title: The organophosphate insecticide chlorpyrifos confers its genotoxic effects by inducing DNA damage and cell apoptosis.
abstract: The organophosphate insecticide chlorpyrifos (CPF) is known to induce neurological effects, malformation and micronucleus formation, persistent developmental disorders, and maternal toxicity in rats and mice. The binding of chlorpyrifos with DNA to produce DNA adducts leads to an increasing social concern about the genotoxic risk of CPF in human, but CPF-induced cytotoxicity through DNA damage and cell apoptosis is not well understood. Here, we quantified the cytotoxicity and potential genotoxicity of CPF using the alkaline comet assay, γH2AX foci formation, and the DNA laddering assay in order to detect DNA damage and apoptosis in human HeLa and HEK293 cells in vitro. Drosophila S2 cells were used as a positive control. The alkaline comet assay showed that sublethal concentrations of CPF induced significant concentration-dependent increases in single-strand DNA breaks in the treated cells compared with the control. The percentage of γH2AX-positive HeLa cells revealed that CPF also causes DNA double-strand breaks in a time-dependent manner. Moreover, DNA fragmentation analysis demonstrated that exposure to CPF induced a significant concentration- and time-dependent increase in cell apoptosis. We conclude that CPF is a strongly genotoxic agent that induces DNA damage and cell apoptosis.
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Diqiu
authors.initials: D
authors.lastname: Li
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address: qchuang@ecust.edu.cn.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Miaoqing
authors.initials: M
authors.lastname: Lu
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Zhichuan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Mimi
authors.initials: M
authors.lastname: Zong
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address: taolm@ecust.edu.cn.
authors.forename: Liming
authors.initials: L
authors.lastname: Tao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D051379:Mice; D051381:Rats
chemical_list: D007306:Insecticides; D004390:Chlorpyrifos
keywords: Cell apoptosis; Chlorpyrifos; DNA damage; Genotoxicity; H2AX foci