Assessment of oxidative stress responses and the cytotoxic and genotoxic potential of the herbicide tembotrione in HepG2 cells

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 tembotrio...

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Published in:Food and chemical toxicology 2016-08, Vol.94, p.64-74
Main Authors: Žunec, Suzana, Kašuba, Vilena, Pavičić, Ivan, Marjanović, Ana Marija, Tariba, Blanka, Milić, Mirta, Kopjar, Nevenka, Pizent, Alica, Vrdoljak, Ana Lucić, Rozgaj, Ružica, Želježić, Davor
Format: Article
Language:English
Subjects:
4-Hydroxyphenyl-pyruvate-dioxygenase
Carcinogenicity Tests
Cyclohexanones - toxicity
DNA Damage
Genome instability
Glutathione - metabolism
Glutathione Peroxidase - metabolism
Hep G2 Cells
Herbicides - toxicity
Humans
Lipid Peroxidation
Mutagenicity Tests
Oxidative stress
Oxidative Stress - drug effects
Sulfones - toxicity
Toxicity
Triketone herbicide
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Summary: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. [Display omitted] •The in vitro toxicity profile of tembotrione was studied in HepG2 cells.•Most of the oxidative stress markers were not significantly changed.•HepG2 viability remained in the physiological range.•Tembotrione did not cause significant primary DNA damage.•Increased nuclear budding is a matter of concern, and suggests genome instability.
ISSN:0278-6915
1873-6351
DOI:10.1016/j.fct.2016.05.019