Ras-transduced Diethylnitrosamine-treated Hepatocytes Develop into Cancers of Mixed Phenotype in Vivo

摘要: The cell of origin hepatocellular carcinoma (HCC) is controversial. A method for marking cells different lineages in vivo and then determining their carcinogenic potential should resolve this issue. retroviral vector expressing activated ras β- gal genes ( Ras-gal ) was transferred into adult rat hepatocytes , some animals were treated with diethylnitrosamine (DEN). Bile ductule the putative stem liver (the oval cells) did not appear to be transduced by method. At 1 month after transfer, 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside staining performed on livers determine blue cluster size. Eight % clusters -transduced, DEN-treated contained at least twice as many largest DEN-untreated rats, demonstrating that they had acquired markedly abnormal growth properties. When containing β-gal without (Gal-509) 2.5% present Gal-509-transduced, animals. Thus, p21- may increase percentage acquire mutations response DEN, or it behave synergistically other replication rate cells. Occasional foci rats extramedullary hematopoiesis. Forty developed unifocal HCC, mixed HCC/cholangiocarcinoma (CC), CC 3–6 months transduction, suggesting can develop HCC if sufficient genetic alterations occur.