Paraoxon and glyphosate induce DNA double-strand breaks but are not type II topoisomerase poisons

Mutat Res Genet Toxicol Environ Mutagen. 2023 Aug-Sep:890:503657. doi: 10.1016/j.mrgentox.2023.503657. Epub 2023 Jul 6.

Abstract

We tested the hypothesis that the pesticides paraoxon and glyphosate cause DNA double-strand breaks (DSB) by poisoning the enzyme Type II topoisomerase (topo II). Peripheral lymphocytes in G0 phase, treated with the pesticides, plus or minus ICRF-187, an inhibitor of Topo II, were stimulated to proliferate; induced cytogenetic damage was measured. Micronuclei, chromatin buds, nucleoplasmic bridges, and extranuclear fragments were induced by treatments with the pesticides, irrespective of the pre-treatment with ICRF-187. These results indicate that the pesticides do not act as topo II poisons. The induction of DSB may occur by other mechanisms, such as effects on other proteins involved in recombination repair.

Keywords: Clastogenicity; Extranuclear fragments; G0; Micronucleus test.

MeSH terms

  • DNA
  • DNA Topoisomerases, Type II / metabolism
  • Dexrazoxane* / pharmacology
  • Glyphosate
  • Paraoxon
  • Pesticides*
  • Poisons*
  • Topoisomerase II Inhibitors / toxicity

Substances

  • Dexrazoxane
  • Paraoxon
  • Topoisomerase II Inhibitors
  • Poisons
  • DNA Topoisomerases, Type II
  • DNA
  • Pesticides