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| Status |
Public on Jan 01, 2009 |
| Title |
Acetaminophen-induced gene expression profiles in sandwich-cultured primary human hepatocytes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct comparison of toxicant-induced gene expression profiles and infers mechanisms between several systems. In the present study, acetaminophen (APAP) was used as a model compound to compare gene expression responses between rat and human using in vitro cellular models, hepatocytes, and between rat in vitro and in vivo. Comparison at the level of modulated biochemical pathways and biological processes rather than at that of individual genes appears preferable as it increases the overlap between various systems. Pathway analysis by T-profiler revealed similar biochemical pathways and biological processes repressed in rat and human hepatocytes in vitro, as well as in rat liver in vitro and in vivo. Repressed pathways comprised energy-consuming biochemical pathways, mitochondrial function, and oxidoreductase activity. Conclusion: the present study is the first that used a toxicogenomics-based parallelogram approach, extrapolating in vitro to in vivo and interspecies, to reveal relevant mechanisms indicative of APAP-induced liver toxicity in humans in vivo.
expression profiles of sandwich-cultured primary human hepatocytes exposed to 5 mM and 10 mM acetaminophen were used in a parallelogram approach in order to compare gene expression responses between rat and human using in vitro cellular models, hepatocytes, and between rat in vitro and in vivo.
Keywords: Toxicogenomics, dose response
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| Overall design |
Samples were retrieved from acetaminophen treated human hepatocyte cultures from 5 individuals (5 biological replicates).
Human hepatocytes from each replicate were treated with 0, 5, and 10 mM acetaminophen for 24 h.
This resulted in (3x5) 15 dual channel arrays on which control (0 mM acetaminophen) and reference samples (0, 5, and 10 mM acetaminophen) were hybridized.
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| Contributor(s) |
Kienhuis A, van de Poll MC, van Herwijnen M, Gottschalk R, Dejong CH, Kleinjans JC, Stierum RH, van Delft JH |
| Citation(s) |
19008212 |
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| Submission date |
Nov 01, 2008 |
| Last update date |
Dec 06, 2012 |
| Contact name |
Anne Susan Kienhuis |
| E-mail(s) |
[email protected]
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| Organization name |
RIVM
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| Street address |
A. van Leeuwenhoeklaan 9
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| City |
Bilthoven |
| ZIP/Postal code |
3720 BA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL887 |
Agilent-012097 Human 1A Microarray (V2) G4110B (Feature Number version) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA110013 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE13430_RAW.tar |
61.1 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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