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Pregled bibliografske jedinice broj: 841218

Genotoxicity assessment of low dose exposure to glyphosate in HepG2 cell line after 4 and 24 hours

Kašuba, Vilena; Milić, Mirta; Rozgaj, Ružica; Kopjar, Nevenka; Mladinić, Marin; Želježić, Davor
Genotoxicity assessment of low dose exposure to glyphosate in HepG2 cell line after 4 and 24 hours // Abstract Book ICOETOX 2016 / Teixeira, João Paulo (ur.).
Porto, Portugal, 2016. str. 33-33 (poster, međunarodna recenzija, sažetak, znanstveni)

Genotoxicity assessment of low dose exposure to glyphosate in HepG2 cell line after 4 and 24 hours

Kašuba, Vilena ; Milić, Mirta ; Rozgaj, Ružica ; Kopjar, Nevenka ; Mladinić, Marin ; Želježić, Davor

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Abstract Book ICOETOX 2016 / Teixeira, João Paulo - Porto, Portugal, 2016, 33-33

International Conference of Environmental and Occupational Health and Ibero-American Meeting on Toxicology and Environmental Health 2016

Mjesto i datum
Porto, Portugal, 21.-23.06.2016

Vrsta sudjelovanja

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Glyphosate; comet assay; NOAEL

The huge expansion of genetically modified plants designed to tolerate high levels of glyphosate has made it the world’s most widely used herbicide. Nevertheless, there are controversies about its use ; the WHO and IARC have been unable to reach an agreement with the EFSA regarding its further use and distribution ever since the former proclaimed glyphosate a probably carcinogenic to humans in March 2015. The aim of this study was to evaluate the genotoxic effects of the glyphosate active compound (Sigma Aldrich) on human liver cell line HepG2 after 4 and 24 hour in vitro exposures to low concentrations chosen as representative of everyday exposure to glyphosate and calculated by approximations and extrapolations based on the no observed adverse effect level (NOEL). The calculation to in vitro conditions was based on an average male human with 65 kg of body weight and a total volume of extracellular liquids, simulating the submersion of cultured cells in culture medium with these exact glyphosate concentrations: acceptable daily intake (ADI:0.3mg/kg corresponds to 0.5μg/ml in HepG2 cell line treatment), residential exposure level (REL:1.75 mg/kg corresponds to 2.91 μg/ml) and occupational exposure limit (OEL:2.1 mg/kg corresponds to 3.5 μg/ml). The HepG2 cell model system (EMEM medium with 10% foetal bovine serum and antibiotics) covers a wide spectrum of enzymes represented in metabolism phases I and II and represents cells of the liver, a major detoxification organ. The alkaline comet assay was chosen for genotoxicity assessment with its two parameters: tail length (TL) and tail intensity (TI). Experiments were done in duplicate with 100 nucleoids counted for each concentration and time period. Positive controls were 50μM H202 and 28μg/ml cyclophosphamide. After 4h, the TL of the control had higher values (only EMEM medium, 17.20±4.29 (mean±SD)) with significant differences from ADI (14.97±1.91) and REL (14.23±1.23). For TI values, all of the concentrations were significantly lower than the control (1.45±2.43): ADI (0.16±0.27), OEL (0.16±0.26) and REL (0.20±0.33). After 24h, values for ADI, OEL and REL did not significantly differ from the control for both TL (13.91±1.76 ; 15.35±1.95 ; 13.97±2.08 vs. 14.91±2.41) and TI (0.06±0.10 ; 0.05±0.09 ; 0.11±0.16 vs. 0.06±0.10). Since commercial compounds usually produce greater DNA damage than observed in this study, which is due to the mixture of different compounds that also produce damage, the use of only the active compound form of pesticide could have been a limiting factor in the DNA damage assessment. The results following 4h exposure indicate a possibility of DNA crosslinking that diminishes the amount of the observed DNA damage. Further studies should be performed with commercial glyphosate products as well as in order to examine whether there is a real crosslinking effect.

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Projekt / tema
HRZZ-IP-2013-11-8366 - Organska zagađivala u okolišu - markeri i biomarkeri toksičnosti (Davor Želježić, )