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Rats of relatively low susceptibility to spontaneous carcinoma were studied. The estrone used was crystalline folliculin. Experiment 1 inv olved 12 rats, of which half were ovariectomized at the age of 58 days. All animals received daily vaginal application of a solution of estrone in corn oil from the age of 62 days until death. Hysterectomy was done on some to remove pyometra. Some were painted on the interscapular region 3 times a week with tar. In 2 cases, 3 mg of dry kieselguhr were inserted into 1 mammary gland. In this series, 1 rat killed on the 964th day of life had squamous carcinoma of the vagina, a precancerous lesion of the cervix, and a mammary adenofibroma. Another rat, at the age of 751 days, had a large abscess adherent to the descending colon. In the wall of the abscess a squamous cell carcinoma was found. In other rats of this group, a cervical papilloma and an ileo-caecal lymphosarcoma were found. In the 2nd series, 10 rats were ovariectomized at 106 days of age and silk threads placed in 1 or both uterine horns. All of these rats received daily sc injections of 30 gamma of estrone in corn oil. Some also had silk threads or kieselguhr placed in 1 mammary gland. A rat in this group, killed on Day 293 of life, had a precancerous lesion of the cervix and an abdominal lymphosarcoma. Another rat at the age of 624 days had an adenocarcinoma of the breast and 49 days later an abscess in the lower abdomen. In the wall of the abscess squamous pearls of doubtful malignancy were found. In the same rat there was an area of squamous metaplasia in a breast where kieselguhr had been injected. In a control series of 12 rats injected with corn oil alone or not treated, squamous lesions were found in abscesses of uterine horns of 2 at 753 days. A 3rd series consisted of 12 female rats of which 6 were ovariectomized at the age of 116 days. All received daily injections of 30 gamma estrone. Kieselguhr, 15 mg, was placed in the uterine horns of each animal and 35 mg in the peritoneal cavity of some. A malignant breast tumor developed in 1 rat at the age of 553 days. When estrone injections were stopped, the tumor ceased to grow. Another rat in this group died of abdominal lymphosarcoma. Of 12 rats in the 3 series which survived 500 days or longer and were treated with estrone, 4 developed cancer while of 18 control rats from Series 2 and 3 living 500 days or more only 1 had cancer. Fistulas between the uterus or vagina were found only in estrone-treated rats. In this colony of 121 rats kept without treatment, 55 female and 27 males survived 500 or more days. A submaxillary gland cancer was found in 1 but no other malignant tumors occurred among them. It is concluded that rats treated for long periods with estrone, often toghether with various forms of local irritation, developed malignant tumors more frequently than others of the same colony subjected to other procedures or untreated.

Occurrence of cancer in rats treated with oestrone.