大鼠再生肝对二乙基亚硝胺启动作用的敏感性

目的比较再生肝和正常肝对二乙基亚硝胺（ＤＥＮ）启动作用的敏感性。方法以２／３肝叶切除后８周末的大鼠为实验组,正常大鼠为对照组,作如下比较：肝重、常规组织学检查及３Ｈ－ＴｄＲ掺入试验;用修改的Ｓｏｌｔ－Ｆａｒｂｅｒ模型,通过对ＧＧＴ阳性癌前病灶的体视学测量,观察肝脏对ＤＥＮ的启动效应;在体内和体外（无血清原代培养肝细胞）经ＤＥＮ攻击后,以核酸原位缺口标记方法观察肝细胞ＤＮＡ的损伤程度。结果２／３肝叶切除后８周末的实验组肝脏的修复过程已完成,未见肝细胞继续增生的表现;经ＤＥＮ攻击后,实验组肝癌前病灶在数密度和体积密度上都显著高于对照组;无论在体内或体外接受ＤＥＮ攻击后,实验组肝细胞ＤＮＡ的损伤程度都显著大于对照组。结论即使再生过程已经完成,再生肝仍比正常肝具有较高的致癌敏感性,这与再生肝肝细胞在ＤＥＮ攻击后其ＤＮＡ损伤较重相关。

The sensitivity of carcinogenic initiation effect of regenerated liver induced by diethylnitrosamine in rats

Objective To compare the sensitivity of carcinogenic initiation effect of regenerated liver with normal liver induced by diethylnitrosamine (DEN) in rats. Methods Experimental group was composed of rats that had 2/3 of their liver excised 8 weeks previously, normal rats were used as controls to study: (1) weight of their livers, conventional histological examination and 3H TdR incorporation test; (2) a modified Solt Farber carcinogenesis scheme was applied in order to detect the degree of carcinogenic initiation effect by stereologic study of GGT positive preneoplastic liver cell foci; (3) damage of DNA in hepatocytes were detected by in situ nick translation test after DEN treatment both in vivo and in primary cultured liver cells. Results (1) the regenerative process in liver was completed by the end of the 8th post operative week and no proliferation of hepatocytes was detected. (2) both the number and volume density of GGT positive foci in the experimental group were higher than those in control group. (3) DNA damage in hepatocytes of experimental group were more severe than in the control group. Conclusion Even after the regeneration process was completed, the regenerated liver still possessed higher sensitivity to carcinogenic initiation effect than normal liver, this sensitivty was related with the severity of DNA damage in hepatocytes of the regenerated liver after DEN attack.