DNA Repair Proteins and Telomerase Reverse Transcriptase in the Cochlear Lateral Wall of Cisplatin-Treated Rats

Abstract

Cochlear lateral wall damage is a side effect of cisplatin chemotherapy. Recent stud-ies have shown that cisplatin treatment precipitates platinated DNA adducts in the cochlear lateral wall which suggest that DNA damage may contribute to ototoxicity. platinated adducts are high-affinity substrates for the global genomic nucleotide exci-sion repair (GG-NER) pathway which is facilitated by xeroderma pigmentosum (XP) complementing proteins, such as XPC, XPD and XPA. Tumor biology has shown that in addition to stimulating GG-NER, cisplatin may deplete telomerase reverse tran-scriptase (TERT). In the current study Fischer344 rats were treated with cisplatin (2 mg/kg/4 days, i.p.) and their cochleae harvested for immunohistochemistry. XPC, XPD and XPA expression increased while TERT expression decreased among cisplatin treated animals compared to vehicle control. These findings suggest that in addition to forming platinated adducts, cisplatin chemotherapy may up-regulate DNA repair pro-teins and modify TERT expression in the cochlear lateral wall.

Keywords:

• Cisplatin
• cochlear lateral wall
• nucleotide excision repair
• telomerase reverse transcriptase
• xeroderma pigmentosum