Nucleolar damage correlates with neurotoxicity induced by different platinum drugs

摘要: Platinum-based drugs are very useful in cancer therapy but associated with neurotoxicity the clinic. To investigate mechanism of neurotoxicity, dorsal root ganglia rats treated various platinum were studied. Cell body, nuclear and nucleolar dimensions sensory nerve cells measured to determine morphological toxicity. Sensory conduction velocity was functional After a single dose oxaliplatin (10 mg kg–1), no significant change cell body diameter seen decreased size apparent within few hours treatment. Changes maximal at 24 hours, recovered slowly showed non-linear dependence on (r2= 0.99). Functional toxicity delayed onset until 14 days after eventually 3 months Multiple doses cisplatin, carboplatin, oxaliplatin, R, R -ormaplatin S, S also time-dependent reduction size. A linear correlation obtained between rate during multiple treatment series time taken for development altered 0.86;P< 0.024). Damage nucleolus ganglionic neurons is therefore linked platinum-based drugs, possibly through mechanisms resulting inhibition rRNA synthesis. © 2001 Cancer Research Campaign http://www.bjcancer.com