Huang S N, Chisari F V
Department of Pathology, Sunnybrook Health Science Centre, University of Toronto, Canada.
Hepatology. 1995 Mar;21(3):620-6.
Hepatocyte turnover rates were studied in two lineages of transgenic mice that overproduce the hepatitis B virus (HBV) large envelope protein and retain filamentous hepatitis B surface antigen (HBsAg) particles in the endoplasmic reticulum, resulting in the formation of ground glass hepatocytes. The high producer lineage (50-4) develops a necroinflammatory liver disease that progresses to hepatocellular carcinoma (HCC), whereas the low producer lineage (107-5) displays no histopathologic changes other than ground glass hepatocytes. Bromodeoxyuridine (BrdU)-labeling studies of S-phase hepatocytes provide quantitative evidence for a strong, sustained proliferative response in the hepatocytes in lineage 50-4 that occurs after the onset of hepatocellular injury but long before the development of liver cell tumors. In contrast, the level of hepatocellular proliferation in lineage 107-5 is the same as nontransgenic controls. The findings support the concept that sustained hepatocellular proliferation plays an important role in the development of hepatocellular carcinoma (HCC).
在两个转基因小鼠品系中研究了肝细胞更新率，这两个品系过量产生乙肝病毒（HBV）大包膜蛋白，并在内质网中保留丝状乙肝表面抗原（HBsAg）颗粒，导致形成毛玻璃样肝细胞。高表达品系（50 - 4）发展为坏死性炎症性肝病，并进展为肝细胞癌（HCC），而低表达品系（107 - 5）除毛玻璃样肝细胞外无其他组织病理学变化。对S期肝细胞进行溴脱氧尿苷（BrdU）标记研究，为50 - 4品系肝细胞在肝细胞损伤发生后但在肝细胞肿瘤形成之前很久就出现的强烈、持续增殖反应提供了定量证据。相比之下，107 - 5品系肝细胞增殖水平与非转基因对照相同。这些发现支持了持续肝细胞增殖在肝细胞癌（HCC）发生中起重要作用这一概念。
