Please use this identifier to cite or link to this item:
|Title:||Molecular and functional characterization of drug-metabolizing enzymes and transporter expression in the novel spontaneously immortalized human hepatocyte line HC-04|
|Keywords:||Drug toxicity in vitro|
Immortalized human hepatocytes
|Citation:||Lim, P.L.K., Latchoumycandane, C., Khoo, Y.M., Lee, H.S., Boelsterli, U.A., Tan, W., Tan, T.M.C., Mok, W.C., Lim, S.G., Sattabongkot, J., Beerheide, W. (2007). Molecular and functional characterization of drug-metabolizing enzymes and transporter expression in the novel spontaneously immortalized human hepatocyte line HC-04. Toxicology in Vitro 21 (8) : 1390-1401. ScholarBank@NUS Repository.|
|Abstract:||In toxicological research, immortalized human hepatocytes provide a useful alternative to primary hepatocytes because interindividual variability in the expression of drug-metabolizing enzymes and drug transporters can largely be eliminated. However, it is essential that the cell line retain the original phenotype. The purpose of this study was to characterize a novel spontaneously immortalized human hepatocyte cell line, HC-04, with respect to the transcript and functional protein expression profile for the major drug-metabolizing enzymes and transmembrane transporters. HC-04 cells retained hepatocyte-specific function including albumin production and ornithine transcarbamoylase and glucose-6-phosphatase activity. Most of the major CYP forms were expressed at basal levels and responsive to inducing agents. In particular, CYP3A4 was expressed abundantly, and HC-04 cells were able to metabolize the CYP3A4 probe, midazolam, at a rate similar to primary human hepatocytes. Furthermore, the major human sulfotransferase and UDP-glucuronosyltransferase forms, as well as members of the ABC and SLC transporter superfamilies, nuclear receptors, and hepatic transcription factors were also expressed. HC-04 cells readily responded to standard hepatotoxicants that are dependent on CYP-mediated bioactivation, while another, tumor-derived cell line remained refractory to the drug challenge. Collectively, HC-04 cells provide a reliable, stable, and reproducible model for biomechanistic studies in drug toxicology. © 2007 Elsevier Ltd. All rights reserved.|
|Source Title:||Toxicology in Vitro|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Feb 26, 2018
WEB OF SCIENCETM
checked on Apr 30, 2018
checked on Aug 4, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.