The usefulness of rabbits as an animal model for the neuropathological assessment of neurotoxicity following the administration of vincristine

Vincristine is an effective chemotherapeutic agent for a variety of human n eoplasms, but has dose-limiting neurotoxicity. Since laboratory rodents hav e proven to be refractive in such neurotoxicological studies, we conducted a neuropathological and behavioral assessment in rabbits treated with vincr istine at doses known to be both chemotherapeutically effective and neuroto xic in humans. Rabbits (Kbl: NZW I were given vincristine intravenously at doses of 0 (saline), 200, 250 or 300 mu g/kg once a week for 6 weeks, 500 m u g/kg once a week for 3 weeks, or a single 500 mu g/kg administration. Det ailed periodic neurologic examination revealed ataxia in a few animals. Pat hologically, axonal injury progressing to fiber degeneration was observed i n sensory tracts such as the posterior spinocerebellar tract and posterior funiculus, and in peripheral nerves after treatment with vincristine. These alterations were observed even after a single dose of 500 mu g/kg. In the group given weekly doses of 500 mu g/kg, neuronal chromatolysis was also fo und in the spinal cord. These results suggest the rabbit is responsive to v incristine neurotoxicity producing a predominantly sensory neuropathy and c onfirming earlier studies. (C) 2000 Intox Press, Inc.