Genistein enhances N-nitrosomethylurea-induced rat mammary tumorigenesis

Genistein is of great interest for its implications as an anticancer compound. We compared the effects of daily subcutaneous injections of 1mg/kg BW of genistein and vehicle (2% DMSO in peanut oil) for 20 weeks on N-nitroso-N-methylurea (NMU)-induced tumorigenesis in adult female rats. Genistein significantly increased tumor cross-sectional area and tumor multiplicity but not the tumor incidence and latency period when compared with the vehicle treated group. The serum E(2) levels of genistein treated group were significantly higher than those of the vehicle treated group at 1 and 2 months after treatment which is the time when most of the rats developed tumors. There were no significant differences in the length of the estrous cycle, food consumption and weights of body, livers, uteri and ovaries between the two groups. Our data shows that supplementation of genistein at a dosage comparable to the isoflavone consumption in humans did not affect the reproductive system but resulted in enhancement of NMU-induced tumorigenesis in adult female rats. Thus, the supplementation of soy isoflavone in premenopausal women may potentially potentiate the risk of breast cancer.