Dietary Energy Restriction Inhibits Estrogen-Induced Mammary Carcinogenesis in the Female ACI Rat

The female ACI rat is a unique and physiologically relevant animal model for the study of breast cancer etiology in that it is highly susceptible to the development of estrogen-induced mammary cancer but rarely develops mammary cancer spontaneously. Data from our laboratory indicate that the genetic basis of the susceptibility of the ACI rat to estrogen-induced mammary cancer development is distinct from the more widely used dimethyl-benz[a]anthracene-induced mammary cancer model. It is well established that dietary energy restriction inhibits carcinogen-induced mammary carcinogenesis in rodents. However, the effect of dietary energy restriction on estrogen-induced mammary cancer development has yet to be determined. The purpose of the present study was to investigate whether dietary energy restriction inhibits mammary carcinogenesis induced by 17beta-estradiol ([E.sub.2]) in female ACI rats. To test this hypothesis, we examined the incidence of mammary tumors and precancerous lesions in [E.sub.2]-treated female ACI rats fed a 40% energy-restricted diet. The effects of dietary energy restriction and estrogen on mammary tumor latency, multiplicity and size were also examined. To address the mechanisms through which dietary energy restriction might exert its inhibitory effects on [E.sub.2]-induced mammary cancer development, we examined progesterone receptor expression and cell proliferation in the mammary epithelium of [E.sub.2]-treated rats fed the energy-restricted diet. The data presented indicate that dietary energy restriction inhibits [E.sub.2]-induced mammary cancer development in female ACI rats apparently by inhibiting the progression of precursor lesions into carcinomas. The potential involvement of progesterone receptor expression and mammary cell proliferation in the ability of dietary energy restriction to inhibit [E.sub.2]-induced mammary carcinogenesis is also discussed. [Supported by grant 97A146 from the American Institute for Cancer Research and grants CA68529 and CA77876 from National Institutes of Health.]