Genistein studies in rats: potential for breast cancer prevention and reproductive and developmental toxicity.

Asian women and men who consume a traditional diet high in soy products have low incidences of breast and prostate cancers, respectively. Yet Asians who immigrate to the United States and adopt a Western diet lose this protection. We investigated the potential of genistein, a component of soy, to protect against breast cancer and to cause reproductive and developmental toxicity. Our study showed that injections of genistein in rats during the prepubertal period resulted in a 50% reduction of chemically induced mammary tumorigenesis. Studies in mammary whole mounts revealed that prepubertal genistein exposure resulted in fewer terminal end buds and more lobules type II. Cell proliferation in the terminal end buds of adult rats treated prepubertally with genistein was less than that in animals treated with the vehicle (dimethyl sulfoxide). Reproductive and developmental toxicity studies did not find significant alterations to fertility, number of male and female offspring, body weight, anogenital distance, vaginal opening, testes descent, estrus cycle, or follicular development. We concluded that pharmacologic doses of genistein given to immature rats enhance mammary gland differentiation, resulting in a significantly less proliferative gland that is not as susceptible to mammary cancer. We speculate that breast cancer protection in Asian women consuming traditional soy-containing diets is, in part, derived from early exposure to genistein-containing soy. We believe that early programming events are essential for cancer protection benefits.