Production of Carcinoma of the Uterus in Mice

Spayed and normal young adult female mice were treated twice a week with a .3% solution of 1:2:5:6 dibenzanthracene and a 0.1% solution of estrone∗ painted on the nape of the neck. Benzene was the solvent for both substances. Treatment with estrone was begun 9 weeks after the treatment with 1:2:5:6 dibenzanthracene because of its more rapid action. Twelve weeks after the treatment with estrone was begun the dose was cut in half because of the development of pyometria. The original dose was estimated to be 125 R.U. Treatment was continued throughout the life of the animals. Six months after the 1:2:5:6 dibenzanthracene treatment was begun there were 27 mice in the group when a mouse died with a large epidermoid carcinoma of the cervix. In the tenth month of the experiment 2 other cases of epidermoid carcinoma of the cervix occurred. These were in the last mouse surviving in the spayed and in the normal group. Both of these mice built nests persistently in the last weeks. All of the animals developed marked hyperplastic, cystic, and metaplastic changes in the breast and uterus. Forty-three percent of the colony developed carcinoma of the breast. Two of the mice developing carcinoma of the cervix: had carcinomas of the breast and pyometria. Pyometria and carcinoma of the breast set a pathological limit to the amount of estrone which can be long tolerated. The mouse is not susceptible to spontaneous carcinoma of the uterus. Slye in 39,000 autopsies had only one possible case. No other workers have produced carcinoma of the uterus without direct irritation of the organ, nor have they maintained animals so long on so large a dose of estrone.