title: Integrating transcriptomics and metabonomics to unravel modes-of-action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in HepG2 cells.
abstract: BACKGROUND
  The integration of different 'omics' technologies has already been shown in several in vivo studies to offer a complementary insight into cellular responses to toxic challenges. Being interested in developing in vitro cellular models as alternative to animal-based toxicity assays, we hypothesize that combining transcriptomics and metabonomics data improves the understanding of molecular mechanisms underlying the effects caused by a toxic compound also in vitro in human cells. To test this hypothesis, and with the focus on non-genotoxic carcinogenesis as an endpoint of toxicity, in the present study, the human hepatocarcinoma cell line HepG2 was exposed to the well-known environmental carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
  
  
  RESULTS
  Transcriptomics as well as metabonomics analyses demonstrated changes in TCDD-exposed HepG2 in common metabolic processes, e.g. amino acid metabolism, of which some of the changes only being confirmed if both 'omics' were integrated. In particular, this integrated analysis identified unique pathway maps involved in receptor-mediated mechanisms, such as the G-protein coupled receptor protein (GPCR) signaling pathway maps, in which the significantly up-regulated gene son of sevenless 1 (SOS1) seems to play an important role. SOS1 is an activator of several members of the RAS superfamily, a group of small GTPases known for their role in carcinogenesis.
  
  
  CONCLUSIONS
  The results presented here were not only comparable with other in vitro studies but also with in vivo studies. Moreover, new insights on the molecular responses caused by TCDD exposure were gained by the cross-omics analysis.
authors: Department of Toxicogenomics, Maastricht University, the Netherlands. danyel.jennen@maastrichtuniversity.nl
authors: Danyel
authors: D
authors: Jennen
authors: Ainhoa
authors: A
authors: Ruiz-Aracama
authors: Christina
authors: C
authors: Magkoufopoulou
authors: Ad
authors: A
authors: Peijnenburg
authors: Arjen
authors: A
authors: Lommen
authors: Joost
authors: J
authors: van Delft
authors: Jos
authors: J
authors: Kleinjans
mesh_terms: D002274:Carcinogens, Environmental / Q000633:toxicity*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D049490:Systems Biology / Q000379:methods*
chemical_list: D002274:Carcinogens, Environmental; D000072317:Polychlorinated Dibenzodioxins