International variations in cancer rates have been attributed, at least in part, to differences in dietary intake. Recently, it has been suggested that consumption of soyfoods may contribute to the relatively low rates of breast, colon, and prostate cancers in countries such as China and Japan. Soybeans contain a number of anticarcinogens, and a recent National Cancer Institute workshop recommended that the role of soyfoods in cancer prevention be investigated. In this review, the hypothesis that soy intake reduces cancer risk is considered by examining relevant in vitro, animal, and epidemiological data. Soybeans are a unique dietary source of the isoflavone genistein, which possesses weak estrogenic activity and has been shown to act in animal models as an antiestrogen. Genistein is also a specific inhibitor of protein tyrosine kinases; it also inhibits DNA topoisomerases and other critical enzymes involved in signal transduction. In vitro, genistein suppresses the growth of a wide range of can...

Soy intake and cancer risk: A review of the in vitro and in vivo data

Risk assessment of the mycotoxin zearalenone.

Safety and efficacy

Estrogen antagonists are widely used in the treatment of breast cancer, and studies of their mechanism of action may provide clues to an understanding of tumor growth regulation and mechanisms ofnormal estrogen action. We have used human breastcancer cells in long term culture as an in vitro model tostudy the roles of estradiol and the antiestrogens, tamoxifenand nafoxidine, on cell growth and progesteronereceptor (PgR) induction.

Estrogen Control of Progesterone Receptor in Human Breast Cancer: Role of Estradiol and Antiestrogen*

Nuclear mechanisms of estrogen action. Effects of estradiol and anti-estrogens on estrogen receptors and nuclear receptor processing.

The relationship between nuclear retention or residency or receptor estrogen complexes and the agonistic and antagonistic properties of estriol was examined. Cytoplasmic estrogen receptor (Rc) and uterine weight were measured 24 and 48 h after treatment with estradiol (E2), estriol (E3), or or both hormones (E2 and E3). Levels of Rc were elevated in all groups at either time. Since levels of Rc were above control in each case, Rc does not appear to be the limiting factor in the antagonistic effect of estriol. Therefore, the effect of these steroids on translocation and retention of nuclear receptor estrogen complexes (RnE) was examined. Rats were injectd as above and RnE measured by 3[H] estradiol exchange 1, 3, and 6 h after injection. All treatments cause equal translocation of receptor of the nuclear compartment. However, by 6 h the quantity of Rn present in E2 treated animals was significantly above controls while that in E2 + E3 animals was intermediate. E3 alone failed to cause significant nuclear retention of Rn. These patterns of retention correlate with the weight and cytoplasmic receptor responses above and suggest that the short nuclear residency time of RnE3 complexes relates to the antagonism of E3. To test this, these estrogens were administered via paraffin pellets to maintain blood levels of each hormone. Levels of Rn were elevated 24 and 48 h after implant with no significant differences between treatment groups. Likewise, there were no differences in the growth response. Uterine weights were highly stimulated in all three cases (300% above control). These results indicate that E3 acts as an estrogen antagonist when injected as a bolus because of the short nuclear retention time of RnE3 complexes. However, when E3 is present continuously and RnE3 is elevated and maintained, E3 is a potent estrogen without antagonistic properties.

Zigmund Paszko

Papers

Nuclear binding and retention of the receptor estrogen complex: relation to the agonistic and antagonistic properties of estriol.