RRC ID 63345
著者 Lim PL, Tan W, Latchoumycandane C, Mok WC, Khoo YM, Lee HS, Sattabongkot J, Beerheide W, Lim SG, Tan TM, Boelsterli UA.
タイトル Molecular and functional characterization of drug-metabolizing enzymes and transporter expression in the novel spontaneously immortalized human hepatocyte line HC-04.
ジャーナル Toxicol In Vitro
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.
巻・号 21(8)
ページ 1390-401
公開日 2007-12-1
DOI 10.1016/j.tiv.2007.05.003
PII S0887-2333(07)00156-7
PMID 17590308
MeSH Acetaminophen / metabolism Analgesics, Non-Narcotic / metabolism Anti-Inflammatory Agents, Non-Steroidal / metabolism Antifibrinolytic Agents / metabolism Biomarkers Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Line Cytochrome P-450 Enzyme System / genetics Cytochrome P-450 Enzyme System / metabolism* Diclofenac / metabolism Gene Expression Profiling* Gene Expression Regulation* Hepatocytes / metabolism* Humans Vitamin K 3 / metabolism
IF 2.959
リソース情報
ヒト・動物細胞 HuH-7(RCB1366)