Mammary Carcinomas in Mice Following Oral Administration of Stilbestrol

Abstract

Mammary carcinomas are readily induced by long-continued administrations of large doses of estrogens to mice of susceptible strains. In the numerous investigations 1 on the subject, the subcutaneous route of injection has been used almost exclusively. The induction of breast tumors following oral administration of estrogens has not been reported. The natural estrogens lose most of their estrogenic potency when given by mouth, 2 whereas the synthetic product, stilbestrol (4 :4'-dihydroxy-α :β-diethylstilbene) is effective orally, 2 and was used in this experiment.

Forty-one male mice of strain C₃H, raised in this laboratory, were used. Spontaneous mammary tumors develop in practically 100% of the virgin females of this line, but do not occur in the males. 3 The mice were maintained on a standard diet and an unlimited supply of water. They were about 2 months old and weighed from 21 to 23 g when the experiment was initiated.

Stilbestrol∗ was dissolved in sesame oil, and was fed to the mice by means of a curved metal tube passed into the esophagus. The animals were divided into 4 groups: (I) Eleven were given 0.125 mg of stilbestrol dissolved in 0.1 cc of sesame oil twice a week for 17 weeks, for a total dose of 4.25 mg of the compound. (II) Ten received 0.375 mg of stilbestrol in 0.1 cc of sesame oil twice a week for 17 weeks for a total of 12.75 mg. (III) Ten were fed 0.1 cc of sesame oil twice a week for 17 weeks. (IV) Ten were kept as untreated controls.

The first effect noted was the marked retardation in the gain in weight of the mice which were ingesting stilbestrol (Figure 1).