Sexual differences in the expression of gamma-glutamyl transpeptidase during 5,9-dimethyldibenzo[c,g]carbazole-induced hepatocarcinogenesis in mice.

5,9-Dimethyl-7H-dibenzo[c,g]carbazole (5,9-diMeDBC) is an organ-specific carcinogen for mouse liver. It induces malignant hepatomas in 100% of XVIInc/Z and C57BL mice with a cumulative dose of only 12 mumol administered subcutaneously. Large sex-related differences in sensitivity towards this carcinogen were observed: entire males were much less sensitive than females. Castration of males nearly completely restored the sensitivity observed for females. The kinetics of appearance of gamma-glutamyl transpeptidase (gamma GT)-positive foci was enhanced in females and castrated males and was correlated with the tumour outbreak. On the contrary the expression of gamma GT in males was very reduced. The sex-dependent sensitivity seems to be regulated by a complex interplay of endogenous factors.