In vivo -- in vitro toxicogenomic comparison of TCDD-elicited gene expression in Hepa1c1c7 mouse hepatoma cells and C57BL/6 hepatic tissue

Dere, Edward; Boverhof, Darrell R; Burgoon, Lyle D; Zacharewski, Timothy R
January 2006
BMC Genomics;2006, Vol. 7, p80
Academic Journal
Background: In vitro systems have inherent limitations in their ability to model whole organism gene responses, which must be identified and appropriately considered when developing predictive biomarkers of in vivo toxicity. Systematic comparison of in vitro and in vivo temporal gene expression profiles were conducted to assess the ability of Hepa1c1c7 mouse hepatoma cells to model hepatic responses in C57BL/6 mice following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Results: Gene expression analysis and functional gene annotation indicate that Hepa1c1c7 cells appropriately modeled the induction of xenobiotic metabolism genes in vivo. However, responses associated with cell cycle progression and proliferation were unique to Hepa1c1c7 cells, consistent with the cell cycle arrest effects of TCDD on rapidly dividing cells. In contrast, lipid metabolism and immune responses, representative of whole organism effects in vivo, were not replicated in Hepa1c1c7 cells. Conclusion: These results identified inherent differences in TCDD-mediated gene expression responses between these models and highlighted the limitations of in vitro systems in modeling whole organism responses, and additionally identified potential predictive biomarkers of toxicity.


Related Articles

  • Practical Application of Toxicogenomics for Profiling Toxicant-Induced Biological Perturbations. Kiyosawa, Naoki; Manabe, Sunao; Yamoto, Takashi; Sanbuissho, Atsushi // International Journal of Molecular Sciences;Sep2010, Vol. 11 Issue 9, p3397 

    A systems-level understanding of molecular perturbations is crucial for evaluating chemical-induced toxicity risks appropriately, and for this purpose comprehensive gene expression analysis or toxicogenomics investigation is highly advantageous. The recent accumulation of toxicity-associated...

  • A Comparison of Gene Expression Responses in Rat Whole Embryo Culture and In Vivo: Time-Dependent Retinoic Acid-Induced Teratogenic Response. Robinson, Joshua F.; Verhoef, Aart; Pennings, Jeroen L. A.; Pronk, Tessa E.; Piersma, Aldert H. // Toxicological Sciences;Mar2012, Vol. 126 Issue 1, p242 

    The whole embryo culture (WEC) model serves as a potential alternative for classical in vivo developmental toxicity testing. In the WEC, cultured rat embryos are exposed during neurulation and early organogenesis and evaluated for morphological effects. Toxicogenomic-based approaches may improve...

  • Relationship between Hepatic Gene Expression Profiles and Hepatotoxicity in Five Typical Hepatotoxicant-Administered Rats. Minami, Keiichi; Saito, Toshiro; Narahara, Masatoshi; Tomita, Hiroyuki; Kato, Hirokazu; Sugiyama, Hisashi; Katoh, Miki; Nakajima, Miki; Yokoi, Tsuyoshi // Toxicological Sciences;Sep2005, Vol. 87 Issue 1, p296 

    In the field of gene expression analysis, DNA microarray technology has a major impact on many different areas including toxicogenomics, such as in predicting the adverse effects of new drug candidates and improving the process of risk assessment and safety evaluation. In this study, we...

  • Temporal Concordance Between Apical and Transcriptional Points of Departure for Chemical Risk Assessment. Thomas, Russell S.; Wesselkamper, Scott C.; Wang, Nina Ching Y.; Zhao, Q. Jay; Petersen, Dan D.; Lambert, Jason C.; Cote, Ila; Yang, Longlong; Healy, Eric; Black, Michael B.; Clewell, Harvey J.; Allen, Bruce C.; Andersen, Melvin E. // Toxicological Sciences;Jul2013, Vol. 134 Issue 1, p180 

    Editor’s Highlight: In this manuscript, a temporal comparison between in vivo gene expression and histologic markers of toxicity demonstrates significant concordance. These results shed light on which gene changes may be the most important for targeted in vivo analysis and additional...

  • OPTIMIZATION OF AN ANIMAL TEST PROTOCOL FOR TOXICOGENOMICS STUDIES (II); A CROSS-LABORATORY GENE EXPRESSION ANALYSIS. Sumida, Kayo; Saito, Koichi; Oeda, Kenji; Otsuka, Masanori; Tsujimura, Kazunari; Miyaura, Hideki; Sekijima, Masaru; Nakayama, Koji; Kawano, Yukiko; Kawakami, Yuki; Asamoto, Makoto; Shirai, Tomoyuki // Journal of Toxicological Sciences;Feb2007, Vol. 32 Issue 1, p33 

    Toxicogenomics is a promising new tool for prediction of chemical toxicities including carcinogenicity in a relatively short period. However, it is important to develop a reliable animal test protocol for toxicogenomics studies. The preparation of RNA and tissues is also crucial, since it...

  • Transferases and transporters mediate the detoxification and capacity to tolerate trinitrotoluene in Arabidopsis. Landa, Premysl; Storchova, Helena; Hodek, Jan; Vankova, Radomira; Podlipna, Radka; Marsik, Petr; Ovesna, Jaroslava; Vanek, Tomas // Functional & Integrative Genomics;Nov2010, Vol. 10 Issue 4, p547 

    The effect of recalcitrant soil and water pollutant 2,4,6-trinitrotoluen (TNT) on gene expression in Arabidopsis thaliana rosettes and roots was studied separately for the first time using microarrays. Seven-day exposure to TNT resulted in 170 up- and 122 down-regulated genes in the rosettes and...

  • SAFETY BIOMARKERS: Toxicology's Holy Grail. Mitchell, Pete; Branca, Malorye A. // Pharma DD: Tracking Discovery & Development;Jul/Aug2006, Vol. 1 Issue 1, p22 

    The article focuses on the challenge of finding safety biomarkers for clinical trials in human beings. It cites new predictors such as animal serum troponins which is a promising alternative biomarker for cardiotoxicity and gene expression changes for certain proteins that appear highly...

  • Analysis of cell death inducing compounds. Spicker, Jeppe S.; Pedersen, Henrik Toft; Nielsen, Henrik Bjørn; Brunak, Søren // Archives of Toxicology;Nov2007, Vol. 81 Issue 11, p803 

    Biomarkers for early detection of toxicity hold the promise of improving the failure rates in drug development. In the present study, gene expression levels were measured using full-genome RAE230 version 2 Affymetrix GeneChips on rat liver tissue 48 h after administration of six different...

  • Performance of Novel Kidney Biomarkers in Preclinical Toxicity Studies. Hoffmann, Dana; Adler, Melanie; Vaidya, Vishal S.; Rached, Eva; Mulrane, Laoighse; Gallagher, William M.; Callanan, John J.; Gautier, Jean C.; Matheis, Katja; Staedtler, Frank; Dieterle, Frank; Brandenburg, Arnd; Sposny, Alexandra; Hewitt, Philip; Ellinger-Ziegelbauer, Heidrun; Bonventre, Joseph V.; Dekant, Wolfgang; Mally, Angela // Toxicological Sciences;Jul2010, Vol. 116 Issue 1, p8 

    The kidney is one of the main targets of drug toxicity, but early detection of renal damage is often difficult. As part of the InnoMed PredTox project, a collaborative effort aimed at assessing the value of combining omics technologies with conventional toxicology methods for improved...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics