ACRYLAMIDE AND CARBON-DISULFIDE TREATMENTS INCREASE THE RATE OF RAT-BRAIN TUBULIN POLYMERIZATION

Acrylamide and carbon disulfide produce central-peripheral distal axon opathy in experimental animals and humans. The main feature of this di sease is the focal swellings containing neurofilaments in distal axons , followed by nerve degeneration beyond these swellings. We studied th e possible role of tubulin assembly kinetics in this disease. The rats were either administered acrylamide (50 mg/kg, ip, saline) or exposed to carbon disulfide (700 ppm, 9 h) via inhalation for 12 and 15 d, re spectively. Tubulin, purified from both acrylamide- (10.37 +/- 0.3 vs 11.3 +/- 0.15) and carbon disulfide-treated (9.72 +/- 0.5 vs 11.18 +/- 0.25) rat brains showed increase in V-max (OD/min x 10(3)) of its pol ymerization. However, only acrylamide treatment showed a decrease in t ime to V-max, when brain supernatant was used for tubulin polymerizati on. In vitro addition of acrylamide (0.1-1 mM) to bovine brain tubulin also showed a decrease in time to V-max (16-21%) of its polymerizatio n. Carbon disulfide treatment of rats, on the other hand, showed a dec rease in MAP-2 and an increase in a 120-kDa peptide concentration. The latter showed immunoreactivity with anti-MAP-2. The increase in the r ate of tubulin polymerization by acrylamide and carbon disulfide treat ment may alter the rate of transport of axonal constituents, including neurofilament, and contribute toward their accumulation in the focal swellings observed in this neuropathy.