The Mechanism of Induction of Ovarian Tumors in the Mouse by 7,12-Dimethylbenz[a]anthracene. I. Effect of Steroid Hormones and Carcinogen Concentration In Vivo

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Abstract
Granulosa cell tumors arose in 30–42% of ovaries grafted orthotopicaliy into ovariectomized IF × C57 mice. The ovaries were obtained from donor mice treated 24 hours previously with 5 mg 7,12-dimethylbenz[a]anthracene (DMBA) by stomach tube or with 5 mg of carcinogen combined with intraperitoneal injections of progesterone, testosterone, or corticosterone. Granulosa cell tumors of the ovary also appeared in 16–31% of ovariectomized female IF × C57 mice given daily injections for various periods of 0.1 mg β-methasone and implanted with ovaries from donor mice given DMBA. β-Methasone injection had no effect on the function of implanted ovaries from donor mice not given DMBA. Ovarian differentiation was substantially normal and there were no tumors. No tumors arose in ovaries from untreated mice or in those from mice given 5 mg of DMBA by mouth and intraperitoneal injections of 11-deoxycorticosterone or 17α-hydroxyprogesterone. No tumors occurred in ovaries from donors treated 24 hours before with 0.25 mg or less of DMBA by stomach tube. Apparently normal follicles and corpora lutea were seen in transplants of normal ovaries and in those exposed to DMBA and 17α-hydroxyprogesterone. In addition, at least half of these mice had evidence of both estrogen and progesterone secretion at death. Very few or no normal follicles or corpora lutea were seen in ovaries exposed to DMBA alone or 11-deoxycorticosterone or other steroids. Only one mouse treated with steroids showed evidence of progesterone secretion in addition to estrogen secretion. In all mice subsequently developing ovarian tumors, the incidence of vaginal keratinization increased between 10 and 18 weeks after treatment. This increase was not observed in mice bearing ovarian grafts in which tumors did not subsequently develop. All the 28 granulosa cell tumors were associated with evidence of estrogen secretion and 7 had evidence of progesterone secretion as well.

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