Hexahydrocarbon effects on intermediate filament organization in human fibroblasts

We reported previously that 2,5-hexanedione (2,5-HD), the neurotoxic metabolite of methyl-n-butylketone (MnBK) and n-hexane, induced aggregation of intermediate filaments of the vimentin type in cultured fibroblasts. To determine if these findings have relevance to the mechanism by which these hexacarbons induce their filamentous axonopathy, it was necessary to show that only those hexacarbon analogues that induce focal accumulation of neurofilaments in nerve fibers do aggregate intermediate filaments in fibroblasts. We report here that the nonneurotoxic hexacarbons, 1,6-hexanediol and 2,4-hexanedione (2,4-HD), had no primary effect on intermediate filament distribution in fibroblasts, although the profound, nonspecific cytotoxicity of the latter controverted comparisons with equimolar, effective concentrations of 2,5-HD. Fibroblasts did not metabolize MnBK to 2,5-HD sufficiently to induce reproducible aggregation of intermediate filaments in these cells in culture.