Inhibition of radiogenic mammary carcinoma in rats by estriol or tamoxifen.

Abstract

Mammary carcinomas have been induced by 3.5 Gy whole-body gamma radiation administered at age 40 to 50 days to virgin female Sprague-Dawley rats. In 142 irradiated controls carcinoma incidence averaged 7.8% in survivors observed less than 300 days and 38.3% of those surviving longer (P less than 0.001 by t test). Mammary cancer promotion was inhibited by two methods: estriol (E3) 638 micrograms/month (2.2 microns/mo) subcutaneously for natural life span begun 2 weeks after exposure reduced cancer incidence from 76% in controls to 48% after 331 to 449 mean days observation until neoplasia was palpable (P less than 0.02 by chi-square analysis). Uterine weights were similar in control and treated groups, and were 15% to 18% greater than uteri of nonirradiated controls from other simultaneous experiments. Six monthly 638-micrograms doses of 17 alpha ethinyl estriol (EE3) reduced tumors from 88% in controls to 64% (P less than 0.05 by chi-square analysis) and delayed cancer onset (P less than 0.01-0.04 by life table analysis). Ethinyl estradiol (EE2) after 6 months' treatment similarly delayed mammary tumor development reducing incidence to 75% (NS), with a six-fold increase in nonmammary epithelial malignant tumors. Estriol administration begun between 3 days before to 5 days after radiation did not alter mammary cancer incidence in six experiments. Monthly implantation of 2.5 mg tamoxifen (4.44 microns/mo) started 2 weeks after radiation reduced mammary cancer incidence from 83% to 14% after 307 to 314 days' observation (P less than 0.001 by chi-square analysis). Treated rats had atrophic ovaries and uteri consistent with blockade of endogenous estradiol activity. Short-term parenteral E3 or EE3 therapy using 10 to 30 micrograms/kg/day (35-100 microns/kg/day) rapidly differentiated virgin rat mammary glands without impairment of subsequent estrus cycles and offers an alternative to castration or life-long antiestrogen therapy for reduction of risk of radiogenic mammary carcinoma.

• Authors: H M Lemon, P F Kumar, C Peterson, J F Rodriguez-Sierra, K M Abbo
• Journal: Cancer (Cancer) Vol. 63 Issue 9 Pg. 1685-92 (May 01 1989) ISSN: 0008-543X [Print] United States
• PMID: 2702580 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Tamoxifen
• ethinyl estriol
• Ethinyl Estradiol
• Estriol

Topics

• Animals
• Body Weight (drug effects)
• Estriol (therapeutic use)
• Ethinyl Estradiol (analogs & derivatives, therapeutic use)
• Female
• Mammary Neoplasms, Experimental (drug therapy)
• Neoplasms, Radiation-Induced (drug therapy)
• Organ Size (drug effects)
• Rats
• Rats, Inbred Strains
• Tamoxifen (therapeutic use)
• Uterus (pathology)