2,4-Dichlorophenoxyacetic Acid disrupts the cytoskeleton and disorganizes the golgi apparatus of neuron in culture.

ROSSO, S; CÁCERES, A; DUFFARD, R; EVANGELISTA, A; QUIROGA, S

TOXICOLOGICAL SCIENCES

Oxford Univ Press

Lugar: Oxford; Año: 2000 vol. 56 p. 133 - 140

1096-6080

 ",4-D is a potent neurotoxic herbicide widely used in agriculture. The basic mechanism by which 2,4-D produces cell damage have not yet been determined. In this study we have examined the effects of 2,4-D in primary cultures of cerebellar granule cells in order to obtain insights into the possible mechanisms underlying the toxic effects of this herbicide. The results obtained indicate that a 24-h exposure to 2,4-D produces a striking and dose-dependent inhibition of neurite extension. This phenomenon is paralleled by a significant reduction in the cellular content of both dynamic and stable microtubules, a disorganization of the Golgi apparatus, and an inhibition in the synthesis of complex gangliosides. Interestingly, 2,4-D inhibits the in vitro polymerization of purified tubulin. Taken together, the present observations raise the posibility that at least one basic mechanism underlying 2,4-D neurotoxicity involves an inhibition of microtubule assembly. That event may cause a decreased neurite outgrowth response, and could also explain the observed differences in the pattern of ganglioside biosynthesis and/or the disorganization of the Golgi apparatus.