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

Regina Montero-Montoya1, Karen Suárez-Larios1, Luis Serrano-García1

  • 1Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, 04510 Ciudad de México, Mexico.

Mutation Research. Genetic Toxicology and Environmental Mutagenesis
|August 11, 2023
PubMed

Insights

This study found that pesticides paraoxon and glyphosate do not poison the enzyme Type II topoisomerase (Topo II). DNA double-strand breaks (DSB) are induced by these pesticides through alternative mechanisms.

Area of Science:

  • Environmental toxicology
  • Molecular toxicology
  • Genetics

Background:

  • Pesticides like paraoxon and glyphosate are widely used, raising concerns about their genotoxicity.
  • Type II topoisomerase (Topo II) is a critical enzyme for DNA replication and repair, and its inhibition can lead to DNA damage.

Purpose of the Study:

  • To investigate whether paraoxon and glyphosate induce DNA double-strand breaks (DSB) by inhibiting the enzyme Type II topoisomerase (Topo II).

Main Methods:

  • Peripheral lymphocytes were treated with paraoxon and glyphosate, with or without ICRF-187 (a Topo II inhibitor).
  • Cells were stimulated to proliferate, and cytogenetic damage, including micronuclei and other aberrations, was measured.

Main Results:

  • Paraoxon and glyphosate induced significant cytogenetic damage (DSB).
  • This damage occurred independently of pre-treatment with ICRF-187, indicating that the pesticides do not act as Topo II poisons.
  • The findings suggest alternative mechanisms for pesticide-induced DNA damage.

Conclusions:

  • Paraoxon and glyphosate do not function as Topo II poisons.
  • The induction of DNA double-strand breaks by these pesticides likely involves other cellular pathways, potentially affecting proteins in recombination repair.
Keywords:
ClastogenicityExtranuclear fragmentsG0Micronucleus test

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