Attempts to produce cancer in rhesus monkeys with carcinogenic hydrocarbons and estrogens.

Abstract

This experiment was begun in 1936. There were 50 Rhesus monkeys 47 females and 3 males kept under treatment and observation. 21 females were castrated and 3 were hysterectomized. At the start all were estimated to be 3-10 years old. At first estrogens were administered directly to the breasts dissolved in oil and injected. A variety of estrogens were used. About 5000 IU were injected twice weekly. After 1939 most of the estrogen-treated animals received either estradiol dipropionate or estrone in pellets implanted sc. Carcinogenic hydrocarbons used were methylcholanthrene benzpyrene and benzanthracene in crystalline form. They were dissolved in sesame oil 10 mcg/ml and injected sc or painted on the skin from a benzene solution. The weekly dose of carcinogen varied from 2 to 6 mgm. In many cases various other methods of application were used. Organs and tissues that frequently become cancerous in humans were treated directly. The breasts received the most chronic treatment. Carcinogens were also given iv and orally. Animals were under treatment for long periods until they came to autopsy. After 5-10 years of treatment with estrogens and carcinogenic hydrocarbons 4 monkeys were still alive and in good health. In the 5 years since pellets of carcinogens replaced other methods of application hyperkeratinization and ulcerated lesions have healed leaving scars. Fibrotic masses and papillae while still present have receded in size. Areas of granulation tissue and encapsulated cysts often occurred. Pellets became encapsulated by dense fibrous tissue. Lesions often became infected and ulcerated. Metaplasia of mammary ducts and of the uterine cervix occurred but did not progress. Malignant tumors were not produced in any tissue or organ.