Neurotoxicity to DRG neurons varies between rodent strains treated with cisplatin and bortezomib

Jewel L. Podratz, Amit Kulkarni, Josef Pleticha, Rahul Kanwar, Andreas S Beutler, Nathan P Staff, Anthony John Windebank

Research output: Contribution to journalArticle

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Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect that can lead to long-term morbidity. Approximately one-third of patients receiving chemotherapy with taxanes, vinca alkaloids, platinum compounds or proteasome inhibitors develop this toxic side effect. It is not possible to predict who will get CIPN, however, genetic susceptibility may play a role. We explored this hypothesis using an established in vitro dorsal root ganglia neurite outgrowth (DRG-NOG) assay to assess possible genetic influences for cisplatin- and bortezomib-induced neurotoxicity. Almost all previous in vitro studies have used rats or mice. We compared DRG-NOG between four genetically defined, inbred mouse strains (C57BL/6 J, DBA/2 J, BALB/cJ, and C3H/HeJ) and one rat strain (Sprague Dawley). Our studies found differences in cisplatin and bortezomib-induced neurotoxicity between mouse and rat strains and between the different mouse strains. C57BL/6 J and Balb/cJ DRG-NOG was more sensitive to cisplatin than DBA/2 J and C3H/HeJ DRG-NOG, and all mouse strains were more sensitive to cisplatin than rat. Bortezomib induced a biphasic dose response in DBA/2 J and C3H/H3J mice. C57BL/6 J DRG-NOG was most sensitive and Balb/cJ DRG-NOG was least sensitive to bortezomib. Our animal data supports the hypothesis that genetic background may play a role in CIPN and care must be taken when rodent models are used to better understand the contribution of genetics in patient susceptibility to CIPN.

Original languageEnglish (US)
Pages (from-to)131-135
Number of pages5
JournalJournal of the Neurological Sciences
Volume362
DOIs
StatePublished - Mar 15 2016

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Diagnosis-Related Groups
Spinal Ganglia
Cisplatin
Rodentia
Peripheral Nervous System Diseases
Neurons
Drug Therapy
Vinca Alkaloids
Platinum Compounds
Taxoids
Inbred Strains Mice
Proteasome Inhibitors
Inbred C3H Mouse
Poisons
Genetic Predisposition to Disease
Sprague Dawley Rats
Bortezomib
Neuronal Outgrowth
Morbidity

Keywords

  • Bortezomib
  • Cisplatin
  • Genetic variations
  • Mouse strain
  • Neurite outgrowth
  • Neurotoxicity

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Neurotoxicity to DRG neurons varies between rodent strains treated with cisplatin and bortezomib. / Podratz, Jewel L.; Kulkarni, Amit; Pleticha, Josef; Kanwar, Rahul; Beutler, Andreas S; Staff, Nathan P; Windebank, Anthony John.

In: Journal of the Neurological Sciences, Vol. 362, 15.03.2016, p. 131-135.

Research output: Contribution to journalArticle

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