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Induction of Urogenital Anomalies and Some Tumors in the Progeny of Mice Receiving Diethylstilbestrol during Pregnancy¹

First Department of Surgery [T. N.] and Institute for Cancer Research [T. N., T. K.], Osaka University Medical School, Fukushima-ku, Osaka 553, Japan

Pregnant mice were given a single dose (10 µg/g body weight) of diethylstilbestrol (DES) on Days 7 to 19, which correspond to the first to fifth lunar months in humans, after the authors, using a ¹⁴C-labeled compound, confirmed easy placental penetration by DES. Treatment with DES on Days 15 to 19 resulted in the induction of persistent urogenital sinus (15.8 to 92.5%) and hypertrophy of the portio vaginalis (11.8 to 73.3%) in female offspring, and treatment on Days 17 and 19 resulted in the induction of undescended testes and their hypogenesis (70.4 to 73.3%) in male offspring, although treatment with DES at other stages of pregnancy and after birth did not cause these alterations. The incidence of various tumors (lung adenoma, granulosa cell tumor, etc.) increased significantly (31.0 to 37.9%) when DES was given on Days 15 and 17, which correspond to the stage sensitive to other carcinogens. However, adenosis and adenocarcinoma of the vagina were not observed in the offspring.

¹ This paper was prepared at the Department of Genetics (Paper 2080), University of Wisconsin, during the tenure of a Research Training Fellowship awarded from the International Agency for Research on Cancer (WHO). Presented at a seminar of the Rockefeller University in 1974.

² Present address: Department of Genetics, University of Wisconsin, Madison, Wis. 53706. To whom requests for reprints should be addressed.

Received 7/26/76. Accepted 12/17/76.

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