Nerve-growth-factor-dependent neurite outgrowth assay; a research model for chemotherapy-induced neuropathy.
The rat clonal pheochromocytoma cell line PC12 can be induced to display neurite outgrowth upon induction with nerve growth factor (NGF). This NGF-dependent neurite outgrowth assay looks a promising model for research on toxic neuropathies. Using this assay we demonstrated that cisplatin caused a dose-dependent reduction of NGF-dependent neurite formation. Increasing doses of NGF, however, proved to exert protective activity against this cisplatin effect at an intermediate and clinically relevant cisplatin concentration of 1 micrograms/ml. Even at a high cisplatin concentration (10 micrograms/ml), the protective action of NGF, although less adequate, was observed. The value and strength of this model for screening neuropathogenic effects of anticancer agents at the cellular level and the possibly therapeutic action of neurotrophins are discussed and demonstrated. Furthermore, in the light of the urgent need for adequate models for neuropathy research, the PC12 neurite outgrowth protection assay may contribute to our knowledge of the mechanisms underlying the development of neuropathy.
Geldof
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AA
Department Endocrinology/Urology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, The Netherlands.
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D016716:PC12 Cells / Q000187:drug effects; D051381:Rats
D009414:Nerve Growth Factors; D002945:Cisplatin