Dose-effect studies on estrogen induced mammary cancers in mice

Castrated male (C3H X RIII) F1 mice were treated with graded doses of estradiol-17-beta and estrone in a life-span experiment. Estradiol-17-beta incorporated into paraffin pellets was implanted under the skin for continuous resorption. These pellets contained 1 microgram, 2.5 microgram, 5 microgram, 10 microgram or 100 microgram of hormone. Estron was given orally, mixed with the food at 3 daily dosages: 0.06 microgram, 0.6 microgram and 6 microgram. Although the smallest dosages of both hormones induced vaginal estrus in castrated females, they did not produce mammary tumors. The mammary tumor incidence reached progressively almost 100% in response to the increase of the hormonal dosages. The absence of effect of low doses of estrogen in mice is compared with the absence of an excess of breast cancers among women using oral contraceptives.