Distinct Interactions of Arsenite and Cadmium with Metal Homeostasis and the Cellular Stress Response in Human Bronchial Epithelial Cells

Although exposure to heavy metals such as cadmium and inorganic arsenic has declined in recent decades, they remain prevalent environmental contaminants in food, drinking water, and tobacco smoke. This study aimed to identify and compare molecular endpoints of arsenite and cadmium toxicity at the gene and protein expression levels, with a focus on metal homeostasis, the oxidative stress response and redox-regulated processes. Human bronchial epithelial cells (BEAS-2B) were used as an in vitro model. First, the appropriate exposure conditions were defined by assessing cytotoxicity and intracellular metal accumulation. The cells were then incubated with 1–10 µM NaAsO$_2$ or 1–5 µM CdCl$_2$ for 24 h, after which gene and protein expression were analyzed. When compared to arsenite, cadmium was a markedly stronger inducer of metallothionein (MT) expression, indicating distinct effects on metal homeostasis. Both metals induced a concentration-dependent upregulation of oxidative stress-related genes. Cadmium led to a stronger activation of NF-κB signaling, while arsenite decreased selenoprotein-associated gene expression and affected genes involved ferroptosis regulation. ... mehrDifferences in gene and protein expression patterns were also observed, suggesting that transcriptional responses do not necessarily translate into corresponding changes at the protein level after 24 h. These findings highlight shared and compound-specific mechanisms, as well as the importance of multi-level analyses.