title: Protective effects of physiological doses of estrogen during hepatocarcinogenesis induced by diethylnitrosamine and N-nitrosomorpholine.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings show for the first time that estrogen, at physiological concentrations may reveal a protective role in hepatocarcinogenesis.
authors.affiliation: Anhui Medical University, Hefei, China.
authors.forename: Yong-Cang
authors.initials: YC
authors.lastname: Wang
authors.forename: Ge-Liang
authors.initials: GL
authors.lastname: Xu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Jia
authors.forename: Sheng-Jin
authors.initials: SJ
authors.lastname: Han
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Ren
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Liu
authors.forename: Chuan-Hai
authors.initials: CH
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity; D004958:Estradiol / Q000627:therapeutic use*; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D009602:Nitrosamines / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009602:Nitrosamines; D004052:Diethylnitrosamine; C002741:N-nitrosomorpholine; D004958:Estradiol