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.
Tanaka
Takuji
T
The First Department of Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan. takutt@kanazawa-med.ac.jp
Kohno
Hiroyuki
H
Tanino
Mikio
M
Yanaida
Yoshitame
Y
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000009:adverse effects; D000230:Adenocarcinoma / Q000139:chemically induced* / Q000517:prevention & control* / Q000662:veterinary; D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000008:administration & dosage / Q000009:adverse effects; D002471:Cell Transformation, Neoplastic; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000139:chemically induced* / Q000517:prevention & control* / Q000662:veterinary; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D010636:Phenols; D015127:9,10-Dimethyl-1,2-benzanthracene; D019833:Genistein; C041594:4-nonylphenol