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.