title: The insecticide spinosad induces DNA damage and apoptosis in HEK293 and HepG2 cells.
abstract: 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.
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Guanggang
authors.initials: G
authors.lastname: Xiang
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Diqiu
authors.initials: D
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Xu
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: taolm@ecust.edu.cn.
authors.forename: Liming
authors.initials: L
authors.lastname: Tao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay / Q000379:methods; D004249:DNA Damage / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004338:Drug Combinations; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007306:Insecticides / Q000009:adverse effects*; D018942:Macrolides / Q000009:adverse effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D007306:Insecticides; D018942:Macrolides; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; C415329:spinosad
keywords: Apoptosis; Comet assay; Cytotoxic; DNA damage; H2AX foci; Spinosad