[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content

Advertisement

Log in

In vitro evaluation of genomic damage induced by glyphosate on human lymphocytes

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Glyphosate is an important broad-spectrum herbicide used in agriculture and residential areas for weed and vegetation control, respectively. In our study, we analyzed the in vitro clastogenic and/or aneugenic effects of glyphosate by chromosomal aberrations and micronuclei assays. Human lymphocytes were exposed to five glyphosate concentrations: 0.500, 0.100, 0.050, 0.025, and 0.0125 μg/mL, where 0.500 μg/mL represents the established acceptable daily intake value, and the other concentrations were tested in order to establish the genotoxicity threshold for this compound. We observed that chromosomal aberration (CA) and micronuclei (MNi) frequencies significantly increased at all tested concentrations, with exception of 0.0125 μg/mL. Vice versa, no effect has been observed on the frequencies of nuclear buds and nucleoplasmic bridges, with the only exception of 0.500 μg/mL of glyphosate that was found to increase in a significant manner the frequency of nucleoplasmic bridges. Finally, the cytokinesis-block proliferation index and the mitotic index were not significantly reduced, indicating that glyphosate does not produce effects on the proliferation/mitotic index at the tested concentrations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Explore related subjects

Discover the latest articles, news and stories from top researchers in related subjects.

Abbreviations

Ab.C:

Aberrant cells

ADI:

Acceptable daily intake

AF:

Acentric fragments

B′:

Chromatid breaks

B″:

Chromosome breaks

BNCs:

Binucleated cells

CAs:

Chromosomal aberrations

CBPI:

Cytokinesis-block proliferation index

DC:

Dicentric

DMSO:

Dimethyl sulfoxide

EFSA:

European Food Safety Authority

IARC:

International Agency for Research on Cancer

JMPR:

Joint FAO/WHO Meeting on Pesticide Residues

MI:

Mitotic index

MMC:

Mitomycin-C

MNC:

Micronucleated cell

MNi:

Micronuclei

MRL:

Maximum residue limits

NBUD:

Nuclear buds

NPB:

Nucleoplasmic bridges

R:

Rings

RfD:

Reference dose

SE:

Standard error

TR:

Tri-tetraradials

US EPA:

US Environmental Protection Agency

References

  • Alvarez-Moya C, Silva MR, Ramírez CV, Gallardo DG, Sanchez RL, Aguirre AC, Velasco AF (2014) Comparison of the in vivo and in vitro genotoxicity of glyphosate isopropylamine salt in three different organisms. Genet Mol Biol 37:105–110

    Article  Google Scholar 

  • Aris A, Leblanc S (2011) Maternal and fetal exposure to pesticides associated to genetically modified foods in eastern townships of Quebec, Canada. Rep Toxicol 31:528–533

    Article  CAS  Google Scholar 

  • Bai SH, Ogbourne SM (2016) Glyphosate: environmental contamination, toxicity and potential risks to human health via food contamination. Environ Sci Pollut Res 23:18988–19001

    Article  CAS  Google Scholar 

  • Bonassi S, Znaor A, Norppa H, Hagmar L (2004) Chromosomal aberrations and risk of cancer in humans: an epidemiologic perspective. Cytogenet Genome Res 104:376–382

    Article  CAS  Google Scholar 

  • Bonassi S, El-Zein R, Bolognesi C (2011) Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies. Mutagenesis 26:93–100

    Article  CAS  Google Scholar 

  • Braz-Mota S, Sadauskas-Henrique H, Duarte RM, Val AL, Almeida-Val VM (2015) Roundup® exposure promotes gills and liver impairments, DNA damage and inhibition of brain cholinergic activity in the Amazon teleost fish Colossoma macropomum. Chemosphere 135:53–60

    Article  CAS  Google Scholar 

  • Duke SO (2017) The history and current status of glyphosate. Pest Manag Sci 74:1027–1034. https://doi.org/10.1002/ps.4652

    Article  CAS  Google Scholar 

  • European Commission (2017) Health and Food Safety Directorate-General. Summary report of the Appeal Committee – Phytopharmaceuticals – Plant protection Products – Legislation. https://ec.europa.eu/food/sites/food/files/plant/docs/sc_phyto_20171127_pppl_summary.pdf. Accessed 02-29-2018

  • European Food Safety Authority (EFSA) (2014) The 2011 European Union report on pesticide residues in food. EFSA J 12:3694 Available from: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2014.3694/epdf. Accessed on 03-09-2018

    Google Scholar 

  • European Food Safety Authority (EFSA) (2015) Conclusion on the peer review of the pesticide risk assessment of the active substance glyphosate (EFSA-Q-2014-00546, EFSA-Q-2015-00279, approved on 30 October 2015 by European Food Safety Authority). EFSA J 13(11):4302 Available from: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2015.4302/epdf. Accessed on 03-09-2018

    Google Scholar 

  • FAO/WHO Joint Meeting on Pesticide Residues (JMPR) (2014) Glyphosate. In: Pesticide residues in food 2013. Joint FAO/WHO meeting on pesticide residues and the WHO core assessment group on pesticide residues, Geneva, 17–26 September 2013. Rome: Food and Agriculture Organization of the United Nations/Geneva, World Health Organization (WHO). (FAO Plant Production and Protection Paper No. 219); pp 225–228. Available from: http://www.fao.org/3/a-i3518e.pdf. Accessed on 03-08-2018

  • FAO/WHO Joint Meeting on Pesticide Residues (JMPR) (2016) Summary report for diazinon, glyphosate, malathion. Geneva, Switzerland: food and agriculture organization of the United Nations/Geneva, World Health Organization (WHO). pp 2. Available from: http://www.who.int/foodsafety/jmprsummary2016.pdf?ua=1. Accesse on 03-08-2018

  • Ferrer E, Santoni E, Vittori S, Font G, Mañes J, Sagratini G (2011) Simultaneous determination of bisphenol a, octylphenol, and nonylphenol by pressurised liquid extraction and liquid chromatography–tandem mass spectrometry in powdered milk and infant formulas. Food Chem 126:360–367

    Article  CAS  Google Scholar 

  • George J, Prasad S, Mahmood Z, Shukla Y (2010) Studies on glyphosate-induced carcinogenicity in mouse skin: a proteomic approach. J Proteome 73:951–964

    Article  CAS  Google Scholar 

  • Hoppe HW, Rüther M, Pieper S, Kolossa-Gehring M (2017) Glyphosate in German adults—time trend (2001 to 2015) of human exposure to a widely used herbicide. Int J Hyg Environ Health 220:8–16

    Article  Google Scholar 

  • International Agency for Research on Cancer (IARC) Working Group (2015) Glyphosate. In: Some Organophosphate Insecticides and Herbicides: Diazinon, Glyphosate, Malathion, Parathion, and Tetrachlorvinphos. IARC Monogr 112:321–399 Available from: http://monographs.iarc.fr/ENG/Monographs/vol112/mono112.pdf. Accessed on 03-08-2018

    Google Scholar 

  • Kašuba V, Milić M, Rozgaj R, Kopjar N, Mladinić M, Žunec S, Vrdoljak AL, Pavičić I, Marjanović Čermak AM, Pizent A, Lovaković BT, Želježić D (2017) Effects of low doses of glyphosate on DNA damage, cell proliferation and oxidative stress in the HepG2 cell line. Environ Sci Pollut Res 24:19267–19281

    Article  Google Scholar 

  • Kier LD, Kirkland DJ (2013) Review of genotoxicity studies of glyphosate and glyphosate-based formulations. Crit Rev Toxicol 43:283–315

    Article  CAS  Google Scholar 

  • King JJ, Wagner RS (2010) Toxic effects of the herbicide roundup® regular on Pacific northwestern amphibians. Northwest Nat 91:318–324

    Article  Google Scholar 

  • Kocaman AY, Rencüzoğullari E, Topaktaş M (2014) In vitro investigation of the genotoxic and cytotoxic effects of thiacloprid in cultured human peripheral blood lymphocytes. Environ Toxicol 29:631–641

    Article  CAS  Google Scholar 

  • Koller V, Fürhacker M, Nersesyan A, Mišík M, Eisenbauer M, Knasmueller S (2012) Cytotoxic and DNA-damaging properties of glyphosate and roundup in human-derived buccal epithelial cells. Arch Toxicol 86:805–813

    Article  CAS  Google Scholar 

  • Kwiatkowska M, Jarosiewicz P, Michałowicz J, Koter-Michalak M, Huras B, Bukowska B (2016) The impact of glyphosate, its metabolites and impurities on viability, ATP level and morphological changes in human peripheral blood mononuclear cells. PLoS One 11:e0156946

    Article  Google Scholar 

  • Kwiatkowska M, Reszka E, Woźniak K, Jabłońska E, Michałowicz J, Bukowska B (2017) DNA damage and methylation induced by glyphosate in human peripheral blood mononuclear cells (in vitro study). Food Chem Toxicol 105:93–98

    Article  CAS  Google Scholar 

  • Lioi MB, Scarfi MR, Santoro A, Barbieri R, Zeni O, Di Berardino D, Ursini MV (1998) Genotoxicity and oxidative stress induced by pesticide exposure in bovine lymphocytes cultures in vitro. Mutat Res 403:13–20

    Article  CAS  Google Scholar 

  • Majewski MS, Coupe RH, Foreman WT, Capel PD (2014) Pesticides in Mississippi air and rain: a comparison between 1995 and 2007. Environ Toxicol Chem 33:1283–1293

    Article  CAS  Google Scholar 

  • Mañas F, Peralta L, Raviolo J, Ovando HG, Weyers A, Ugnia L, Cid MG, Larripa I, Gorla N (2009) Genotoxicity of glyphosate assessed by the comet assay and cytogenetic tests. Environ Toxicol Pharmacol 28:37–41

    Article  Google Scholar 

  • Marc J, Mulner-Lorillon O, Bellé R (2004) Glyphosate-based pesticides affect cell cycle regulation. Biol Cell 96:245–249

    Article  CAS  Google Scholar 

  • Marques A, Guilherme S, Gaivão I, Santos MA, Pacheco M (2014) Progression of DNA damage induced by a glyphosate-based herbicide in fish (Anguilla anguilla) upon exposure and post-exposure periods--insights into the mechanisms of genotoxicity and DNA repair. Comp Biochem Physiol C Toxicol Pharmacol 166:126–133

    Article  CAS  Google Scholar 

  • Mladinic M, Berend S, Vrdoljak AL, Kopjar N, Radic B, Zeljezic D (2009) Evaluation of genome damage and its relation to oxidative stress induced by glyphosate in human lymphocytes in vitro. Environ Mol Mutagen 50:800–807

    Article  CAS  Google Scholar 

  • Piesova E (2005) The effect of glyphosate on the frequency of micronuclei in bovine lymphocytes in vitro. Acta Veter 55:101–109

    Article  Google Scholar 

  • Romano MA, Romano RM, Santos LD, Wisniewski P, Campos DA, de Souza PB, Viau P, Bernardi MM, Nunes MT, de Oliveira CA (2012) Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression. Arch Toxicol 86:663–673

    Article  CAS  Google Scholar 

  • Santovito A, Cannarsa E, Schleicherova D, Cervella P (2018) Clastogenic effects of bisphenol a on human cultured lymphocytes. Hum Exp Toxicol 37:69–77

    Article  CAS  Google Scholar 

  • Šiviková K, Dianovský J (2006) Cytogenetic effect of technical glyphosate on cultivated bovine peripheral lymphocytes. Int J Hyg Environ Health 209:15–20

    Article  Google Scholar 

  • Thongprakaisang S, Thiantanawat A, Rangkadilok N, Suriyom T, Satayavivad J (2013) Glyphosate induces human breast cancer cells growth via estrogen receptors. Food Chem Toxicol 59:129–136

    Article  CAS  Google Scholar 

  • United States Environmental Protection Agency (US EPA) (2012) Glyphosate. Section 3 registration concerning the application of glyphosate to carrots, sweet potato, teff, oilseeds (crop group (CG) 20) and to update the CG definitions for bulb vegetable (CG 3–07), fruiting vegetable (CG 8–10), citrus fruit (CG 10–10), porne fruit (CG 11–10), berry (CG 13–07), human health risk assessment. Washington (DC): U.S. Environmental Protection Agency (US EPA), Office of Chemical Safety and Pollution Prevention (No. Decision No.: 459870); pp 28

  • Yüzbaşioğlu D, Celik M, Yilmaz S, Unal F, Aksoy H (2006) Clastogenicity of the fungicide afugan in cultured human lymphocytes. Mutat Res 604:53–59

    Article  Google Scholar 

  • Zouaoui K, Dulaurent S, Gaulier JM, Moesch C, Lachatre G (2013) Determination of glyphosate and AMPA in blood and urine from humans: about cases of acute intoxication. Forensic Sci Int 226:20–25

    Article  Google Scholar 

Download references

Funding

This research was supported by grant from the Italian Ministry of University and Scientific Research (“ex 60%”).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alfredo Santovito.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Responsible editor: Philippe Garrigues

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Santovito, A., Ruberto, S., Gendusa, C. et al. In vitro evaluation of genomic damage induced by glyphosate on human lymphocytes. Environ Sci Pollut Res 25, 34693–34700 (2018). https://doi.org/10.1007/s11356-018-3417-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-018-3417-9

Keywords

Navigation