Pituitary grafts modify sex differences in liver tumor formation in the rat following initiation with diethylnitrosamine and different promotion regimens

We previously reported on sex differences in chemical hepatocarcinogenesisstudied in the resistant hepatocyte model and on the effectsof implantation of ectopic pituitary grafts into male rats onthe early stages of liver carcinogenesis. Marked sex differenceswere found in the area ratio of enzyme-altered foci (mm² foci/cm²liver section) in sexually mature male and female Wistar rats(>). Pituitary grafts implanted one week before 2-acetylaminofluoreneselection in male rats decreased the area ratio to a level nearthat of sham operated females. The present study was performedin order to investigate the relevance of the results in theshort-term experiment in terms of hepatoma formation. To studythe importance of 2-acetylaminofluorene selection as a determinantof the observed sex differences an experiment was also performedusing the Pitot-model, where male and female rats were initiatedwith diethylnitrosamine and promotion was performed with phenobarbital.The long-term experiments in the resistant hepatocyte modelshowed that male rats develop hepatomas earlier than femalerats and also showed a tendency towards a prolonged latencytime in male rats bearing pituitary grafts. A good correspondencewas thus achieved between the short-term and the long-term experiments. The rats treated according to the -Pitot-model did not develophepatomas within the experimental period. Of the rats killedat 13 months, three (out of five) male and five (out of five)female rats had hepatocyte nodules whereas, at 19 months two(out of six) male and five (out of six) female rats had developedsuch lesions in this model. We therefore con-dude that 2-acetylaminofluoreneis the factor responsible for the sex differences in the resistanthepatocyte model and that the hypothalamo-pituitary influenceduring 2-acetylaminofluorene selection is an important modifierof the carcino-genetic process.