Suppressive effect of estrogen on hepatocellular tumorigenesis induced in mice by 3′-methyl-4-dimethylaminoazobenzene

Summary Treatment of female C57BL/6 × DS-F 1 mice with 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB) neonatally resulted in the development of hepatocellular adenomatous nodules. Ovariectomy at 1 month of age greatly hastened the time of appearance of these nodules and significantly increased their incidence. The incidence of adenomatous nodules in females ovariectomized at 1 month of age was about 70 % at 12 months of age, and was decreased to 4 % by implantation of a pellet containing estradiol- 17 s (E 2 pellet) at 1 month of age (at the time of ovariectomy). The incidence of adenomatous nodules at 12 months of age was not decreased significantly when the implanted E 2 pellet was removed at 4 or 6 months of age, but was decreased significantly when it was removed at 8 or 10 months of age. Implantation of E 2 pellets into ovariectomized females at 4 and 6 months of age decreased the incidence of adenomatous nodules as effectively as their implantation at 1 month of age. The implantation of E 2 pellets into ovariectomized females at 8 or 10 months of age resulted in significantly lower incidences of adenomatous nodules at 12 months of age, than that in females ovariectomized at 1 month of age. The present results suggest that the ovarian hormone, estrogen suppresses the development of hepatocellular tumors induced by 3′-Me-DAB, exerting its effect from about 6 months of age.