In vitro and in vivo studies of the molecular pathogenesis of n-Hexane neuropathy.

In vivo intoxication of rats with 2,5-hexanedione and 3,4-dimethyl-2,5-hexanedione, which results in axonal swellings filled with neurofilaments, has been combined with in vitro exposure of proteins and model amines to the gamma-diketones in attempts to explain the molecular pathogenesis of n-hexane neuropathy and related neurofilament neuropathies. The heretofore untested gamma-diketone, 3,4-dimethyl-2,5-hexanedione is proposed as a "missing link" between beta, beta'-iminodipropionitrile, which produces proximal aggregates of neurofilaments, and 2,5-hexanedione, acrylamide, and carbon disulfide, which result in neurofilament-filled swellings in the distal axon.