DMA Synthesis and DMA Polymerase Activity in Leydig Cells of Diethylstilbestrol-stimulated Mouse Testes1

Using a modification of the collagenase dispersion method of Dufau et a/., we examined changes in DMA synthesis produced by estrogens in the interstitial cells of mice that develop malignant Leydig cell tumors after prolonged estrogen administration. Previous work in cryptorchid mice indicated that during continuous estrogen administration ['H]thymidine incor poration into DNA rises to a maximum in 3 to 4 days and then falls to approximately base levels within 2 to 3 weeks. This was confirmed both in Leydig cell concen trates of estrogen-treated mice after either injection with [3H]thymidineor incubation with [3H]thymidinein vitro. This DNA synthesis was blocked by hydroxyurea. DNA synthesis in cells of estrogen-treated BALB/c mice of the Huseby substrain, which have a high incidence of Leydig cell tumors, was 5 to 11 times that in untreated controls. Cells from estrogen-treated C3H/BÕmice, which have a low incidence of Leydig cell tumors, showed only a 2to 3-fold increase. In the Huseby substrain the rise of DNA synthesis to a peak and subsequent recession were paralleled by a rise and fall in DNA polymerase a activity. DNA polymerase ß did not show this variation. In C3H/BÕmice, neither polym erase showed significant change. The evidence suggests that the early estrogen-stimulated DNA synthesis is prob ably replicative and is associated with increased DNA polymerase a activity.