The anthracycline compound doxorubicin, used in the treatment of malignant tumors, produced a sensory neuronopathy in experimental animals. Rats which had received a single intravenous dose of 10 mg/kg developed a progressive hind-limb ataxia without apparent weakness 11 or 12 days after treatment. Examination revealed neuronal degeneration in the ganglia of the peripheral nervous system. Nuclear changes appearing as early as 3 hours post-injection wer followed by cytoplasmic degeneration visible by 9 days. At least one half of the normal population of neurons was lost by day 34. Secondary degeneration of sensory nerve fibers in peripheral nerves and dorsal columns of spinal cord was apparent. These neuronal changes may be explained by 1) the known selective permeability of blood vessels in the peripheral ganglia, 2) intercalation of doxorubicin nucleic acids and 3) resultant permanent disruption of nucleic acid metabolism in neurons.
|Original language||English (US)|
|Number of pages||9|
|State||Published - Jan 1 1980|
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