ArticleBMC biotechnology2004
Cell-based assay for the detection of chemically induced cellular stress by immortalized untransformed transgenic hepatocytes.
Article in BMC biotechnology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 15 citations in OpenAlex.
- Brain organoids as a model system for human neurodevelopment and disease.Seminars in cell & developmental biology · 2019Review
- YAP integrates the regulatory Snail/HNF4α circuitry controlling epithelial/hepatocyte differentiation.Cell death & disease · 2019Article
- Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes.Stem cells international · 2016Article
- TGFbeta Induces Binucleation/Polyploidization in Hepatocytes through a Src-Dependent Cytokinesis Failure.PloS one · 2016Article
- Glutathione-S-transferase enhances proliferation-migration and protects against shikonin-induced cell death in breast cancer cells.The Kaohsiung journal of medical sciences · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrimary hepatocytes, one of the most widely used cell types for toxicological studies, have a very limited life span and must be freshly derived from mice or even humans. Attempts to use stable cell lines maintaining the enzymatic pattern of liver cells have been so far unsatisfactory. Stress proteins (heat shock proteins, HSPs) have been proposed as general markers of cellular injury and their use for environmental monitoring has been suggested. The aim of this work is to develop a bi-transgenic hepatocyte cell line in order to evaluate the ability of various organic and inorganic chemicals to induce the expression of the HSP70 driven reporter gene. We previously described transgenic mice (Hsp70/hGH) secreting high levels of human Growth Hormone (hGH) following exposure to toxic compounds in vivo and in vitro in primary cultures derived from different organs. In addition, we also reported another transgenic model (AT/cytoMet) allowing the reproducible immortalization of untransformed hepatocytes retaining in vitro complex liver functions.
resultsThe transgenic mouse line Hsp70/hGH was crossed with the AT/cytoMet transgenic strain permitting the reproducible immortalization of untransformed hepatocytes. From double transgenic animals we derived several stable hepatic cell lines (MMH-GH) which showed a highly-differentiated phenotype as judged from the retention of epithelial cell polarity and the profile of gene expression, including hepatocyte-enriched transcription factors and detoxifying enzymes. In these cell lines, stresses induced by exposure to inorganic [Sodium Arsenite (NaAsO2) and Cadmium Chloride (CdCl2)], and organic [Benzo(a)Pyrene (BaP), PentaChloroPhenol (PCP), TetraChloroHydroQuinone (TCHQ), 1-Chloro-2,4-DiNitro-Benzene (CDNB)] compounds, specifically induced hGH release in the culture medium.
conclusionsMMH-GH, an innovative model to evaluate the toxic potential of chemical and physical xenobiotics, provides a simple biological system that may reduce the need for animal experimentation and/or continuously deriving fresh hepatocytes.
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