Decoding Short- and Long-Term Cellular Adaptations to Cr(VI) Exposure Through High-Throughput Transcriptomics

Hexavalent chromium (Cr(VI)) is a well-established environmental and occupational carcinogen, but its time-dependent molecular effects remain poorly characterized. This study aims to elucidate the transcriptional responses triggered by acute versus chronic Cr(VI) exposure through an integrated analysis of two publicly available transcriptomic datasets: GSE16349 (short-term exposure, 16 hours) and GSE24025 (long-term exposure, 4 weeks). We identified 250 differentially expressed genes across both exposure models. MetaCore pathway enrichment analysis revealed shared activation of apoptosis, survival signaling, DNA damage response and repair, and cell cycle progression. Notably, short-term exposure primarily activated acute stress responses, whereas long-term exposure induced reprograms transcription toward fibrosis, EMT, and oncogenic signaling. Protein-protein interaction (PPI) network analysis identified potential key hub genes, with potential as biomarkers for Cr(VI) exposure monitoring. Our findings highlight distinct molecular trajectories in response to Cr(VI) over time, providing valuable insights into the progression from early toxic stress to chronic carcinogenic transformation. These results advance our understanding of Cr(VI)-induced carcinogenesis and suggest these potential targets for preventive and therapeutic interventions in exposed populations.