7.
Male and female Wistar rats were given an initiating i.p. injectionof diethylnitrosamine (DEN; 200 mg/kg body wt). Two weeks laterthe rats were given a diet containing 0.02% (w/w) 2-acetylaminofluorene(2-AAF) for 2 weeks. In the middle of the 2-AAF treatment a70% partial hepatectomy (PH) was performed. In order to identifythe pituitary hormone responsible for the previously observedsex difference (male > female) in and influence of ectopicpituitary grafts on focal growth during 2-AAF/PH selection ofenzyme-altered foci, male rats were treated with a continuousinfusion of bovine growth hormone (bGH; 6
µg/h) or ovineprolactin (oPrl; 6 µg/h) by way of osmotic minipumps.Hormonal treatment was started 1 week after initiation and wasfinished 1 week after the 2-AAF selection period. All rats werekilled 6 weeks after initiation and liver sections were stainedfor -ghitamyttransferase. The number of foci/cm
2 as well asthe area per focus and area ratio (mm
2 foci/cm
2 liver section)were calculated. Whereas no significant differences in the numberof foci /cm
2 were observed between the different groups of rats,bGH treatment of male rats decreased both the area/focus andthe area ratio down to the female level. No significant effectswere seen following oPrl administration when compared with controlmales.
In vitro studies of subcellular preparations from theliver lobes obtained at PH showed that the sexually differentiated
N-hydroxy-2-AAF sulfotransferase activity (male > female)in male rats was feminized, i.e. decreased, bybGH administration, but not by infusion of oPrl. The presentinvestigation strengthens the view of growth hormone as an importantdeterminant of sex differences in chemical carcinogenesis inrat liver, possibly via an influence on carcinogen metabolism.
相似文献