![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
German Research Centre for Biotechnology, Organund Gewebekultur, Braunschweig, Germany (S.W., F.S.); and University of Tuebingen, Institute of Anatomy, Tuebingen, Germany (A.B.)
Cultures of primary hepatocytes and hepatoma cell line HepG2 are frequently used in in vitro models for human biotransformation studies. In this study, we characterized and compared the capacity of these model systems to indicate the presence of different classes of promutagens. Genotoxic sensitivity, enzyme activity, and gene expression were monitored in response to treatment with food promutagens benzo[a]pyrene, dimethylnitrosamine (DMN), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). DNA damage could be detected reliably with the comet assay in primary human hepatocytes, which were maintained in sandwich culture. All three promutagens caused DNA damage in primary cells, but in HepG2 no genotoxic effects of DMN and PhIP could be detected. We supposed that the lack of specific enzymes accounts for their inability to process these promutagens. Therefore, we quantified the expression of a broad range of genes coding for drug-metabolizing enzymes with real-time reverse transcription-polymerase chain reaction. The genes code for cytochromes P450 and, in addition, for a series of important phase II enzymes. The expression level of these genes in human hepatocytes was similar to those previously reported for human liver samples. On the other hand, expression levels in HepG2 differed significantly from that in human. Activity and expression, especially of phase I enzymes, were demonstrated to be extremely low in HepG2 cells. Up-regulation of specific genes by test substances was similar in both cell types. In conclusion, human hepatocytes are the preferred model for biotransformation in human liver, whereas HepG2 cells may be useful to study regulation of drug-metabolizing enzymes.
This article has been cited by other articles:
|
|
 |
|
  K. Monostory, J.-M. Pascussi, P. Szabo, M. Temesvari, K. Kohalmy, J. Acimovic, D. Kocjan, D. Kuzman, B. Wilzewski, R. Bernhardt, et al. Drug Interaction Potential of 2-((3,4-Dichlorophenethyl)(propyl)amino)-1-(pyridin-3-yl)ethanol (LK-935), the Novel Nonstatin-Type Cholesterol-Lowering Agent Drug Metab. Dispos., February 1, 2009; 37(2): 375 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mizuno, M. Katoh, H. Okumura, N. Nakagawa, T. Negishi, T. Hashizume, M. Nakajima, and T. Yokoi Metabolic Activation of Benzodiazepines by CYP3A4 Drug Metab. Dispos., February 1, 2009; 37(2): 345 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Seferovic, R. Ali, H. Kamei, S. Liu, J. M. Khosravi, S. Nazarian, V. K. M. Han, C. Duan, and M. B. Gupta Hypoxia and Leucine Deprivation Induce Human Insulin-Like Growth Factor Binding Protein-1 Hyperphosphorylation and Increase Its Biological Activity Endocrinology, January 1, 2009; 150(1): 220 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Ehnert, A. K. Nussler, A. Lehmann, and S. Dooley Blood Monocyte-Derived Neohepatocytes as in Vitro Test System for Drug Metabolism Drug Metab. Dispos., September 1, 2008; 36(9): 1922 - 1929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Harmsen, A. S. Koster, J. H. Beijnen, J. H. M. Schellens, and I. Meijerman Comparison of Two Immortalized Human Cell Lines to Study Nuclear Receptor-Mediated CYP3A4 Induction Drug Metab. Dispos., June 1, 2008; 36(6): 1166 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Josse, C. Aninat, D. Glaise, J. Dumont, V. Fessard, F. Morel, J.-M. Poul, C. Guguen-Guillouzo, and A. Guillouzo Long-Term Functional Stability of Human HepaRG Hepatocytes and Use for Chronic Toxicity and Genotoxicity Studies Drug Metab. Dispos., June 1, 2008; 36(6): 1111 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Dykens, J. D. Jamieson, L. D. Marroquin, S. Nadanaciva, J. J. Xu, M. C. Dunn, A. R. Smith, and Y. Will In Vitro Assessment of Mitochondrial Dysfunction and Cytotoxicity of Nefazodone, Trazodone, and Buspirone Toxicol. Sci., June 1, 2008; 103(2): 335 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Liguori, E. A.G. Blomme, and J. F. Waring Trovafloxacin-Induced Gene Expression Changes in Liver-Derived in Vitro Systems: Comparison of Primary Human Hepatocytes to HepG2 Cells Drug Metab. Dispos., February 1, 2008; 36(2): 223 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Swedenborg, J. Ruegg, A. Hillenweck, S. Rehnmark, M. H. Faulds, D. Zalko, I. Pongratz, and K. Pettersson 3-Methylcholanthrene Displays Dual Effects on Estrogen Receptor (ER) {alpha} and ER{beta} Signaling in a Cell-Type Specific Fashion Mol. Pharmacol., February 1, 2008; 73(2): 575 - 586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Mani, S. Ippolito, J. C. Moreno, T. J. Visser, and K. P. Moore The Metabolism and Dechlorination of Chlorotyrosine in Vivo J. Biol. Chem., October 5, 2007; 282(40): 29114 - 29121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Marroquin, J. Hynes, J. A. Dykens, J. D. Jamieson, and Y. Will Circumventing the Crabtree Effect: Replacing Media Glucose with Galactose Increases Susceptibility of HepG2 Cells to Mitochondrial Toxicants Toxicol. Sci., June 1, 2007; 97(2): 539 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. C.M. Staal, M. H.M. van Herwijnen, F. J. van Schooten, and J. H.M. van Delft Modulation of gene expression and DNA adduct formation in HepG2 cells by polycyclic aromatic hydrocarbons with different carcinogenic potencies Carcinogenesis, March 1, 2006; 27(3): 646 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wen, U.K. Walle, and T. Walle 5,7-Dimethoxyflavone downregulates CYP1A1 expression and benzo[a]pyrene-induced DNA binding in Hep G2 cells Carcinogenesis, April 1, 2005; 26(4): 803 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. M. van Delft, E. van Agen, S. G. J. van Breda, M. H. Herwijnen, Y. C. M. Staal, and J. C. S. Kleinjans Discrimination of genotoxic from non-genotoxic carcinogens by gene expression profiling Carcinogenesis, July 1, 2004; 25(7): 1265 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. V. Nerurkar, K. Dragull, and C.-S. Tang In Vitro Toxicity of Kava Alkaloid, Pipermethystine, in HepG2 Cells Compared to Kavalactones Toxicol. Sci., May 1, 2004; 79(1): 106 - 111. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
