The insecticide spinosad induces DNA damage and apoptosis in HEK293 and HepG2 cells

- This study evaluates the cytotoxicity of spinosad and its mode of action in HEK293 and HepG2 cells.
- Spinosad induced increases on single- and double-strand DNA breaks in HEK293 and HepG2 cells.
- DNA damage-induced p53 accumulation and modulation of Bcl-2/Bax ratio in HEK293 and HepG2 cells.
- Spinosad induced disruption of the mitochondrial membrane potential in HEK293 and HepG2 cells.
- Spinosad induced apoptosis in HEK293 and HepG2 cells through mitochondrial pathways.

Spinosad, a pesticide acting on the central nervous system of insects, is classified as a pesticide with reduced risk. However, spinosad-induced toxicological effects on non-target organisms must not be ignored. This study aimed to evaluate the cytotoxicity and potential genotoxicity of spinosad in HEK293 and HepG2 cell lines. The results showed that spinosad caused a concentration- and time-dependent decrease in cell viability of HEK293 and HepG2 cells. Spinosad-induced p53 accumulation thereby upregulates the expression of Bax and downregulates the expression of Bcl-2. Further studies confirmed that spinosad induced apoptosis in HEK293 and HepG2 cells, accompanied by a dissipation of the mitochondrial membrane potential and an increase in caspase-3 activity. The alkaline comet assay and γ-H2AX foci staining revealed that spinosad induced significant concentration-dependent increases of DNA strand breaks in HEK293 and HepG2 cells. Our results indicate that spinosad effectively induced DNA damage and apoptosis in HEK293 and HepG2 cells.