2,4-Dichlorophenoxyacetic acid disrupts the cytoskeleton and disorganizes the Golgi apparatus of cultured neurons.
2,4-Dichlorophenoxyacetic acid (2,4-D) is a potent neurotoxic herbicide widely used in agriculture. The basic mechanisms 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-hour 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 possibility 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.
Rosso
S B
SB
Laboratorio de Toxicología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.
Cáceres
A O
AO
de Duffard
A M
AM
Duffard
R O
RO
Quiroga
S
S
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect; D005690:Galactose / Q000378:metabolism; D005732:Gangliosides / Q000096:biosynthesis; D006056:Golgi Apparatus / Q000187:drug effects* / Q000473:pathology; D006540:Herbicides / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D014404:Tubulin / Q000378:metabolism
D005732:Gangliosides; D006540:Herbicides; D014404:Tubulin; D015084:2,4-Dichlorophenoxyacetic Acid; D004247:DNA; D005690:Galactose