Cell line-specific oxidative stress in cellular toxicity: A toxicogenomics-based comparison between liver and colon cell models

- HepG2 and Caco-2 cells showed a substantial overlap in oxidative stress related genes.
- However, expression levels/direction of common DEGs were often different in these cells.
- And oxidative stress induces different transcriptional effects and outcomes in these cell.
- These changes led to diverse downstream effects as confirmed by correlating pathways.

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 24 h) 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.