Oocyte destruction and ovarian tumorigenesis after direct application of a chemical carcinogen (9:10‐dimethyl‐1:2‐benzanthrene) to the mouse ovary

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Abstract
Ovaries of immature mice were painted with 9:10‐dimethyl‐1:2‐benzanthracene (DMBA), and the effect of the carcinogen on the number of oocytes as well as on the subsequent development of ovarian tumours was studied.DMBA had an immediate effect on the small oocytes. Their number was rapidly reduced within the first 4 weeks after treatment, followed by a more gradual elimination, comparable to the elimination rate in the control ovaries. The growing and large oocytes were not primarily affected by the carcinogen; however, after the first 4 weeks post treatment their number was also decreased. This was considered to be secondary to the reduction in the number of small oocytes. No more oocytes remained in the ovaries of 6‐ to 9‐month‐old treated animals, an age at which considerable numbers were still present in the ovaries of control mice.Simultaneously with the elimination of oocytes there occurred a pathological development in the ovaries. There seemed to be a positive correlation between the rate of oocyte disappearance and the pathological development: the faster the oocytes disappeared the earlier the abnormal development began. This ultimately led to ovarian tumours, only seen in ovaries totally depleted of oocytes.It is concluded that DMBA applied to the ovaries acts directly on the small oocytes and destroys many of them. The neoplastic development is considered secondary to the reduction of the oocyte population and is apparently not caused by the carcinogen itself. This is supported by the fact that the development of ovarian tumours in mice is always preceded by a rapid disappearance of oocytes, regardless of whether the method of tumour induction in X‐irradiation, intrasplenic transplantation of an ovary after gonadectomy, treatment with a chemical carcinogen, or genetic deletion of oocytes.