Protective effects of physiological doses of estrogen during hepatocarcinogenesis induced by diethylnitrosamine and N-nitrosomorpholine.

Concern that much controversy exists with respect to the role of estrogen in hepatocarcinogenesis prompted us to examine the effect of estrogen, at physiological concentrations, on our established HCC rat model induced by diethylnitrosamine and N-nitrosomorpholine. Female Sprague-Dawley rats were randomly divided into four groups (Group 1: Control, Group 2: Sham-operated, Group 3: Ovariectomy, Group 4: ovariectomy+estrogen) with treatment of a single i.p. injection of diethylnitrosamine (100mg/ kg body weight) followed by N-nitrosomorpholine (100ppm) in drinking water for 20 weeks for the established rat HCC model. Physiological estrogen was administered by 17α-Ethynylestradiol at a dose of 30μg/ kg body weight while rats in the sham-operated group were treated with saline after initiation of liver carcinogenesis. Treatment of ovariectomized animals with 17α-Ethynylestradiol (30μg/kg body weight/ day) resulted in a significant decrease in the initiation, development and metastasis of HCC and an increase in the survival time of animals dead before the termination of experiment as compared with rats treated with ovariectomy only (p<0.05); whereas this difference disappeared when compared with the other three groups. These findings show for the first time that estrogen, at physiological concentrations may reveal a protective role in hepatocarcinogenesis.