SUPPRESSIVE EFFECT OF ESTROGEN ON HEPATOCELLULAR TUMORIGENESIS INDUCED IN MICE BY 3-METHYL-4-DIMETHYLAMINOAZOBENZENE

Treatment of female C57BL/6 x DS-F1 mice with 3'-methyl-4-dimethylamin oazobenzene (3'-Me-DAB) neonatally resulted in the development of hepa tocellular adenomatous nodules. Ovariectomy at 1 month of age greatly hastened the time of appearance of these nodules and significantly inc reased their incidence. The incidence of adenomatous nodules in female s 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 estra diol-17beta (E2 pellet) at 1 month of age (at the time of ovariectomy) . The incidence of adenomatous nodules at 12 months of age was not dec reased significantly when the implanted E2 pellet was removed at 4 or 6 months of age, but was decreased significantly when it was removed a t 8 or 10 months of age. Implantation of E2 pellets into ovariectomize d females at 4 and 6 months of age decreased the incidence of adenomat ous nodules as effectively as their implantation at 1 month of age. Th e implantation of E2 pellets into ovariectomized females at 8 or 10 mo nths 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, es trogen suppresses the development of hepatocellular tumors induced by 3'-Me-DAB, exerting its effect from about 6 months of age.