title: Hepatocarcinogenesis (Z#2)/mutagenesis during initiation stage.
abstract: Previously, we developed a model for high incidence, endogenously generated hepatocellular carcinoma (HCC), the human alpha-1-antitrypsin (alpha1AT) Z gene transgenic mouse (Z#2). We now examine the potential utility of a model for endogenous carcinogenesis utilizing the Z#2 mouse also transgenic for the lacI gene, a convenient target for in vivo mutagenesis studies. We crossed the Z#2 line and mice transgenic for lambda/lacI shuttle vector (Big Blue), for determination of lacI mutant frequency during initiation of endogenous carcinogenesis. Five month old double transgenic mice (Z#2+/lacI+) successfully displayed: (1) the expected post-inflammatory stage of Z#2 carcinogenesis; and (2) hepatic lacI mutants measured at frequencies (10(-5)-10(-4)) useful to mutagenesis studies. In this study, hepatic lacI mutation frequencies in Z#2 transgenic mice appeared to be only slightly increased (< 2x) when compared to age matched negative controls. In the future, it may be important to reconcile possibly limited lacI mutagenesis at the time of initiation and demonstrated high incidence of hepatocarcinogenesis.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. nicholsws@csmc.edu
authors.forename: W S
authors.initials: WS
authors.lastname: Nichols
authors.forename: S A
authors.initials: SA
authors.lastname: Geller
authors.forename: V J
authors.initials: VJ
authors.lastname: Edmond
authors.forename: M J
authors.initials: MJ
authors.lastname: Dycaico
authors.forename: J A
authors.initials: JA
authors.lastname: Sorge
authors.forename: J M
authors.initials: JM
authors.lastname: Short
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D029968:Escherichia coli Proteins; D005822:Genetic Vectors; D006801:Humans; D056968:Lac Repressors; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D012097:Repressor Proteins / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D012097:Repressor Proteins; D000515:alpha 1-Antitrypsin