Rapid induction of ovarian granulosa cell tumors by 7,12-dimethylbenz(a)anthracene in neonatally estrogenized mice.
Groups of female C3H/HeMs x 129/J F1 mice were given injections of either 20 micrograms of 17 beta-estradiol or sesame oil (vehicle) for the first 5 days after birth. Half of each group was then given gastric intubations of 20 mg/kg of 7,12-dimethylbenz(a)anthracene (DMBA) at 70, 77, and 84 days of age. The other half of each group was given sesame oil. Thus, this design yielded four experimental groups: oil + oil; 17 beta-estradiol + oil; oil + DMBA; and 17 beta-estradiol + DMBA. They were sacrificed at approximately 144 days of age (Experiment 1) or the day of palpable ovarian tumor detection or 360 days of age (Experiment 2). In Experiment 1, the total number of oocytes (follicles) per ovary in mice of the 17 beta-estradiol + oil group was maintained at the same level as mice of the oil + oil group. A significant reduction of oocytes, however, was observed in mice of the 17 beta-estradiol + DMBA group in comparison with mice of the oil + DMBA group (P less than 0.01), and neoplastic nodules of the granulosa cell type developed in the unilateral ovary in 10 of 17 mice of the 17 beta-estradiol + DMBA group. No tumors were detected in the mice of the other groups. The plasma levels of both follicle-stimulating and luteinizing hormones as determined by radioimmunoassay were significantly higher (P less than 0.01) in mice of the 17 beta-estradiol + oil group than in mice of the oil + oil group. In Experiment 2, more ovarian tumors of the granulosa cell type were detected before 360 days of age in mice of the 17 beta-estradiol + DMBA group (14 of 18) than in mice of the oil + DMBA group (5 of 15) (P less than 0.05). No tumors developed in mice of the other two groups. These results strongly indicate that an abnormal endocrine milieu caused by neonatal treatment with estrogen may induce a high frequency of transformation of some ovarian tissues and rapid growth of the ovarian tumors after DMBA treatment.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000831:Animals, Newborn; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006062:Gonadotropins / Q000097:blood; D006106:Granulosa Cell Tumor / Q000139:chemically induced* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D010051:Ovarian Neoplasms / Q000139:chemically induced* / Q000473:pathology; D010053:Ovary / Q000473:pathology
D004967:Estrogens; D006062:Gonadotropins; D015127:9,10-Dimethyl-1,2-benzanthracene