Fischer G
Virchows Arch B Cell Pathol Incl Mol Pathol. 1986;51(5):443-60. doi: 10.1007/BF02899051.
Preneoplastic liver lesions were produced in female Wistar rats by low doses of aflatoxin B1 (Model 1: administration of 37.5 micrograms/kg 12 and 24 h after partial hepatectomy; Model 2: continuous application of 3.5 micrograms/kg in tap water daily for 28 days with partial hepatectomy after 14 days. The animals then received sodium phenobarbital, 0.1% in tap water, for 180 to 400 days). In both models numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected enzyme histochemically by their negative ATPase and positive gamma-glutamyltranspeptidase reactions. Immunohistochemically these lesions were also UDP-glucuronyltransferase positive. Increased UDP-glucuronyltransferase adds to permanent alterations of a number of drug metabolizing enzymes observed in a variety of different tumor models. These alterations are responsible for the toxin-resistant phenotype (Faber 1984b). Increased gamma-glutamyltranspeptidase was detected both enzyme histochemically and immunohistochemically; whereas gamma-glutamyltranspeptidase activity was present in both AHF/HN and in periportal areas by enzyme histochemistry, the immunohistochemical method selectively stained gamma-glutamyltranspeptidase in AHF and HN. Immunohistochemically detectable UDP-glucuronyltransferase and gamma-glutamyltranspeptidase are markers of putative precancerous liver lesions which may be useful in the analysis of the prestages of liver carcinogenesis.
通过低剂量黄曲霉毒素B1在雌性Wistar大鼠中诱导癌前肝损伤（模型1：在部分肝切除术后12小时和24小时给予37.5微克/千克；模型2：在自来水中每天持续给予3.5微克/千克，共28天，14天后进行部分肝切除。然后给动物饮用含0.1%苯巴比妥钠的自来水，持续180至400天）。在这两种模型中，通过酶组织化学检测到大量改变的肝灶（AHF）和增生性结节（HN），其ATP酶反应阴性，γ-谷氨酰转肽酶反应阳性。免疫组织化学检测显示这些病变UDP-葡萄糖醛酸基转移酶也呈阳性。UDP-葡萄糖醛酸基转移酶增加，这是在多种不同肿瘤模型中观察到的许多药物代谢酶永久性改变的原因之一。这些改变导致了抗毒素表型（法伯，1984b）。通过酶组织化学和免疫组织化学都检测到γ-谷氨酰转肽酶增加；酶组织化学显示γ-谷氨酰转肽酶活性在AHF/HN和门静脉周围区域均有，但免疫组织化学方法选择性地在AHF和HN中对γ-谷氨酰转肽酶进行染色。免疫组织化学可检测到的UDP-葡萄糖醛酸基转移酶和γ-谷氨酰转肽酶是假定的癌前肝损伤标志物，可能有助于分析肝癌发生的前期阶段。
