Comparison of the neurotoxic effects of colchicine, the vinca alkaloids, and other microtubule poisons.
Previous studies have revealed that colchicine is selectively toxic to certain neuronal populations in the CNS, particularly granule cells of the dentate gyrus. The present study evaluates whether other microtubule poisons exhibit similar neurotoxic effects. Equimolar solutions of colchicine, colcemid, podophyllotoxin, vinblastine, vincristine and lumicolchine, the non-binding analog of colchicine, were injected into the dentate gyrus. Neurotoxicity was evaluated histologically. As previously reported, colchicine selectively destroyed dentate granule cells with minimal damage to other neurons including hippocampal pyramidal cells. Vincristine was very toxic and was not selective for granule cells. Vinblastine was relatively selective in destroying granule cells, but was not as potent as colchine. Colcemid and podophyllotoxin had minimal toxic effects. Lumicolchine injections caused no more damage than injections of vehicle. This ordering appears to correlate with the reversibility of binding tubulin.
Goldschmidt
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RB
Department of Neuroscience, University of Virginia School of Medicine, Charlottesville 22908.
Steward
O
O
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D003078:Colchicine / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008297:Male; D008870:Microtubules / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014748:Vinca Alkaloids / Q000633:toxicity*
D014748:Vinca Alkaloids; D003078:Colchicine