DNA repair proteins and telomerase reverse transcriptase in the cochlear lateral wall of cisplatin-treated rats.
Cochlear lateral wall damage is a side effect of cisplatin chemotherapy. Recent studies 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 excision 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 transcriptase (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 proteins and modify teRt expression in the cochlear lateral wall.
Guthrie
O W
OW
Department of Biology, Developmental, Cell and Molecular Biology Group, Duke University, French Family Center, Durham, NC 27708, USA. owg@duke.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000096:biosynthesis / Q000187:drug effects*; D007150:Immunohistochemistry; D051381:Rats; D011916:Rats, Inbred F344; D019098:Telomerase / Q000187:drug effects*; D051760:Xeroderma Pigmentosum Group A Protein / Q000096:biosynthesis / Q000187:drug effects
D000970:Antineoplastic Agents; D002352:Carrier Proteins; C534808:XPC protein, rat; D051760:Xeroderma Pigmentosum Group A Protein; D019098:Telomerase; D045643:DNA Repair Enzymes; D002945:Cisplatin