Blanck A, Hansson T, Eriksson L C, Gustafsson J A
Carcinogenesis. 1984 Oct;5(10):1257-62. doi: 10.1093/carcin/5.10.1257.
The resistant hepatocyte model was used to investigate the influence of pituitary factors on the early events of chemical carcinogenesis in rat liver. Diethylnitrosamine (DEN), 200 mg/kg body weight, was used as an initiator of enzyme altered foci. Two weeks after initiation the rats were placed on a 0.02% (w/w) 2-acetylaminofluorene (2-AAF) diet for two weeks. Partial hepatectomy (70%) was performed three weeks after initiation. The rats were killed four to six weeks after DEN initiation. Sex differences in area/foci as well as in area ratio (mm2 foci/cm2 liver section) were found in liver sections from sexually mature male and female rats (male greater than female) of both the Sprague-Dawley and Wistar strains. Ectopic pituitary grafts (PG:s) implanted under the kidney capsule of male Wistar rats one week before DEN initiation and removed by unilateral nephrectomy one week after initiation did not influence the number or area of enzyme altered foci as compared with sham operated male rats. On the other hand, PG:s implanted one week before 2-AAF selection in male Wistar rats and allowed to remain until the rats were killed two weeks after the 2-AAF selection period, decreased the area ratio to a level close to that of sham operated female rats, whereas no effect on the number of enzyme altered foci was found. The results suggest that the hypothalamo-pituitary axis may be involved in the regulation of early stages of liver carcinogenesis.
采用抗药肝细胞模型研究垂体因子对大鼠肝脏化学致癌早期事件的影响。以200mg/kg体重的二乙基亚硝胺（DEN）作为酶改变灶的启动剂。启动后两周，将大鼠置于含0.02%（w/w）2-乙酰氨基芴（2-AAF）的饲料中喂养两周。启动后三周进行部分肝切除术（70%）。在DEN启动后四至六周处死大鼠。在斯普拉格-道利和Wistar品系性成熟的雄性和雌性大鼠（雄性大于雌性）的肝切片中，发现了面积/灶以及面积比（mm2灶/cm2肝切片）的性别差异。在DEN启动前一周将异位垂体移植（PG）植入雄性Wistar大鼠的肾被膜下，并在启动后一周通过单侧肾切除术取出，与假手术雄性大鼠相比，PG对酶改变灶的数量或面积没有影响。另一方面，在雄性Wistar大鼠选择2-AAF前一周植入PG，并使其保留至2-AAF选择期后两周处死大鼠，结果使面积比降至接近假手术雌性大鼠的水平，而对酶改变灶的数量没有影响。结果表明，下丘脑-垂体轴可能参与肝脏致癌早期阶段的调节。
