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Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights.
- Source :
-
PloS one [PLoS One] 2017 Oct 11; Vol. 12 (10), pp. e0186250. Date of Electronic Publication: 2017 Oct 11 (Print Publication: 2017). - Publication Year :
- 2017
-
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.
- Subjects :
- Acute Disease
Animals
Biopsy
Chronic Disease
Ganglia, Spinal drug effects
Ganglia, Spinal pathology
Gene Expression Regulation drug effects
Mice
Mice, Inbred Strains
Myelin Sheath metabolism
Neural Conduction drug effects
Neuralgia complications
Neuralgia genetics
Neuralgia pathology
Neurons metabolism
Neurons pathology
Neurotoxicity Syndromes complications
Neurotoxicity Syndromes physiopathology
Oxaliplatin
Pain Measurement
Peripheral Nervous System physiopathology
Real-Time Polymerase Chain Reaction
Sciatic Nerve pathology
Sciatic Nerve physiopathology
Skin pathology
Spinal Cord Dorsal Horn drug effects
Spinal Cord Dorsal Horn pathology
Genetic Predisposition to Disease
Neurotoxicity Syndromes genetics
Neurotoxicity Syndromes pathology
Organoplatinum Compounds adverse effects
Peripheral Nervous System pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 29020118
- Full Text :
- https://doi.org/10.1371/journal.pone.0186250