Immunohistochemical detection of platinated DNA in the cochlea of cisplatin-treated guinea pigs.
Cisplatin-induced ototoxicity is correlated with functional and morphological changes in the organ of Corti, the stria vascularis and the spiral ganglion. However, the cochlear sites of cisplatin uptake and accumulation have not been properly identified. Therefore, we have developed an immunohistochemical method to, indirectly, detect cisplatin in semithin cryosections of the guinea pig cochlea (basal turn) using an antiserum containing antibodies against cisplatin-DNA adducts. Platinated DNA was present in the nuclei of most cells in the organ of Corti and the lateral wall after cisplatin administration. Nuclear immunostaining was most pronounced in the outer hair cells, the marginal cells and the spiral ligament fibrocytes. This study is the first to demonstrate the presence of cisplatin in histological sections of the cochlea.
van Ruijven
Marjolein W M
MW
Hearing Research Laboratories, Department of Otorhinolaryngology, University Medical Center Utrecht, Room G.02.531, P.O. Box 85.500, 3508 GA Utrecht, The Netherlands. m.vanruijven@kmb.azu.nl
de Groot
John C M J
JC
Hendriksen
Ferry
F
Smoorenburg
Guido F
GF
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007672:Kidney Cortex / Q000166:cytology / Q000378:metabolism; D009925:Organ of Corti / Q000166:cytology / Q000378:metabolism; D013194:Staining and Labeling; D014018:Tissue Distribution
D018736:DNA Adducts; C057270:cisplatin-DNA adduct; D002945:Cisplatin