Comparative study of diethylnitrosamine-initiated two-stage hepatocarcinogenesis in C3H, C57BL and BALB mice promoted by various hepatopromoters.
Comparative study of diethylnitrosamine-initiated two-stage hepatocarcinogenesis in C3H, C57BL and BALB mice promoted by various hepatopromoters.
复制标题
不同促肝剂促进C3H、C57BL和BALB小鼠二乙基亚硝胺引发的两阶段肝癌的比较研究。
作者：
Gang‐hong Lee;K. Nomura;T. Kitagawa
本文比较了二乙基亚硝胺（DEN）对C_3H/HeN（C_3H）、C_57BL/6 N（C_57）和BALB/cA（BALB）小鼠肝细胞酶变岛（EAI）的诱导作用及其对不同类型促肝剂的反应性。雄性小鼠在6周龄时部分肝切除后腹腔注射DEN（20微克/克体重），然后喂食基础饮食或含苯巴比妥（PB）的饮食（500 p. p.m.），氯贝特（CF）（1000 p. p.m.）或乙炔雌二醇（EE）（10 p. p.m.）。在第20周处死小鼠后，利用体视学方法评估EAI的数量和大小分布。在接受DEN但没有启动子的组中，C3 H小鼠的病变数量和平均大小远大于其他品系。在PB的促生长压力下，C3 H和BALB小鼠的EAI生长明显加快，而C57小鼠的EAI生长则略有加快。有趣的是，在BALB中，尽管它们对PB具有良好的敏感性，但EAI的数量远少于C3 H，这表明BALB对DEN的启动过程是难治的。CF的促进作用仅在C3 H菌株和EE中得到证实，因为所用剂量抑制了所有菌株中EAI的发展。因此，实验数据表明，在两个阶段的肝癌发生在不同的遗传背景的小鼠之间的品系差异可能存在，无论是在启动或促进，或在这两个过程。
The comparative inducibility of enzyme-altered islands (EAIs) by diethylnitrosamine (DEN) and their responsiveness to hepatopromoters belonging to different classes were studied in C3H/HeN (C3H), C57BL/6N (C57) and BALB/cA (BALB) mice. Male mice were given an i.p. injection of DEN (20 micrograms/g body weight) after partial hepatectomy at 6 weeks of age and then fed either basal diet or diet containing phenobarbital (PB) (500 p.p.m.), clofibrate (CF) (1000 p.p.m.) or ethynyl estradiol (EE) (10 p.p.m.). The numbers and size distribution of EAIs were assessed after the mice were killed at week 20, utilizing stereological methods. In the groups receiving DEN but no promoter, the number and mean size of the lesions were far larger in the C3H mice than in the other strains. Under the promoting pressure of PB, the growth of EAIs in C3H and BALB were accelerated remarkably, but those of C57 mice only slightly. Interestingly, in BALB the number of EAIs was much fewer than those of C3H in spite of their good sensitivity to PB, suggesting that BALB was refractory to the initiation process by DEN. A promoting effect for CF could only be demonstrated for the C3H strain and EE as the dose used inhibited the development of EAIs in all the strains. The experimental data thus indicate that interstrain differences in two-stage hepatocarcinogenesis among mice with different genetical backgrounds may exist, either in initiation or promotion, or in both processes.