Roles of ovaries and testes in hepatocellular tumorigenesis induced in mice by 3′-methyl-4-dimethylaminoazobenzene



The roles of gonads in tumorigenesis induced in mouse liver by 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB) were investigated. C57BL/6 × DS-F1 mice which were 10, 12, 14, 16 and 18 days old were treated i.p. with 3′-Me-DAB. Nodular lesions induced in the liver were classified into adenomatous nodules and hepatocellular carcinomas. Adenomatous nodules were composed of a mixture of eosinophilic, basophilic, vacuolated and foamy hepatocytes in various proportions and compressed the adjacent parenchyma. These adenomatous nodules were of monoclonal origin. Carcinomas had a trabecular structure. The incidence, numbers per mouse and areas of adenomatous nodules and carcinomas in male and female mice aged 16-64 weeks were compared. Adenomatous nodules were first detected in males and females aged 24 and 52 weeks, respectively, and their incidences were much higher in males than in females of the same age. The number of adenomatous nodules per mouse and their size were also higher in males. The first carcinoma was found in a 52-week-old male, but no carcinomas were found in females even at 64 weeks of age. The effects of castration 23 days after birth on the appearance of nodular lesions in the livers of 32- to 64-week-old mice were examined. Castration of males did not affect the incidence of adenomatous nodules, but reduced the incidence of carcinomas. It also decreased the number of adenomatous nodules per mouse. Castration of females reduced the time before appearance of adenomatous nodules and increased their incidence, number per mouse, and area. A carcinoma appeared in a 64-week-old castrated female, but no similar lesion was found in intact females of the same age. These results indicate that tumorigenesis induced in mouse liver by 3′-Me-DAB is enhanced by the testes and suppressed by the ovaries.