Evidence for cross linking of neurofilament (NF) proteins in rat spinal cord following inhalation exposure to carbon disulfide.
Wilmarth-KR; Viana-ME; Abou-Donia-MB
Toxicologist 1994 Mar; 14(1):205
Chronic exposure to CS2 produces morphological changes in the distal regions of long myelinated fibers characterized by perinodal accumulation of neurofilaments in axonal swellings. CS2 has also been reported to bind neuronal proteins in vivo and covalently crosslink bovine serum albumin in vitro. In this study, male Sprague-Dawley rats were exposed to 50, 100, or 200 ppm CS2 via inhalation 12h/day for 140 consecutive days. 24h following the end of treatment, animals were sacrificed and cytoskeletal proteins were isolated from spinal cords of individual animals. Proteins were resolved by SDSPAGE and stained with Coomassie Blue, or transferred to nitrocellulose and probed with monoclonal antisera against NF200, 160 and 68kD. We observed a significant decrease in the intensity of protein staining and immunoreactivity of all three NF protein bands as well as decreased immunoreactive breakdown products in animals exposed to 200 ppm CS2. A dose dependent increase in the appearance of multiple bands migrating between 260 and 400 kD with immunoreactivity against NF 160 and NF68 antibodies was also observed. The relative increase in immunoreactivity against the proteins with increasing levels of exposure was NFI6Q>NF68. These results suggest that CS2 induced cross linking of NF proteins may be involved in the aggregation of NFcharacteristic of this neuropathy.
Laboratory-testing; Toxins; Toxicology; Toxic-effects; Exposure-assessment; Exposure-levels; Laboratory-animals; Animal-studies; Central-nervous-system; Chronic-exposure; Chronic-toxicity
The Toxicologist. Society of Toxicology 33rd Annual Meeting, March 13-17, 1994, Dallas, Texas
Duke University Medical Center, Durham, North Carolina