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Induction of Apoptosis in Cerebellar Granule Cells by 2,4-Dichlorophenoxyacetic Acid

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Abstract

2,4-Dichlorophenoxyacetic acid (2,4-D) and derivatives are herbicides widely used in Argentina and other parts of the world. Exposure to 2,4-D, its ester and salt formulations, have been associated with a range of adverse health effects in humans and different animal species, from embryotoxicity and teratogenicity to neurotoxicity. In this work, we demonstrate that after 24 hs of treatment with 1 and 2 mM 2,4-D there is an induction of apoptosis in cerebellar granule cells (CGC) in culture. However, with 2 mM 2,4-D one population of CGC developed features of apoptosis while another appeared to die by necrosis. This process is associated with an increase in caspase-3 activity after 12 hs of treatment with the herbicide, which is preceded by cytochrome c release from the mitochondria. Treatment of CGC with 2,4-D appears to induce apoptosis by a direct effect on mitochondria producing cytochrome c release and consequently activation of caspase-3, being mitochondrial damage sufficient for triggering the events that may cause apoptosis.

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Authors and Affiliations

  1. Departamento de Química Biológica, IQUIFIB, Universidad de Buenos Aires, CONICET, Junín 956, Buenos Aires, 1113, Argentina

    K. L. De Moliner, E. Soto & A. M. Adamo

  2. Biochemical and Pharmaceutical Faculty, UNR., Experimental Toxicology Laboratory, Suipacha 531, 2000, Rosario, Argentina

    A. M. Evangelista de Duffard & R. Duffard

Authors
  1. K. L. De Moliner
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  2. A. M. Evangelista de Duffard
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  3. E. Soto
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  4. R. Duffard
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  5. A. M. Adamo
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De Moliner, K.L., Evangelista de Duffard, A.M., Soto, E. et al. Induction of Apoptosis in Cerebellar Granule Cells by 2,4-Dichlorophenoxyacetic Acid. Neurochem Res 27, 1439–1446 (2002). https://doi.org/10.1023/A:1021665720446

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