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|Title:||Molecular and functional characterization of drug-metabolizing enzymes and transporter expression in the novel spontaneously immortalized human hepatocyte line HC-04||Authors:||Lim, P.L.K.
|Keywords:||Drug toxicity in vitro
Immortalized human hepatocytes
|Issue Date:||2007||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||URI:||http://scholarbank.nus.edu.sg/handle/10635/27430||ISSN:||08872333|
|Appears in Collections:||Staff Publications|
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