An ultrastructural study of methyl ethyl ketone's effect on cultured nerve tissues

Clinical and experimental animal studies have firmly established that concomitant exposure to methyl ethyl ketone (MEK) and n-hexane accelerates the onset and severity of hexacarbon neuropathy. This phenomenon was demonstrated recently in an organotypic tissue culture system, consisting of mouse nerve and muscle co-cultures (Veronesi et al., 1984). This study also reported that cultures exposed to noncytotoxic doses of MEK alone and in combination with n-hexane developed intra-axonal inclusions containing axoplasmic debris. The present study was undertaken to detail further the morphological effects of MEK on cultured nerve tissue. Explants of mouse spinal cord with attached dorsal root ganglia were treated with MEK (300 micrograms/ml) for periods of 7 weeks and sampled intermittently for electron microscopy. Early and persistent morphological changes seen in the cytoplasm of both motor and sensory neurons included dispersed Nissl bodies and swollen granular endoplasmic reticulum. Both central and peripheral axons contained excessive agranular reticulum, swollen with a translucent material. In later stages, foci of axoplasmic debris developed, encircled by membranous profiles. These changes suggest that in culture, MEK affects neuronal metabolism and displays neurotoxic properties after prolonged exposure.