On mechanisms of sex differences in chemical carcinogenesis: effects of implantation of ectopic pituitary grafts on the early stages of liver carcinogenesis in the rat

The resistant hepatocyte model was used to investigate the influenceof pituitary factors on the early events of chemical carcinogenesisin rat liver. Diethylnitrosamine (DEN), 200 mg/kg body weight,was used as an initiator of enzyme altered foci. Two weeks afterinitiation the rats were placed on a 0.02% (w/w) 2-acetylaminofluorene(2-AAF) diet for two weeks. Partial hepatectomy (70%) was performedthree weeks after initiation. The rats were killed four to sixweeks after DEN initiation. Sex differences in area/foci aswell as in area ratio (mm² foci/cm² liver section) were foundin liver sections from sexually mature male and female rats( > ) of both the Sprague-Dawley and Wistar strains. Ectopicpituitary grafts (PG: s) implanted under the kidney capsuleof male Wistar rats one week before DEN initiation and removedby unilateral nephrectomy one week after initiation did notinfluence the number or area of enzyme altered foci as comparedwith sham operated male rats. On the other hand, PG:s implantedone week before 2-AAF selection in male Wistar rats and allowedto remain until the rats were killed two weeks after the 2-AAFselection period, decreased the area ratio to a level closeto that of sham operated female rats, whereas no effect on thenumber of enzyme altered foci was found. The results suggestthat the hypothalamo-pitu-itary axis may be involved in theregulation of early stages of liver carcinogenesis.