Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights

Paola Marmiroli, Beatrice Riva, Eleonora Pozzi, Elisa Ballarini, Dmitry Lim, Alessia Chiorazzi, Cristina Meregalli, Carla Distasi, Cynthia L. Renn, Sara Semperboni, Lavinia Morosi, Federico A. Ruffinatti, Massimo Zucchetti, Susan G. Dorsey, Guido Cavaletti, Armando Genazzani, Valentina A. Carozzi

Research output: Contribution to journalArticle

Abstract

Peripheral neurotoxicity is one of the most distressing side effects of oxaliplatin therapy for cancer. Indeed, most patients that received oxaliplatin experience acute and/or chronic severe sensory peripheral neuropathy. However, despite similar co-morbidities, cancer stage, demographics and treatment schedule, patients develop oxaliplatin-induced peripheral neurotoxicity with remarkably different severity. This suggests individual genetic variability, which might be used to glean the mechanistic insights into oxaliplatin neurotoxicity. We characterized the susceptibility of different mice strains to oxaliplatin neurotoxicity investigating the phenotypic features of neuropathy and gene expression profiles in dorsal root ganglia of six genetically different mice strains (Balb-c, C57BL6, DBA/2J, AJ, FVB and CD1) exposed to the same oxaliplatin schedule. Differential gene expression in dorsal root ganglia from each mice strain were assayed using a genome-wide expression analysis and selected genes were validated by RT-PCR analysis. The demonstration of consistent differences in the phenotypic response to oxaliplatin across different strains is interesting to allow the selection of the appropriate strain based on the pre-defined read-out parameters. Further investigation of the correlation between gene expression changes and oxaliplatin-induced neurotoxicity phenotype in each strain will be useful to deeper investigate the molecular mechanisms of oxaliplatin neurotoxicity.

Original languageEnglish
Pages (from-to)e0186250
JournalPLoS One
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights'. Together they form a unique fingerprint.

  • Cite this

    Marmiroli, P., Riva, B., Pozzi, E., Ballarini, E., Lim, D., Chiorazzi, A., Meregalli, C., Distasi, C., Renn, C. L., Semperboni, S., Morosi, L., Ruffinatti, F. A., Zucchetti, M., Dorsey, S. G., Cavaletti, G., Genazzani, A., & Carozzi, V. A. (2017). Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights. PLoS One, 12(10), e0186250. https://doi.org/10.1371/journal.pone.0186250