Roundup® confers cytotoxicity through DNA damage and Mitochondria-Associated apoptosis induction

Environ Pollut. 2019 Sep;252(Pt A):917-923. doi: 10.1016/j.envpol.2019.05.128. Epub 2019 May 29.

Abstract

Glyphosate-based herbicides (GBH) are the most widely used pesticides in the world. The extensive use of them increases the potential human health risk, including the human inhalation toxicity risk. We studied the effect of the most famous GBH Roundup® (RDP) in the concentration range from 50 to 125 μg/mL on Mitochondria-Associated apoptosis and DNA damage in Human alveolar carcinoma cells (A549 cells). Alkaline comet assay, immunofluorescence assay and Flow Cytometric Analysis assay were employed to detect DNA damages and apoptosis of A549 cells. We found RDP caused concentration-dependent increases in DNA damages and proportion of apoptotic cells in A549 cells. RDP induced the DNA single-strand breaks and double-strand breaks; the collapse of mitochondrial membrane by increasing Bax/Bcl-2, resulting in the release of cytochrome c into cytosol and then activated caspase-9/-3, cleaved poly (ADP-ribose) polymerase (PARP) in human lung tissue cells. The results demonstrate that RDP can induce A549 cells cytotoxic effects in vitro at the concentration lower than the occupational exposures level of workers, which means RDP has a potential threat to human health.

Keywords: Cytotoxicity; DNA damage; Glyphosate-based herbicide; Human health risk; Mitochondria-associated apoptosis.

MeSH terms

  • A549 Cells
  • Adenocarcinoma, Bronchiolo-Alveolar / genetics
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Comet Assay
  • Cytochromes c / metabolism
  • DNA Breaks, Double-Stranded / drug effects
  • DNA Breaks, Single-Stranded / drug effects
  • Glycine / analogs & derivatives*
  • Glycine / toxicity
  • Glyphosate
  • Herbicides / toxicity*
  • Humans
  • Lung / pathology*
  • Mitochondria / drug effects*
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • BCL2 protein, human
  • Herbicides
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Cytochromes c
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • Caspase 9
  • Glycine