title: Cell line-specific oxidative stress in cellular toxicity: A toxicogenomics-based comparison between liver and colon cell models.
abstract: Imbalance between high reactive oxygen species formation and antioxidant capacity in the colon and liver has been linked to increased cancer risk. However, knowledge about possible cell line-specific oxidative stress-mechanisms is limited. To explore this further, gene expression data from a human liver and colon cell line (HepG2/Caco-2), both exposed to menadione and H2O2 at six time points (0.5-1-2-4-8 and 24h) were compared in association with cell cycle distribution. In total, 3164 unique- and 1827 common genes were identified between HepG2 and Caco-2 cells. Despite the higher number of unique genes, most oxidative stress-related genes such as CAT, OGG1, NRF2, NF-κB, GCLC, HMOX1 and GSR were differentially expressed in both cell lines. However, cell-specific regulation of genes such as KEAP1 and GCLM, or of the EMT pathway, which are of pathophysiological importance, indicates that oxidative stress induces different transcriptional effects and outcomes in the two selected cell lines. In addition, expression levels and/or -direction of common genes were often different in HepG2 and Caco-2 cells, and this led to very diverse downstream effects as confirmed by correlating pathways to cell cycle changes. Altogether, this work contributes to obtaining a better molecular understanding of cell line-specific toxicity upon exposure to oxidative stress-inducing compounds.
authors: Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands. Electronic address: l.deferme@maastrichtuniversity.nl.
authors: L
authors: L
authors: Deferme
authors: Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands.
authors: J J
authors: JJ
authors: Briedé
authors: Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands.
authors: S M H
authors: SM
authors: Claessen
authors: Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands.
authors: R
authors: R
authors: Cavill
authors: Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands.
authors: J C S
authors: JC
authors: Kleinjans
mesh_terms: D018938:Caco-2 Cells; D002453:Cell Cycle / Q000235:genetics; D003106:Colon / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008099:Liver / Q000166:cytology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D043922:Toxicogenetics; D024483:Vitamin K 3 / Q000633:toxicity
chemical_list: D024483:Vitamin K 3; D006861:Hydrogen Peroxide
keywords: Colon; Liver; Oxidative stress; Pathway analysis; Toxicity; Transcriptomics