The neurotoxins 2,5-hexanedione and acrylamide promote aggregation of intermediate filaments in cultured fibroblasts.

Axonal swellings associated with large aggregates of neurofilaments are characteristic of neuropathies caused by chemical neurotoxins (n-hexane, methyl n-butyl ketone, and acrylamide) or giant axonal neuropathy (GAN--an autosomal recessive genetic disease). In GAN, filamentous aggregates have been shown also to occur in other cell types including cultured skin fibroblasts. Therefore, we studied the effects of 2,5-hexanedione (the neurotoxic metabolite of n-hexane and methyl n-butyl ketone) and acrylamide on normal human skin fibroblasts in tissue culture. We show that both neurotoxins induce aggregation of intermediate filaments of the vimentin type in the cultured fibroblasts without disrupting microtubules.