Linked Life Data

12867492

Source:http://linkedlifedata.com/resource/pubmed/id/12867492

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2003-7-17
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1035-42
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12867492-7-Alkoxycoumarin O-Dealkylase, pubmed-meshheading:12867492-Benzo(a)pyrene, pubmed-meshheading:12867492-Carcinoma, Hepatocellular, pubmed-meshheading:12867492-Cell Line, Tumor, pubmed-meshheading:12867492-Comet Assay, pubmed-meshheading:12867492-Cytochrome P-450 CYP1A1, pubmed-meshheading:12867492-Cytoskeleton, pubmed-meshheading:12867492-Dimethylnitrosamine, pubmed-meshheading:12867492-Dose-Response Relationship, Drug, pubmed-meshheading:12867492-Enzyme Induction, pubmed-meshheading:12867492-Female, pubmed-meshheading:12867492-Gene Expression, pubmed-meshheading:12867492-Hepatocytes, pubmed-meshheading:12867492-Humans, pubmed-meshheading:12867492-Imidazoles, pubmed-meshheading:12867492-Liver Neoplasms, pubmed-meshheading:12867492-Male, pubmed-meshheading:12867492-Metabolic Detoxication, Drug, pubmed-meshheading:12867492-Middle Aged, pubmed-meshheading:12867492-Mutagens, pubmed-meshheading:12867492-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2003
pubmed:articleTitle
Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties.
pubmed:affiliation
German Research Centre for Biotechnology, Organ-und Gewebekultur, Braunschweig, Germany. stefan_wilkening@web.de
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't