Mechanism of Induction of Ovarian Tumors in the Mouse by 7,12-Dimethylbenz[a]anthracene. III. Tumor Induction in Organ Culture

Summary

Ovaries were removed from immature mice, maintained in organ culture for periods ranging from 4 hours to 4 days, and then reimplanted subcutaneously into the same mice from which they were obtained. A granulosa-cell tumor arose in only 1 of 87 mice whose ovaries had been exposed to the culture medium only. Addition of 7,12-dimethylbenz[a]anthracene (DMBA) to the organ culture medium in concentrations varying between 0.5 and 4 μg/ml resulted in incidences of granulosa-cell tumors ranging from 7–60% in (BALB/cJ ♀ × A/J♂)F₁ (CAF₁/J) mice and 44% in one experiment at a concentration of 4 μg/ml of DMBA in hybrids of C3H and NZY mice. The incidence of granulosa-cell tumors reached a significantly greater level than the controls with 1.0 or 4.0 μg/ml of DMBA but not with 0.5 μg/ml. Adding 10 μg/ml of various steroids to the medium did not result in any significant incidence of granulosa-cell tumors. In experiments in which steroids at 10 μg/ml were added to medium containing 4 μg/ml of DMBA, the incidence of tumors was lower in 3 groups than with DMBA alone, i.e., 17-hydroxyprogesterone 0/9, deoxycorticosterone 2/25, and 4-pregnen-3β,20β-diol 1/14, but 5 other steroids did not affect tumor induction. Luteomas were equally common in both control and carcinogen-treated ovaries, but were less frequent in ovaries exposed to steroids alone. Injecting chorionic gonadotropin after reimplantation did not influence the yield of ovarian tumors. Hyperplasia of type-B cells of the adrenal cortex, together with vaginal mucification, was associated with the complete absence of ovarian tissue or the presence of ovaries that had been treated with DMBA.