet formulations will be used and food provided either ad libitum or on a meal fed basis. Food consumption will be quantified. Effects of exercise and diet on body composition will be determined via the gravimetric analyses of regional adipose depots and chemical analyses of the carcass. The effect of exercise on estrous cycle periodicity will be determined, and exercise-mediated effects on mammary gland development will be assessed in whole mounts preparations. Completion of the proposed work will define both the nature of the tumorigenic response over a broad range of exercise conditions, and establish the influence of energy balance and energy reserves in modulating the process of tumor development.
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