Inhibitory Effects of Estrogenic Compounds, 4-Nonylphenol and Genistein, on 7,12-Dimethylbenz[a]anthracene-Induced Ovarian Carcinogenesis in Rats

Abstract 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)- α and - β 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- α , β 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.