Inhibitory effects of estrogenic compounds, 4-nonylphenol and genistein, on 7,12-dimethylbenz[a]anthracene-induced ovarian carcinogenesis in rats.

The modifying effects of dietary feeding of estrogenic compounds, 4-nonylphenol (4-NP) and genistein (GS), on 7,12-dimethylbenz[a]anthracene (DMBA)-induced ovarian carcinogenesis were investigated in female Sprague-Dawley rats. We also assessed the effects of test compounds on proliferating cell nuclear antigen (PCNA) index and the expression of estrogen receptor (ER)-alpha and -beta and androgen receptor (AR) in induced neoplasms. Rats were given a single injection of DMBA (0.01 ml of 0.5- DMBA suspended in olive oil) into their left ovary to induce ovarian neoplasms. They also received the experimental diet containing 25 to 250 ppm 4-NP or GS for 50 weeks, starting one week after the dosing of DMBA. DMBA exposure produced ovarian adenocarcinoma with an incidence of 35% at the end of the study (Week 51). Dietary administration of 4-NP or GS caused significant reduction in the incidence of ovarian adenocarcinoma: 86% reduction (P=0.0218) by feeding of 25 or 250 ppm 4-NP and 25 ppm GS, and 100% reduction (P=0.0042) by feeding of 250 ppm GS. The PCNA index in adenocarcinomas was higher than that of surface ovarian epithelium. ER-alpha, beta and AR were expressed in a variable percentage of moderately and poorly differentiated adenocarcinoma cell nuclei, but not in well-differentiated adenocarcinoma cells. These results might suggest that dietary feeding of estrogenic compounds either synthetic (4-NP) or natural (GS) could act as an inhibitor of DMBA-induced rat ovarian carcinogenesis.