Hepatocarcinogenesis (Z#2)/mutagenesis during initiation stage
| Autor: | W. Stephen Nichols, Joseph A. Sorge, Jay M. Short, Mark J. Dycaico, Victoria J Edmond, Stephen A. Geller |
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| Rok vydání: | 1998 |
| Předmět: |
Genetically modified mouse
Health Toxicology and Mutagenesis Transgene Genetic Vectors Mutant Mutagenesis (molecular biology technique) Mice Transgenic Biology Lac repressor medicine.disease_cause Models Biological Mice Liver Neoplasms Experimental Bacterial Proteins Shuttle vector Lac Repressors Genetics medicine Animals Humans Molecular Biology Mutation Escherichia coli Proteins Molecular biology Repressor Proteins carbohydrates (lipids) alpha 1-Antitrypsin bacteria Carcinogenesis |
| Zdroj: | Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 398:143-149 |
| ISSN: | 0027-5107 |
| DOI: | 10.1016/s0027-5107(97)00204-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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