Tatematsu M, Mera Y, Inoue T, Satoh K, Sato K, Ito N
First Department of Pathology, Nagoya City University Medical School, Japan.
Carcinogenesis. 1988 Feb;9(2):215-20. doi: 10.1093/carcin/9.2.215.
Using immunohistochemical demonstration of glutathione S-transferase placental type (GST-P) and histochemical demonstration of gamma-glutamyltransferase (gamma-GT), the long-term development of preneoplastic and neoplastic lesions was followed in rats over a 50-week period. Rats were given a single i.p. injection of 200 mg/kg body weight of diethylnitrosamine (DEN), and then 2 weeks later were administered 0.02% 2-acetylaminofluorene (2-AAF) (group 1), 0.05% phenobarbital (PB) (group 2), 2.0% butylated hydroxyanisole (BHA) (group 3) or no supplement (group 4) in their diet for 6 weeks, all rats being subjected to partial hepatectomy at week 3. Hepatocellular proliferated lesions were classified as foci, nodules and hepatocellular carcinomas. Development of foci, nodules and hepatocellular carcinomas was enhanced strongly by 2-AAF and weakly by PB, and inhibited by BHA. Almost all foci and nodules were GST-P positive, although 5-10% of the GST-P-positive foci were gamma-GT negative. The areas of GST-P-positive foci and nodules increased with time in all groups. In contrast, while the areas of gamma-GT-positive lesions also increased with time in groups 2-4, they decreased from week 12 in group 1. As the percentage gamma-GT-positive area in GST-P-positive foci significantly decreased with time in all groups, the rate of phenotypic reversion of gamma-GT in foci in group 1 was revealed to be larger than the focus growing rate, whereas that in groups 2-4 was smaller. Gamma-GT-negative and GST-P-positive micro-nodules of altered morphology appeared within gamma-GT- and GST-P-positive nodules in later stages. All hepatocellular carcinomas found in this experiment consisted of GST-P-positive cells. In contrast, 37% (13/35) of the hepatocellular carcinomas were negative for gamma-GT. The results indicate GST-P to be the most accurate marker enzyme for detection of initiated cells during liver carcinogenesis and gamma-GT to be more appropriate for indicating changes of phenotypic expression in each lesion type.
运用谷胱甘肽S-转移酶胎盘型（GST-P）的免疫组化检测及γ-谷氨酰转移酶（γ-GT）的组织化学检测，在50周的时间里跟踪观察了大鼠癌前病变和肿瘤病变的长期发展情况。给大鼠腹腔注射一次200mg/kg体重的二乙基亚硝胺（DEN），然后在2周后，给第1组大鼠的饮食中添加0.02%的2-乙酰氨基芴（2-AAF），给第2组添加0.05%的苯巴比妥（PB），给第3组添加2.0%的叔丁基对羟基茴香醚（BHA），第4组不添加任何补充剂，持续6周，所有大鼠在第3周时接受部分肝切除术。肝细胞增殖性病变分为灶性病变、结节性病变和肝细胞癌。2-AAF强烈促进灶性病变、结节性病变和肝细胞癌的发展，PB作用较弱，BHA则起抑制作用。几乎所有的灶性病变和结节性病变GST-P均呈阳性，尽管5%-10%的GST-P阳性灶γ-GT呈阴性。所有组中GST-P阳性灶和结节的面积均随时间增加。相比之下，虽然第2-4组中γ-GT阳性病变的面积也随时间增加，但第1组从第12周起其面积减小。由于所有组中GST-P阳性灶内γ-GT阳性面积的百分比均随时间显著降低，结果显示第1组灶性病变中γ-GT的表型逆转率大于病灶生长率，而第2-4组则较小。后期在γ-GT和GST-P阳性结节内出现了形态改变的γ-GT阴性和GST-P阳性微结节。本实验中发现的所有肝细胞癌均由GST-P阳性细胞组成。相比之下，37%(13/35)的肝细胞癌γ-GT呈阴性。结果表明，GST-P是检测肝癌发生过程中起始细胞最准确 的标记酶，而γ-GT更适合于指示每种病变类型中表型表达的变化。
