Inhibition of radiogenic mammary carcinoma in rats by estriol or tamoxifen.
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.
Lemon
H M
HM
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105.
Kumar
P F
PF
Peterson
C
C
Rodriguez-Sierra
J F
JF
Abbo
K M
KM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004964:Estriol / Q000627:therapeutic use*; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000627:therapeutic use*; D014599:Uterus / Q000473:pathology
D013629:Tamoxifen; C059181:ethinyl estriol; D004997:Ethinyl Estradiol; D004964:Estriol