Effect of sex hormones on the carcinogenic action of dimethylbenzanthracene on the uterus of intact and castrated mice.

Contradictory reports have appeared in the literature on whether estrogens and ovariectomy reduce the incidence of malignant uterine lesions. To investigate this problem the author experimented with 260 CF1 mice exposed to 910-dimethyl-12-benzanthracene (DMBA) in contact with the cervix or the endometrium. There were 9 groups: 1) 59 mice treated with 1-2 mg of DMBA in contact with the cervix; 2) 53 mice receiving 1 mcg of alpha estradiol a week for life; 3) 10 mice receiving 10 mcg of alpha estradiol a week for life; 4) 17 mice receiving 28 mcg of testosterone propionate a week for life; and 5) mice into which 1-2 mg of DMBA was placed in contact with the endometrium. 4 similar groups were formed with ovariectomized mice as follows: 1) 48 spayed mice with no hormonal treatment; 2) 55 mice received alpha estradiol as in group 2; 3) 8 mice receiving testosterone propionate as in group 4; and 4) 5 castrated mice with DMBA in contact with the endometrium. DMBA was left in place for 1-6 weeks in 136 mice and for life in the remaining 124. 88 animals were kept as controls. When malignant cells appeared in vaginal smears or tumors became obvious the animals were killed and observed. There was no incidence of malignant growth among controls. In DMBA-exposed mice the overall incidence was 41.9% or 49.3% of intact and 32.7% of ovariectomized mice. Intact mice in group 2 receiving estradiol had an incidence of 41.5% while those in group 4 receiving testosterone had an incidence of 64.7%. In the series of 124 exposed mice to DMBA for life the overall incidence was 57.2% the difference between intact 69.1% and ovariectomized mice 42.8% being significant. In animals given 1 mcg of estradiol the incidence was 39% in those without hormonal treatment it was 65.7%. The lowest incidence 25% was in ovariectomized mice receiving estradiol; the highest 80% in mice receiving the 10-fold dosage of estradiol and in those exposed to DMBA in the uterus. In the series of 136 mice exposed to DMBA for 1-6 weeks the overall incidence was 17.9% or 4.1% after 1 week and 52.6% after 6 weeks. The average latent period was shortest in animals treated with testosterone and the longest intact mice with DMBA in the uterine horn. Variations in weight were not statistically significant. 13.4% of mice had moderate to severe dysplasia; 41.9% had malignant lesions in the vaginal vault and in the uterus. Analysis of the results of Papanicolaou smears showed that castration produced a drop in the incidence of estrus. The most significant finding of this study was the decrease in the incidence of malignant tumors with estrogen treatment and after ovariectomy. The dose of 1 mcg of estradiol roughly comparable to 1-2 mg a week in women significantly reduced the incidence of uterine cancer while the dose of 10 mcg increased it. The lower incidence of lesions in castrated mice may suggest that progesterone has a promoting role in influencing malignant lesions; more studies are needed to clarify this question. This study did not show any correlation between hormone treatment and/or ovariectomy and the histologic nature of uterine lesions.