2,4-Dichlorophenoxyacetic acid: effects on Syrian hamster embryo (SHE) cell transformation, c-Myc expression, DNA damage and apoptosis

Mutat Res. 2007 Jul 28;631(2):124-36. doi: 10.1016/j.mrgentox.2007.03.008. Epub 2007 Apr 20.

Abstract

2,4-Dichlorophenoxyacetic acid (2,4-D) is a selective, systemic auxin-type herbicide extensively used throughout the world. The present research was aimed at studying effects of low and non-cytotoxic concentrations of 2,4-D on SHE cells in relation with carcinogenicity. Effects were studied on Syrian hamster morphological cell transformation, c-Myc expression - both at the gene and protein level - DNA damage and apoptosis. 2,4-D significantly induced cell transformation at 11.5 microM and 23 microM (i.e. 2.5 microg/mL and 5 microg/mL). An increase in the expression of the transcription factor c-Myc, measured by use of RT-PCR with respect to mRNA level and by Western blotting for protein level was registered at these concentrations, as well as genotoxic effects evaluated with the single-cell gel electrophoresis (Comet) assay. Consequences for apoptosis of 2,4-D treatment were also investigated. The fluorochrome acridine orange was used to study DNA fragmentation as a marker of apoptosis. No effect on apoptosis was found at 2,4-D concentrations that induced cell transformation. This was confirmed by the unchanged expression of Bcl-2 and Bax, two regulator genes of the mitochondrial pathway of apoptosis. Our results demonstrate the transforming and genotoxic effects of low concentrations of 2,4-D in mammalian cells. This information contributes to a better understanding of the mechanism of 2,4-D toxicity in mammalian cells and demonstrates that 2,4-D should be considered as potentially hazardous to humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,4-Dichlorophenoxyacetic Acid / toxicity*
  • Animals
  • Apoptosis / drug effects*
  • Base Sequence
  • Comet Assay
  • Cricetinae
  • DNA Damage*
  • DNA Primers
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / drug effects*
  • Embryo, Mammalian / metabolism
  • Genes, myc*
  • Mesocricetus / embryology
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA Primers
  • 2,4-Dichlorophenoxyacetic Acid