SEX-DIFFERENTIATED AND GROWTH-HORMONE-REGULATED MITOINHIBITION IN RAT-LIVER DURING TREATMENT WITH 2-ACETYLAMINOFLUORENE AND PARTIAL-HEPATECTOMY IN THE RESISTANT HEPATOCYTE MODEL

被引:19
作者
BLANCK, A
ERIKSSON, LC
GUSTAFSSON, JA
HALLSTROM, IP
机构
[1] UNIV STOCKHOLM,DEPT TOXICOL GENET,S-10691 STOCKHOLM,SWEDEN
[2] HUDDINGE UNIV HOSP,KAROLINSKA INST,DEPT PATHOL,S-14186 HUDDINGE,SWEDEN
关键词
D O I
10.1093/carcin/12.7.1259
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The previously observed sex difference in the growth rate of enzyme-altered foci (male > female) in rats treated according to the resistant hepatocyte model (RH model) occurs during selection/promotion of diethylnitrosamine-initiated cells with dietary 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH). The secretory pattern of growth hormone (GH) is sex dependent in the adult rat and is a major determinant for sex-differentiated liver functions. In the present study the capacity for liver regeneration following PH in the RH model was studied in rats of both sexes, in castrated males and in males receiving GH infusion, both treatments leading to a feminine pattern of GH secretion. Mitoinhibition during treatment with 2-AAF was shown to be more pronounced in liver from male than from female rats, both in initiated and non-initiated animals. Castration of male rats and continuous infusion of GH to males during the selection period, previously shown to decrease the focal growth rate towards that in female rats, 'feminized' also the degree of mitoinhibition. Autoradiography of sections from animals receiving continuous infusion of [H-3]thymidine for 1 week, starting at the time of PH, demonstrated a lower labeling index in surrounding liver from male rats treated in the RH model than in surrounding liver from female rats. Males treated with continuous infusion of human GH during 2-AAF/PH treatment had an intermediary labeling index in the surrounding tissue. No differences in labeling index in enzyme-altered foci was observed between males, females or males plus hGH. These findings support the concept that sex-differentiated promotion in the RH model is exerted by selective mitoinhibition and that this feature is regulated by GH.
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页码:1259 / 1264
页数:6
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