title: Assessment of oxidative stress responses and the cytotoxic and genotoxic potential of the herbicide tembotrione in HepG2 cells.
abstract: Tembotrione is a triketone herbicide, usually used for post-emergence weed control in corn. Currently, there is little or no published data on its genotoxicity to human cells either in vitro or in vivo. This study evaluated the impact of acute (4 and 24 h) exposure to low concentrations of tembotrione [corresponding to the acceptable daily intake (0.17 μg/mL), residential exposure level (0.002 μg/mL) and acceptable operator exposure level (0.0012 μg/mL)] on human hepatocellular carcinoma cell line HepG2, using biomarkers of oxidative stress, CCK-8 colorimetric assay for cell viability, alkaline comet assay, and cytokinesis-block micronucleus "cytome" assay. Tembotrione applied at concentrations likely to be encountered in occupational and residential exposures induced cytogenetic outcomes in non-target cells despite non-significant changes in the values of oxidative stress biomarkers. We assume that the observed effects were mainly the consequence of impaired metabolic pathways in HepG2 cells due to the inhibition of the enzyme 4-hydroxyphenyl-pyruvate-dioxygenase by tembotrione, which possibly caused a depletion of folate levels leading to excess formation of nuclear buds in the affected cells. Regardless of the fact that tembotrione was previously reported negative for mutations and chromosome aberrations in vitro, our findings call for more precaution in its use.
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: 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: 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: 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: 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: 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. Electronic address: nkopjar@imi.hr.
authors.forename: Nevenka
authors.initials: N
authors.lastname: Kopjar
authors.affiliation: Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Alica
authors.initials: A
authors.lastname: Pizent
authors.affiliation: Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Ana Lucić
authors.initials: AL
authors.lastname: Vrdoljak
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: Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia.
authors.forename: Davor
authors.initials: D
authors.lastname: Želježić
mesh_terms: D015197:Carcinogenicity Tests; D003512:Cyclohexanones / Q000633:toxicity*; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D056945:Hep G2 Cells; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D015227:Lipid Peroxidation; D009152:Mutagenicity Tests; D018384:Oxidative Stress / Q000187:drug effects*; D013450:Sulfones / Q000633:toxicity*
chemical_list: D003512:Cyclohexanones; D006540:Herbicides; D013450:Sulfones; D005979:Glutathione Peroxidase; D005978:Glutathione; C585552:tembotrione
keywords: 4-Hydroxyphenyl-pyruvate-dioxygenase; DNA damage; Genome instability; Oxidative stress; Toxicity; Triketone herbicide