Transcriptomic Analysis Reveals the Synergistic Mechanisms of Arsenic-Induced DNA Damage and Cell Apoptosis in Pancreatic β-cells

Arsenic is a widely existing environmental pollutant that induces Pancreatic β-cells and promotes the development of type 2 diabetes mellitus (T2DM). However, the molecular mechanism by which arsenic exposure leads to Pancreatic β-cell death has not been fully elucidated. In this study, pancreatic β-cell line, INS-1 cells, were treated with sodium arsenite (NaAsO ₂ ) to assess cell death and DNA damage, combined with transcriptome sequencing to investigate the underlying molecular mechanisms. The data indicated that arsenic treatment decreased INS-1 cell viability, increased apoptosis rates, disrupted the balance of apoptosis-related proteins, and elevated the DNA damage marker 8-hydroxy-2’-deoxyguanosine (8-OHdG). Transcriptome analysis identified 8,341 differentially expressed genes, including 5,072 up-regulated and 3,269 down-regulated genes. Enrichment analysis showed that up-regulated genes were mainly enriched in cytochrome P450 (CYP450) metabolism and chemical carcinogen-DNA adduct pathways, while down-regulated genes were primarily enriched in DNA repair pathways. The findings from the Western blot analysis demonstrated that there was an up-regulation of protein levels for Cyp2e1 and Gsta2, both of which are integral components of the CYP450 metabolic pathway. In conclusion, our findings indicate that arsenic exposure concurrently impairs cellular detoxification functions and hinders DNA repair mechanisms, thereby synergistically inducing apoptosis in pancreatic β-cells.