| Institution: | 1. Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia;2. Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia;3. Radiation Dosimetry and Radiobiology Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia;4. Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10000 Zagreb, Croatia;1. Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, China;2. Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, China;3. Research Institute of Integrated Traditional and Western Medicine of Dalian Medical University, Liaoning, China;1. Institute of Nanostructured Materials, Consiglio Nazionale delle Ricerche, P.le Aldo Moro 5, 00185, Rome, Italy;2. Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, IRCCS- Istituto di Ricerche Farmacologiche “Mario Negri”, V. La Masa 19, Milan, Italy;3. Food and Veterinary Toxicology Unit, Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, V.le Regina Elena 299, 00161, Rome, Italy;4. External Relations Office, Istituto Superiore di Sanità, V. Giano della Bella 34, 00162, Rome, Italy;1. East-Siberian Institute of Medical and Ecological Research, P.O. Box 1170, Angarsk 665827, Russia;2. A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, 33, Leninsky prosp., Moscow 119071, Russia;3. Brooklyn College-CUNY, 2900 Bedford Avenue, Brooklyn, NY 11210-2889, USA |
| 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. |
