ACTION OF VINCA ALKALOIDS VINCRISTINE, VINBLASTINE, AND DESACETYL VINBLASTINE AMIDE ON AXONAL FIBRILLAR ORGANELLES INVITRO

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  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (5) , 1401-1407
Abstract
Axonal ultrastructural changes induced by 3 [antitumor] Vinca alkaloids, vincristine, vinblastine and desacetyl vinblastine amide, were studied in vitro at concentrations of 0.01, 0.05 and 0.1 mM in the cat vagus nerve. Disruption of microtubules, appearance of paracrystalline structures and increase in neurofilaments were induced by all 3 agents at 0.1 mM. A new type of paracrystal with an electron dense central core in each subunit was also observed with each drug. Whereas all 3 compounds affected unmyelinated fibers (vinblastine more so than the other 2), only vinblastine significantly damaged the myelinated fibers. The greater effectiveness of vinblastine in causing these in vitro ultrastructural changes contrasts strikingly with the clinical in vivo situation in which vincristine is the most neurotoxic. This suggests that clinical neurotoxicity is associated with additional factors aside from the direct interaction of the Vinca alkaloids with microtubules or tubulin.