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 J. Windebank

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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
StatePublished - Mar 15 2016

Bibliographical note

Funding Information:
This study was funded by NPS: NIH ( K08 CA169443 ), Mayo Clinic Center for Regenerative Medicine and Richard M. Schulze Family Foundation. We thank Jane Meyer for her administrative role in manuscript preparation.

Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.


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


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