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Cytotoxic and DNA-damaging properties of glyphosate and Roundup in human-derived buccal epithelial cells

Abstract

Glyphosate (G) is the largest selling herbicide worldwide; the most common formulations (Roundup, R) contain polyoxyethyleneamine as main surfactant. Recent findings indicate that G exposure may cause DNA damage and cancer in humans. Aim of this investigation was to study the cytotoxic and genotoxic properties of G and R (UltraMax) in a buccal epithelial cell line (TR146), as workers are exposed via inhalation to the herbicide. R induced acute cytotoxic effects at concentrations >40 mg/l after 20 min, which were due to membrane damage and impairment of mitochondrial functions. With G, increased release of extracellular lactate dehydrogenase indicative for membrane damage was observed at doses >80 mg/l. Both G and R induced DNA migration in single-cell gel electrophoresis assays at doses >20 mg/l. Furthermore, an increase of nuclear aberrations that reflect DNA damage was observed. The frequencies of micronuclei and nuclear buds were elevated after 20-min exposure to 10–20 mg/l, while nucleoplasmatic bridges were only enhanced by R at the highest dose (20 mg/l). R was under all conditions more active than its active principle (G). Comparisons with results of earlier studies with lymphocytes and cells from internal organs indicate that epithelial cells are more susceptible to the cytotoxic and DNA-damaging properties of the herbicide and its formulation. Since we found genotoxic effects after short exposure to concentrations that correspond to a 450-fold dilution of spraying used in agriculture, our findings indicate that inhalation may cause DNA damage in exposed individuals.

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Abbreviations

BN-MNi:

Binucleated cells with micronuclei

G:

Glyphosate

LDHe:

Extracellular lactate dehydrogenase

MNi:

Micronuclei

NB:

Nuclear buds

NDI:

Nuclear division index

NPB:

Nucleoplasmic bridge

NR:

Neutral red

R:

Roundup-Ultramax

SRB:

Sulforhodamine B

XTT:

2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenyl-amino)carbonyl]-2H-tetrazolium hydroxide

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Correspondence to Siegfried Knasmueller.

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Koller, V.J., Fürhacker, M., Nersesyan, A. et al. Cytotoxic and DNA-damaging properties of glyphosate and Roundup in human-derived buccal epithelial cells. Arch Toxicol 86, 805–813 (2012). https://doi.org/10.1007/s00204-012-0804-8

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Keywords

  • Glyphosate
  • Roundup
  • Cytotoxic
  • Comet assay
  • Micronuclei
  • Buccal cells