In human lung cells, low-dose exposure altered energy use, antioxidant defenses and fat storage within 48 hours.
Researchers exposed human lung epithelial cells to non-cytotoxic concentrations of inorganic arsenic, ranging from 0.5 to 2.0 micromolar, in short- and long-term laboratory models. They combined gene-activity and metabolite measurements to track how the cells responded over time.
Metabolic changes appeared after 48 hours and resembled changes found in cells exposed to 0.5 micromolar arsenic for 24 weeks. The results suggest that arsenic can alter how lung cells produce energy, manage oxidative stress and store fat before the cells undergo transformation associated with cancer development.
Early changes in lung cells
Within 48 hours of low-dose inorganic arsenic exposure, human lung epithelial cells showed increased glutathione synthesis, increased glycolysis—the process cells use to break down sugar for energy—and triglyceride accumulation. These early changes resembled the increased glycolysis and changing fat metabolism seen in the 24-week exposure model.
The researchers describe this as early metabolic rewiring that precedes cell transformation. The concentrations tested were 0.5 to 2.0 micromolar for the short-exposure experiments, with a 0.5-micromolar concentration used in the chronic model.
Why the timing matters
Most people exposed to inorganic arsenic encounter relatively low levels over long periods rather than acutely toxic doses. Identifying metabolic changes that occur early in this process may help researchers understand how exposure could support later cancer-related changes in lung cells.
The metabolic pathways involved could also point to possible targets for preventing or treating lung cancers linked to inorganic arsenic, although this study does not test treatments or establish that these changes cause cancer in people.
Evidence and caveats
The findings come from laboratory experiments in human lung epithelial cells, using integrated measurements of gene activity and cellular metabolites after short- and long-term arsenic exposure. The study supports an association between arsenic exposure and early metabolic changes in these cells.
Cell experiments do not reproduce all the processes involved in human exposure or lung cancer. The abstract does not report results from people or animals, and it does not establish that the observed metabolic changes directly cause later cancer. It also does not test whether targeting these pathways can prevent or treat tumors.
// Source
Archives of Toxicology · 2026 · DOI: 10.1007/s00204-026-04555-0
Authors: Richard N Cassidy, Emily Seburn, Andrew Pyman, Wesley N. Saintilnord, Shania Mittendorf, Youssef A. Hegazy, Ryan D. Sheldon, Darrell P. Chandler, Yvonne N. Fondufe‐Mittendorf
Institutions: Washington University in St. Louis, Van Andel Institute, Loyola University Chicago
