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J Chemother ; 21(1): 74-9, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19297277

RESUMEN

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.


Asunto(s)
Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Cóclea/efectos de los fármacos , Cóclea/metabolismo , Enzimas Reparadoras del ADN/efectos de los fármacos , Telomerasa/efectos de los fármacos , Animales , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/efectos de los fármacos , Enzimas Reparadoras del ADN/biosíntesis , Inmunohistoquímica , Ratas , Ratas Endogámicas F344 , Proteína de la Xerodermia Pigmentosa del Grupo A/biosíntesis , Proteína de la Xerodermia Pigmentosa del Grupo A/efectos de los fármacos
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