Experimental Studies upon Ovarian Tumors Induced with 7, 12-DMBA in Mice

Daily examination of the vaginal smears of mature C3H mice was carried out more than 1 year. The control 21 mice showed almost regular estrous cycles in the duration of the age of 2 to 12.5 months. Twenty-eight mice, injected by 2.5 mg of DMBA at the age of 52 or 59 days, could not reveal a regular appearance of estrous cycle in the whole life after the single injection. The DMBA-injected mice were begun to be examined the vaginal smears at the age of 45 days, and devided to 4 experimental groups, depending on the stage of estrous cycle in which the single injection was performed. These groups were neither connected to the type of following irregular estrous cycles, to the incidence of the ovarian tumors, nor to the histological pattern of the established ovarian tumors.DMBA promoted to reveal an estrus-stage immediately after the single injection, and produced a diestrus-dominant stage 1-4 weeks after the injection. This biological phenomen suggested DMBA could injure the estrogen-producing cells directly.Four types of irregularity of the following estrous cycles after the injection of DMBA were classified. The 1st type was almost regular as same as the controls and could not be observed on the experimental groups. The 2nd type was very irregular and showed a continuous diestrus in the latter half period of the experiment. The 3rd type was extremely irregular and showed a continuous estrus in the latter half period. Number of the mice in the 2nd or 3rd type was almost the same each other, and less half of the treated animals.The 4th type, about 10% of the injected mice, showed no estrus in the life after the injection. The last type was subdivided a- and b-subtype. IV-a type revealed never estrus in all life span. IV-b type showed few estrus in the course after the injection, even estrus was almost always detected immediately after the single injection. The mice showing II type had atrophic ovaries, small luteoma, cystoma and blood yst without thecal cell proliferation, or follicular type granulosa cell tumors. Incidence of the macroscopic tum or in II type was 33%. The mice showing III type beared diffuse. type of undifferentiated granulosa cell tumor, or the abnormal ovaries with thecal cell proliferation, in which lutein cells hardly be detected. The induction rate of ovarian tumors was macroscopically 69%in III type. The IV-typed mice had hypoplastic ovaries and no ovarian tumors macroscopically.Estrogen-producing cells in the DMBA-induced ovarian tumors of C3H mice would be the proliferated thecal cells and interstitial gland cells in the tumor, or undifferentiated tumor cells close-related by sex-cord mesenchymal cells.