Exposure to glyphosate and tetrachlorvinphos induces cytotoxicity and global DNA methylation in human cells


Ergun H., ÇAYIR A.

TOXICOLOGY AND INDUSTRIAL HEALTH, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2021
  • Doi Number: 10.1177/07482337211033149
  • Title of Journal : TOXICOLOGY AND INDUSTRIAL HEALTH
  • Keywords: DNA methylation, organophosphate pesticide, glyphosate, tetrachlorvinphos, gene expression, PESTICIDE EXPOSURE, EPIGENETICS, MECHANISMS, EXPRESSION, CLONING

Abstract

Two organophosphate pesticides-glyphosate and tetrachlorvinphos-have been announced as carcinogens to humans by various authorities, including the European Chemical Agency and the Environmental Protection Agency. We aimed to investigate molecular mechanisms associated with carcinogenicity and to examine changes in global m(5)C DNA methylation and cytotoxic potential in A549 lung epithelial cells in response to glyphosate and tetrachlorvinphos, and differential gene expression of m(5)C DNA methyltransferase genes in Sprague Dawley rats to Roundup (commercial formulation of glyphosate). Global m(5)C level significantly increased after 1500 mu M glyphosate exposure for 24 h. We determined that exposure to tetrachlorvinphos did not significantly increase the m(5)C level in A549 cells for 24 h. Additionally, we did not observe significant DNA methylation alteration for both pesticides after 12 h exposure. In the animal study, we observed that DNA methyltransferase genes (DNMT3b and DNMT3a) showed significantly higher expression in Roundup-exposed rats than the control group in the liver and kidney. We also observed that a significant cytotoxic effect was determined after the treatment of the cells with higher concentrations of glyphosate and tetrachlorvinphos. Our results revealed that DNA methylation could be modified by exposure to glyphosate and that exposure to Roundup was associated with the differential expression level of m(5)C DNA methylation methyltransferase. Finally, exposure to both pesticides increased cytotoxicity.