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Inhibition of radiogenic mammary carcinoma in rats by estriol or tamoxifen

1990; Wiley; Volume: 63; Issue: 9 Linguagem: Inglês

10.1002/1097-0142(19900501)63

1097-0142

Henry M. Lemon, Pradeep F. Kumar, Cary Peterson, Jorge F. Rodriguez‐Sierra, Katherine M. Abbo,

Estrogen and related hormone effects

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 < 0.001 by t test). Mammary cancer promotion was inhibited by two methods: estriol (E3) 638 μ/month (2.2 μ/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 < 0.02 by chisquare 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-μg doses of 17 alpha ethinyl estriol (EE3) reduced tumors from 88% in controls to 64% (P < 0.05 by chi-square analysis) and delayed cancer onset (P < 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 μ/mo) started 2 weeks after radiation reduced mammary cancer incidence from 83% to 14% after 307 to 314 days' observation (P < 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 μ/kg/day (35–100 μm/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.