Low-concentration uranium enters the HepG2 cell nucleus rapidly and induces cell stress response

• SIMS is a new elemental imaging technique for uranium distribution in cells.
• Uranium enters cell nuclei very rapidly as a soluble form.
• Uranium quickly induces cell stress responses.
• Cell response leading to cell death is observed when uranium precipitates.
• Low-concentration uranium reinforces the antioxidant system.

This study aimed to compare the cell stress effects of low and high uranium concentrations and relate them to its localization, precipitate formation, and exposure time. The time-course analysis shows that uranium appears in cell nuclei as a soluble form within 5 min of exposure, and quickly induces expression of antioxidant and DNA repair genes. On the other hand, precipitate formations began at the very beginning of exposure at the 300-μM concentration, but took longer to appear at lower concentrations. Adaptive response might occur at low concentrations but are overwhelmed at high concentrations, especially when uranium precipitates are abundant.