Effect of energy restriction on tissue size regulation during chemically induced mammary carcinogenesis

Energy restriction (ER) has documented beneficial effects on numerous disea ses including cancer, yet the mechanism(s) that accounts for these effects is unknown. Experiments were designed to determine the effect of ER: (i) on the growth and development of the mammary gland; (ii) on the growth of car cinomas induced in the mammary gland by treatment with l-methyl-l-nitrosour ea (MNU); (iii) on rates of cell proliferation and apoptosis in premalignan t and malignant mammary lesions. Mammary carcinogenesis was induced in fema le Sprague-Dawley rats by the i.p. administration of MNU (50 mg MNU/kg body wt) at 21 days of age. Rats were randomized to one of four dietary treatme nt groups: ad libitum fed or restriction of calorie intake to 90, 80 or 60% of ad libitum intake. ER reduced the ductal extension of the mammary gland into the fat pad in proportion to its effect on growth measured as body we ight, however, the reduction in ductal branching, breast density and carcin oma volume by ER was greater than its effect on body weight. An animal's br east density was predictive of its carcinogenic response, irrespective of t he level of ER imposed. While ER inhibited cell proliferation and induced a poptosis in pre-malignant and malignant mammary gland lesions, the magnitud e of these effects make it unlikely that they fully account for the protect ive effects of ER against mammary carcinogenesis.