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Neuronal expression of copper transporter 1 in rat dorsal root ganglia: association with platinum neurotoxicity

Citation

Liu, JJ and Jamiesom, SMF and Subramaniam, J and Ip, V and Jong, NN and Mercer, JFB and McKeage, MJ, Neuronal expression of copper transporter 1 in rat dorsal root ganglia: association with platinum neurotoxicity, Cancer Chemotherapy and Pharmacology, 64, (4) pp. 847-856. ISSN 0344-5704 (2009) [Refereed Article]

Copyright Statement

Copyright 2009 Springer-Verlag

DOI: doi:10.1007/s00280-009-1017-6

Abstract

Abstract Purpose We report the neuronal expression of copper transporter 1 (CTR1) in rat dorsal root ganglia (DRG) and its association with the neurotoxicity of platinum-based drugs. Methods CTR1 expression was studied by immunohistochemistry and RT-PCR. The toxicity of platinum drugs to CTR1-positive and CTR1-negative neurons was compared in DRG from animals treated with maximum tolerated doses of oxaliplatin (1.85 mg/kg), cisplatin (1 mg/kg) or carboplatin (8 mg/kg) twice weekly for 8 weeks. Results Abundant CTR1 mRNA was detected in DRG tissue. CTR1 immunoreactivity was associated with plasma membranes and cytoplasmic vesicular structures of a subpopulation (13.6 3.1%) of mainly large-sized (mean cell body area, 1,787 127 lm2) DRG neurons. After treatment with platinum drugs, the cell bodies of these CTR1-positive neurons became atrophied, with oxaliplatin causing the greatest percentage reduction in the mean cell body area relative to controls (42%; P\0.05), followed by cisplatin (18%; P\0.05) and carboplatin causing the least reduction (3.2%; P = NS). CTR1-negative neurons, with no immunoreactivity or only diffuse cytoplasmic staining, showed less treatment-induced cell body atrophy than CTR1-positive neurons. Conclusions CTR1 is preferentially expressed by a subset of DRG neurons that are particularly vulnerable to the toxicity of platinum drugs. These findings, together with its neuronal membrane localization, are suggestive of CTR1- related mechanisms of platinum drug neuronal uptake and neurotoxicity.

Item Details

Item Type:Refereed Article
Keywords:copper transporter 1, platinum neurotoxicity, dorsal root ganglion
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Clinical Pharmacology and Therapeutics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Liu, JJ (Dr Johnson Liu)
ID Code:89121
Year Published:2009
Web of Science® Times Cited:32
Deposited By:Pharmacy
Deposited On:2014-02-25
Last Modified:2014-05-19
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