title: Cytotoxic, genotoxic and biochemical markers of insecticide toxicity evaluated in human peripheral blood lymphocytes and an HepG2 cell line.
abstract: This study evaluated the cyto- and genotoxic effects of three pesticides: α-cypermethrin, chlorpyrifos and imidacloprid applied in vitro to human lymphocytes and HepG2 cells for exposure times of 4 and 24 h at concentrations corresponding to OEL, ADI and REL. Assessments were made using oxidative stress biomarkers and the alkaline comet, cytokinesis-block micronucleus cytome and cell viability assays. Low doses of all three pesticides displayed DNA damaging potential, both in lymphocytes and HepG2 cells. At the tested concentrations, all three compounds induced lymphocyte apoptosis, though α-cypermethrin and chlorpyrifos were generally more cyto- and genotoxic than imidacloprid. At the tested concentrations, oxidative stress biomarkers were not significantly altered, and the effects mediated indirectly through free radicals may not have a key role in the formation of DNA damage. It is likely that the DNA damaging effects were caused by direct interactions between the tested compounds and/or their metabolites that destabilized the DNA structure. The tested pesticides had the potential for MN, NB and NPB formation and to disturb cell cycle kinetics in both cell types. There were also indications that exposure to α-cypermethrin led to the formation of crosslinks in DNA, though this would require more detailed study in the future.
authors.affiliation: Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Davor
authors.initials: D
authors.lastname: Želježić
authors.affiliation: Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Marin
authors.initials: M
authors.lastname: Mladinić
authors.affiliation: Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Suzana
authors.initials: S
authors.lastname: Žunec
authors.affiliation: Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Lucić Vrdoljak
authors.affiliation: Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Vilena
authors.initials: V
authors.lastname: Kašuba
authors.affiliation: Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Blanka
authors.initials: B
authors.lastname: Tariba
authors.affiliation: Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Živković
authors.affiliation: Radiation Dosimetry and Radiobiology Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Ana Marija
authors.initials: AM
authors.lastname: Marjanović
authors.affiliation: Radiation Dosimetry and Radiobiology Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pavičić
authors.affiliation: Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Mirta
authors.initials: M
authors.lastname: Milić
authors.affiliation: Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Ružica
authors.initials: R
authors.lastname: Rozgaj
authors.affiliation: Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia. Electronic address: nkopjar@imi.hr.
authors.forename: Nevenka
authors.initials: N
authors.lastname: Kopjar
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects*; D004390:Chlorpyrifos / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007093:Imidazoles / Q000633:toxicity; D015151:Immunoblotting; D007306:Insecticides / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D015162:Micronucleus Tests; D000073943:Neonicotinoids; D009574:Nitro Compounds / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D011722:Pyrethrins / Q000633:toxicity
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; D011722:Pyrethrins; C017160:cypermethrin; C082359:imidacloprid; D004390:Chlorpyrifos
keywords: Alkaline comet assay; Cell viability; Chlorpyrifos; Cytokinesis-block micronucleus cytome assay; Imidacloprid; α-cypermethrin