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ABSTRACT The rat hepatocytes were immortalized using a temperature-sensitive mutant of SV40 large T antigen (tsT) to develop as a possible substitute for primary hepatocytes. Four rat
hepatocyte lines that have been developed and maintained more than passage 50, were characterized for their cellular morphology, T antigen and p53 expression, chromosomes, liver-specific
differentiation, telomerase activity and anchorage independent growth. All of four cell lines showed a typical epithelial cell morphology, but the population-doubling time became short with
passage: 18 to 60%. T antigen expression was increased with passage about 3 to 65 times at permissive temperature but decreased significantly at non-permissive temperature. The expression
level of p53 unchanged during passages was also decreased at non-permissive temperature. The distribution of chromosome number changed somewhat with passage. The production levels of albumin
and urea in four cell lines were 2.4 to 13.0% and 7.5 to 19.9% of those produced in primary hepatocytes, respectively and were decreased to an undetectable level with passage. Telomerase
activity was increased 10 fold following immortalization of cells, but anchorage independent growth of cells did not develop. These results indicate that conditionally immortalized
hepatocytes become dedifferentiated with in vitro passage, which may be caused by marked chromosomal damages that occur with compulsive and continuous replications by the increment of T
antigen content with passage and its sequential inhibition of p53 function. SIMILAR CONTENT BEING VIEWED BY OTHERS HUMAN CELL TRANSFORMATION BY COMBINED LINEAGE CONVERSION AND ONCOGENE
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ATRESIA WITH CDK4R24C, CYCLIN D1, AND TERT FOR CYTOCHROME P450 INDUCTION TESTING Article Open access 15 October 2020 ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of
Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea Byung-Ho Kim Authors * Byung-Ho Kim View author publications You can also search for this author inPubMed Google
Scholar * Se-Ra Sung View author publications You can also search for this author inPubMed Google Scholar * Eun-Hee Choi View author publications You can also search for this author inPubMed
Google Scholar * Young-Il Kim View author publications You can also search for this author inPubMed Google Scholar * Kyeong-Jin Kim View author publications You can also search for this
author inPubMed Google Scholar * Seok-Ho Dong View author publications You can also search for this author inPubMed Google Scholar * Hyo-Jong Kim View author publications You can also search
for this author inPubMed Google Scholar * Young-Woon Chang View author publications You can also search for this author inPubMed Google Scholar * Joung-Il Lee View author publications You
can also search for this author inPubMed Google Scholar * Rin Chang View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS This is an
Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kim, BH., Sung,
SR., Choi, EH. _et al._ Dedifferentiation of conditionally immortalized hepatocytes with long-term in vitro passage. _Exp Mol Med_ 32, 29–37 (2000). https://doi.org/10.1038/emm.2000.6
Download citation * Published: 01 March 2000 * Issue Date: 01 March 2000 * DOI: https://doi.org/10.1038/emm.2000.6 SHARE THIS ARTICLE Anyone you share the following link with will be able to
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initiative KEYWORDS * chromosome * conditional immortalization * liverspecific differentiation * Rat hepatocytes * temperature-sensitive SV40 large T antigen * telomerase