title: In vivo cell lineage analysis during chemical hepatocarcinogenesis using retroviral-mediated gene transfer.
abstract: We have studied the proliferation of cells in two models of chemical hepatocarcinogenesis. The cells were genetically labeled in vivo using retrovirally mediated transfer of the Escherichia coli beta-galactosidase marker gene coupled to a nuclear localization signal (nls-lacZ gene). In the first carcinogenic model, rats were fed a choline-deficient diet containing 2-acetylaminofluorene, and their livers were perfused with recombinant retrovirus at the onset of oval cell proliferation. The second model was based on the administration of diethylnitrosamine coupled with a partial hepatectomy and is thought to induce cancer with no involvement of oval cells. Analysis of beta-galactosidase expression in the liver at various times after gene transfer revealed the presence of large clusters of positive cells in both models. Moreover, the beta-galactosidase-positive cells displayed morphologic, antigenic, and enzymatic profiles consistent with a hepatocyte phenotype. Our results, therefore, provide evidence for a strikingly similar clonal proliferation of apparently normal hepatocytes during the course of 2-acetylaminofluorene- as well as diethylnitrosamine-induced liver carcinogenesis.
authors.affiliation: INSERM U370, Paris, France.
authors.forename: M P
authors.initials: MP
authors.lastname: Bralet
authors.forename: D
authors.initials: D
authors.lastname: Calise
authors.forename: C
authors.initials: C
authors.lastname: Brechot
authors.forename: N
authors.initials: N
authors.lastname: Ferry
mesh_terms: D015073:2-Acetylaminofluorene / Q000633:toxicity; D000818:Animals; D014408:Biomarkers, Tumor; D002273:Carcinogens / Q000633:toxicity; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage; D004052:Diethylnitrosamine / Q000633:toxicity; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012190:Retroviridae / Q000235:genetics*; D013997:Time Factors; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D001616:beta-Galactosidase