Apoptosis

, 11:2127 | Cite as

Dose-dependant radiation-induced apoptosis in a cochlear cell-line

  • Wong-Kein Low
  • Michelle G. K. Tan
  • Li Sun
  • Alvin W. C. Chua
  • Lip-Kai Goh
  • De-Yun Wang
Article

Abstract

Cisplatin and gentamycin are both ototoxic and they have been shown to induce cochlear cell apoptosis. Although radiation is also ototoxic, radiation-induced apoptosis in cochlear cells has not been studied. This study aimed to investigate the biophysical changes of dose-related radiation-induced cochlear cell apoptosis in an experimental model. Post gamma-irradiation apoptosis was demonstrated in the cochlear cell-line OC-k3 by flow cytometry and TUNEL assay. This was dose-dependant with enhanced apoptosis resulting after 20 than 5 Gy, and occurred predominantly at 72 h post-irradiation. Microarray analysis showed associated dose-dependant apoptotic gene regulation changes. Western blotting revealed p53 up-regulation of at 72 h and phosphorylation at 3, 24, 48 and 72 h after irradiation. Early activation of c-jun occurred at 3 h, but was not sustained with time. Associated dose-dependant intracellular generation of reactive oxygen species (ROS) was also demonstrated using 2′ 7′-dichlorofluorescein diacetate. In conclusion, this study demonstrated a dose-dependant cochlear cell apoptosis and associated ROS generation after irradiation, with p53 possibly playing a key role. Based on this ROS-linked apoptotic model, anti-oxidants and anti-apoptotic factors could potentially be used to prevent radiation-induced sensori-neural hearing loss. As these medications can be delivered topically through the middle ear, their systematic side effects could therefore be minimized.

Keywords

Cell death Deafness Hair-cell Hearing loss Ototoxicity Radiotherapy 

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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Wong-Kein Low
    • 1
  • Michelle G. K. Tan
    • 2
  • Li Sun
    • 2
  • Alvin W. C. Chua
    • 3
  • Lip-Kai Goh
    • 1
  • De-Yun Wang
    • 4
  1. 1.Departments of OtolaryngologySingapore General HospitalSingaporeSingapore
  2. 2.Clinical ResearchSingapore General HospitalSingaporeSingapore
  3. 3.Plastic Reconstructive & Aesthetic SurgerySingapore General HospitalSingaporeSingapore
  4. 4.Department of OtolaryngologyNational University of SingaporeSingaporeSingapore

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