2,4-Dichlorophenoxyacetic acid: effects on Syrian hamster embryo (SHE) cell transformation, c-Myc expression, DNA damage and apoptosis.
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.
Maire
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Laboratoire Ecotoxicité Santé Environnementale, CNRS UMR 7146, Université de Metz, UFR Sciences Fondamentales et Appliquées, Rue Général Delestraint, 57070 Metz, France.
Rast
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C
Landkocz
Y
Y
Vasseur
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P
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D020552:Comet Assay; D006224:Cricetinae; D004249:DNA Damage; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016259:Genes, myc; D008647:Mesocricetus / Q000196:embryology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D015084:2,4-Dichlorophenoxyacetic Acid