Up-regulation of apoptosis and regeneration genes in the dorsal root ganglia during cisplatin treatment

Cisplatin is an effective anti-neoplastic drug, but its use is dose-limited due to its association with severe peripheral neurotoxicity. The neurotoxic, effect of cisplatin is believed to result from its accumulation in the dorsal root ganglia (DRG), although the mechanism is not completely understood. We used a rat model of cisplatin neurotoxicity to examine changes in gene expression in the DRG. The results indicate that cisplatin affects the expression of several genes associated with apoptosis (Cdkn1a, Ckap2, Bid3, S100a8, S100a9), inflammation (S100a8, S100a9, Cd163, Mmp9), and nerve growth and regeneration (Mmp9, Gfap,Fabp7). The differential regulation of some of these genes may directly contribute to the neurotoxic effect of cisplatin, while others are likely to be representative of the subsequent cellular response to contain damage and initiate recovery. As such, the identified genes may represent candidate processes and pathways that should be considered as targets for therapeutic intervention in cisplatin-induced neuropathy. (c) 2007 Elsevier Inc. All rights reserved.