title: Comparative analysis of perturbed molecular pathways identified in in vitro and in vivo toxicology studies.
abstract: The development of in vitro toxicological testing strategies are hampered by the difficulty in extrapolation to the intact organism. Academic toxicological literature contains a wealth of mechanistically rich information, especially arising from omic studies, which could potentially be utilized to uncover commonalities between in vitro and in vivo observations on the cellular level. Using a literature mining strategy, we identified 1221 unique human genes as being associated to nephrotoxicity, hepatotoxicity, or CNS toxicity, either linked to in vitro, in vivo, or both experimental conditions. Among this large set of relevant molecular features four genes were found in common to all tissues and experimental conditions analyzed, namely heme oxygenase-1, nitric oxide synthetase 2, NFκB1 and p53. Pathway enrichment revealed 17 relevant pathways for kidney, 26 for liver, and 30 for CNS bridging in vitro and in vivo toxicity effects. Such joint markers and pathways may serve as indicators for extrapolating from in vitro results to in vivo.
authors.affiliation: emergentec biodevelopment GmbH, Gersthofer Strasse 29-31, 1180 Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Wiesinger
authors.forename: Bernd
authors.initials: B
authors.lastname: Mayer
authors.forename: Paul
authors.initials: P
authors.lastname: Jennings
authors.forename: Arno
authors.initials: A
authors.lastname: Lukas
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002493:Central Nervous System Diseases / Q000235:genetics*; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D008107:Liver Diseases / Q000235:genetics*; D018675:Toxicity Tests
chemical_list: D015415:Biomarkers