Experimental studies on hepatocarcinogenesis of synthetic estrogen and progestogen with special reference to progression and biological characteristics of the developed hepatocellular carcinoma.

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Hepatocarcinogenesis was studied by oral administration of synthetic estrogen and progestogen (Pill) in female rats of Wistar strain aged 4 weeks, with special interest to progression and biological characteristics of the developed hepatocellular carcinoma. Under 18-month daily administration of ethynyl estradiol of 0.15mg and norethindrone acetate of 12mg dissolved in 1.0ml of olive oil through the gastric tube, all rats developed hyperplastic nodules and 21.3% of them was proved to have hepatocellular carcinoma at the end of 12th month. Thereafter, the incidence of hepatocellular carcinoma rapidly increased, showing 74.5% at the end of 18th month. More than 75% of the liver was occupied by hepatocellular carcinoma in 77.4% of tumor-bearing rats at the end of 18th month. Doubling times of these carcinomas were 139.5±127.1 days, and DNA histograms revealed aneuploidy and polyploidy, showing the proof of malignant potential. From the study of allotransplantation of this carcinoma to the subcapsular space of kidney, hormone administration to recipient rats was required to establish the transplantation, demonstrating a highly hormone dependent tumor.
社団法人日本肝臓学会の論文