Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring

A high estrogenic environment in utero may increase subsequent breast cance r risk. It was therefore determined whether a maternal exposure during preg nancy to the phytoestrogen genistein or zearalenone, both of which exhibit estrogenic activities in vitro and in vivo, alters breast cancer risk among female offspring. Pregnant rat dams were treated daily with subcutaneous i njections of 20, 100 or 300 mu g genistein, 20 mu g zearalenone, or vehicle between days 15 and 20 of gestation. The offspring were given 7,12-dimethy l-benz(a)anthracene (DMBA) at the age of 2 months to induce mammary tumors. The results indicate that in utero exposure to genistein, but not to zeara lenone, dose-dependently increased the incidence of DMBA-induced mammary tu mors, when compared with the controls. Tumor growth characteristics were no t altered. Prior to the carcinogen administration, the number of estrogen r eceptor (ER) binding sites, determined using a ligand binding assay, were s ignificantly elevated in the mammary glands of genistein offspring. In cont rast, the mammary protein kinase C (PKC) activity was significantly reduced in the genistein offspring. Our results suggest that a maternal exposure t o subcutaneous administration of genistein can increase mammary tumorigenes is in the offspring, mimicking the effects of in utero estrogenic exposures . Further, increased ER protein levels and reduced PKC activity in the mamm ary gland may be involved in increasing susceptibility to carcinogen-induce d mammary tumorigenesis in rats exposed to genistein in utero.