The Effect of Some Dithiocarbamates, Disulfiram and 2,5-Hexanedione on the Cytoskeleton of Neuronal Cells inVivo and inVitro

  • Veli-Pekka Lehto
  • Ismo Virtanen
  • Kai Savolainen


Dithiocarbamates are widely used fungicides because of their low toxicity to mammalian species and because of their rather rapid biodégradation in the soil and by plants. Their fungicidal action is based on interference with the citric acid cycle of several fungi (Schlagbauer and Schlagbauer, 1972). Several dithiocarbamates show neurotoxic effects in central and peripheral nervous system (Seppalainen and Linnoila, 1976; Freudenthal et al., 1977; Chernoff et al., 1979), but the mechanisms of the neurotoxicity of dithiocarbamates are largely unexplained.


Sciatic Nerve Intermediate Filament Carbon Disulfide Original Magnification Carbonyl Sulfide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allen, N., Mendell, J.R., Billmaier, D.J., Fontaine, R.E., and O’Neill, J., 1975, Toxic polyneuropathy produced by industrial solvent methyl-n-butyl ketone, Arch. Neurol., 32: 209–218.Google Scholar
  2. Altmannsberger, M., Osborn, M., Schauer, A., and Weber, K., 1981, Antibodies to different intermediate filament proteins. Cell type-specific markers on paraffin-embedded human tissues, Lab. Invest., 45: 427–434.Google Scholar
  3. Ausbacher, L.E., Bosch, E.P., and Cancilla, P.A., 1982, Disulfiram neuropathy: a neurofilamentous distal axonopathy, Neurology, 32: 424–428.Google Scholar
  4. Anzil, A.P., 1980, Selected aspects of experimental disulfiram neuromyopathy, in: “Advances in Neurotoxicology,” L. Manzo, I. Laxasse and L. Roche, eels., pp. 359–366, Pergamon Press, New York.Google Scholar
  5. Augusti-Tocco, G., and Sato, G., 1969, Establishment of functional clonal lines of neurons from mouse neuroblastoma, Proc. Natl. Acad. Sci., 64: 311–315.CrossRefGoogle Scholar
  6. Autio, K., 1982, Ethylenethiourea: metabolism, analysis and aspects of toxicity, Dissertation, Technical Research Centre of Finland, Research Report 91, Espoo.Google Scholar
  7. Bouldin, T.W., Hall, C.D., and Krigman, M.R., 1980, Pathology of disulfiram neuropathy, Neuropath. Appl. Neurobiol., 6: 155–160.CrossRefGoogle Scholar
  8. Chengelis, C.P., and Neal, R.A., 1980, Studies of carbonyl sulfide toxicity: metabolism by carbonic anhydrase, Toxicol. Appl.Pharmacol., 55: 198–204.CrossRefGoogle Scholar
  9. Chernoff, N., Karlock, R.I., Rogers, E.H., Carver, B.D., and Murray, S., 1979, Perinatal toxicity of maneb, ethylene thiourea and ethylenebisisothiocyanate sulfide in rodents, J. Toxicol. Environ. Health, 5: 821–834.CrossRefGoogle Scholar
  10. Dalvi, R.R., Hunter, A., and Neal, R.A., 1975, Toxicological implications of the mixed function oxidase catalyzed metabolism of carbon disulfide, Chem.-Biol. Interact., 10: 347–361.Google Scholar
  11. Di Vincenzo, G., Kaplan, C.J., and Dedinas, J., 1976, Characterization of the metabolites of methyl-n-butyl ketone, metyl isobutyl ketone and metyl ethyl ketone in guinea-pig serum and their clearance, Toxicol. Appl.Pharmacol., 36: 511–522.CrossRefGoogle Scholar
  12. Durham, H.D., Pena, S.D.J., and Carpenter, S., 1983, The neurotoxins 2,5-hexanedione and acrylamide promote aggregation of intermediate filaments in cultured fibroblasts, Muscle and Nerve, 6: 631–637.CrossRefGoogle Scholar
  13. Faiman, M.D., Artman, L., and Haya, K., 1980, Disulfiram distribution and elimination in the rat after oral and intraperitoneal administration, Alcoholism: Clin. Exp. Res., 4: 412–419.CrossRefGoogle Scholar
  14. Flshbein, L., 1976, Environmental health aspects of fungicides, I. Dithiocarbamates, J. Toxicol. Environm. Health., 1: 713–735.CrossRefGoogle Scholar
  15. Freudenthal, R.I., Kerchner, G.A., Persing, R.L., Baumell, I., and Baron, R.L., 1977, Subacute toxicity of ethylenbisisothiocyanate sulfide in the laboratory rat, J. Toxicol. Environ. Health, 2: 1067–1078.Google Scholar
  16. Graham, D.G., 1980, Hexane neuropathy: a proposal for pathogenesis of a hazard of occupational exposure and inhalant abuse, Chem.-Biol. Interactions, 32: 339–345.CrossRefGoogle Scholar
  17. Graham, S.L., and Hansen, W.H., 1972, Effects of short-term administration of ethylenethiourea upon thyroid function of the rat, Bull. Environ. Contam. Toxicol. ( U.S. ), 7: 19–25.CrossRefGoogle Scholar
  18. Griffin, J.W., Price, D.L., and Hoffman, P.N., 1983, Neurotoxic probes of the axonal cytoskeleton, Trends in Neurol.Sci., 6: 490–495.CrossRefGoogle Scholar
  19. Heikkila, R.E., Cabbat, F.S., and Cohen, G., 1976, In vivo inhibition of superoxide dismutase in mice by diethyldithiocarbamate, J. Biol. Chem., 251: 2182–2185.Google Scholar
  20. Herskowitz, A., Ishii, N., and Schaumburg, H.H., 1971, n-Hexane neuropathy: A syndrome occurring as a result of industrial exposure, N. Engl. J. Med., 285: 82–85.Google Scholar
  21. Hodge H.C., Maynard, E.A., Downs, W., Blanchet, H.J., and Jones, C.K., 1952, Acute and short-term oral toxicity tests of ferbam and ziram, Am. Pharm. Assoc., 41: 662–666.CrossRefGoogle Scholar
  22. Hodgson, J.R., Hoch, J.C., Castles, T.R., Helton, D.O., and Lee, C.-C., 1975, Metabolism and disposition of febram in the rat, Toxicol. Appl. Pharmacol., 33: 505–513.CrossRefGoogle Scholar
  23. Kappus, H., and Sies, H., 1981, Toxic drug effects associated with oxygen metabolism: Redox cycling and lipid peroxidation, Experientia, 37: 1233–1241.Google Scholar
  24. Lee, C.-C., Russell, J.Q., and Minor, J.L., 1978, Oral toxicity of ferric dimethyldithiocarbamate (ferbam) and tetramethylthiourea disulfide (thiram) in rodents, J. Toxicol. Environm. Health, 4: 93–106.CrossRefGoogle Scholar
  25. Lehto, V.-P., and Virtanen, I., 1983, Immunolocalization of a novel, cytoskeleton-associated polypeptide of Mr 230,000 daltons (p230), J. Cell Biol., 96: 703–716.CrossRefGoogle Scholar
  26. Lehtonen, E., Lehto, V.-P., and Virtanen, I., 1983, Parietal and visceral endoderm differ in their expression of intermediate filaments, EMBO J., 2: 1023–1028.Google Scholar
  27. Moddel, G., Bilbao, J.M., Payne, D., and Ashby, P., 1978, Disulfiram neuropathy, Arch. Neurol., 35: 658–660.Google Scholar
  28. Mokri, B., Ohnishi, A., and Dyck, P.J., 1981, Disulfiram neuropathy, Neurology, 31: 730–735.Google Scholar
  29. Pannese, E., Procacci, P., Ledda, M., Arcidiacono, G., and Rigamonti, L., 1984, A quantitative study of microtubules in motor and sensory axons, Acta. Anat., 118: 193–200.CrossRefGoogle Scholar
  30. Prasad, K.N., 1975, Differentiation of neuroblastoma cells in culture, Biol. Rev., 50: 129–165.Google Scholar
  31. Prasad, K.N., and Hsie, A.W., 1971, Morphologic differentiation of mouse neuroblastoma cells induced in vitro by dibutyryl adenosine 3′5′-cyclomonophosphate, Nature New Biol., 233: 141–142.Google Scholar
  32. Rainey, J.M., 1977, Disulfiram toxicity and carbon disulfide poisoning, Am. J. Psychiatry, 134: 371–378.Google Scholar
  33. Sauter, M., and von Wartburg, J.P., 1977, Quantitative analysis of disulfiram and its metabolites in human blood by gas-liquid chromatography, J. Chromatogr., 133: 167–172.CrossRefGoogle Scholar
  34. Savolainen, K., Hervonen, H., Lehto, V.-P., and Mattila, M.J., 1983, Neurotoxic effects of disulfiram on autonomic and peripheral nervous system in rat, Toxicol. Lett. Suppl., 1: 34.CrossRefGoogle Scholar
  35. Savolalnen, H., Lehtonen, E. and Vainio, H., 1977, CS2 binding to rat spinal neurofilaments, Acta Neuropathol., 37: 219–224.CrossRefGoogle Scholar
  36. Savolainen, H., Tenhunen, R., Elovaara, E., and Tossavainen, A., 1980, Cumulative biochemical effects of repeated subclinical hydrogen sulfide intoxication in mouse brain, Int. Arch. Environ. Health., 46: 87–92.Google Scholar
  37. Schlagbauer, B.G.L., and Schlagbauer, A.W.J., 1972, The metabolism of carbamate pesticides, Residue Rev., 42: 1–84.Google Scholar
  38. Seppalainen, A.M., and Linnoila, I., 1976, Electrophysiological findings in rats with experimental carbon disulfide neuropathy, Neuropath. Appl. Neurobiol, 2: 209–215.CrossRefGoogle Scholar
  39. Seppalainen, A. M., and Haltia, M., 1980, Carbon disulfide, in: “Experimental and Clinical Neurotoxicology,” P.S. Spencer and H.H. Sc Faumburg, eds., pp. 356–373, Williams and Wilkins, Baltimore.Google Scholar
  40. Spencer, P.S., Schaumburg, H.H., Sabri, M.I., and Veronesi, B., 1980, The enlarging view of hexacarbon neurotoxicity, CRC Crit. Rev. Toxicol., 7: 279–350.CrossRefGoogle Scholar
  41. Sterman, A.B., and Schaumburg, H.H., 1980, Neurotoxicity of selected drugs, in: “Experimental and Clinical Neurotoxicity,” P.S. Spencer and H.H. Schaumburg, eds., pp. 593–612, Williams and Wilkins, Baltimore.Google Scholar
  42. Virtanen, I., Lehto, V.-P., Lehtonen, E., Vartio, T., Stenman, S., Kurki, P., Wager, O., Small, J.Y., Dahl, D., and Badley, R.A., 1981, Expression of intermediate filaments in cultured cells, J. Cell Sci., 50: 45–63.Google Scholar
  43. Virtanen, I., Miettinen, M., Lehto, V.-P., Kariniemi, A.-L., and Paasivuo, R., 1984, Diagnostic application of monoclonal antibodies to intermediate filaments, Ann. N.Y. Acad. Sci., in press.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Veli-Pekka Lehto
    • 1
  • Ismo Virtanen
    • 1
  • Kai Savolainen
    • 2
  1. 1.Department of PathologyUniversity of HelsinkiHelsinkiFinland
  2. 2.Department of Environmental Hygiene and ToxicologyNational Public Health InstituteKuopioFinland

Personalised recommendations