Expression of caspase-activated deoxyribonuclease (CAD) and caspase 3 (CPP32) in the cochlea of cisplatin (CDDP)-treated guinea pigs.
Cisplatin, an anti-cancer drug, is known to induce apoptosis. During apoptosis, double-stranded DNA is broken into single-stranded DNA by the action of caspases and caspase activated deoxyribonuclease (CAD). We immunohistochemically examined the cochlea of guinea pigs for signs of the apoptosis after the administration of cisplatin. Cisplatin (10 mg/kg b.w.) was intraperitoneally injected to guinea pigs and 3 days later, the animals were sacrificed by intracardiac perfusion of 4% paraformaldehyde. The temporal bones were then removed and immunohistochemically stained for CAD and caspase 3, using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling method. CAD was observed in the stria vascularis and the spiral ligament. Caspase 3 was also detected in the stria vascularis, the spiral ligament and the supporting cells of the organ of Corti. These findings suggest that apoptosis is involved in the cochlear damage observed in cancer patients treated with cisplatin.
Watanabe
Ken-ichi
K
Department of Oto-Rhino-Laryngology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Kawasaki, Tokyo 113-8603, Japan. bxp02646@nifty.ne.jp
Inai
Shunta
S
Jinnouchi
Ken
K
Baba
Shunkichi
S
Yagi
Toshiaki
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D001309:Auditory Threshold / Q000187:drug effects; D020169:Caspases / Q000032:analysis*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003051:Cochlea / Q000187:drug effects* / Q000201:enzymology*; D003851:Deoxyribonucleases / Q000032:analysis*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006168:Guinea Pigs; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D009925:Organ of Corti / Q000187:drug effects / Q000201:enzymology
D000970:Antineoplastic Agents; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease; D020169:Caspases; D002945:Cisplatin