R429 – Irradiation Changes MyHC Expression in Rat Larynx

Abstract

Problem Laryngeal cancer treatment involves radiotherapy, laser treatment, and/or surgery. Radiotherapy does not impair voice quality as much as laser treatment or surgery but can induce muscle wasting, fibrosis, and dry mouth symptoms. To elucidate the molecular mechanisms involved in such changes, we investigated the effect of irradiation on myosin heavy chain (MyHC) expression in laryngeal muscles. Methods Rats were irradiated with one dose of 10, 15, 20, 25, 30, or 35 Gy and sacrificed 2 weeks later. Other rats were irradiated with 20 Gy and sacrificed 3 days or 2, 4, or 12 weeks later. The thyroarytenoid (TA), posterior cricoarytenoid (PCA), cricothyroid (CT), and digastric (DG) muscles were subjected to SYBR Green real time-reverse transcriptase-PCR. Results Radiation exceeding 20 Gy killed all rats within 7-12 days. Two weeks after irradiation with 10, 15, or 20 Gy, MyHC type IIa expression had decreased in a dose-dependent manner in the PCA and CT muscles and in a dose-independent manner in the TA muscle. The expression of MyHC IIx and IIL also decreased but in a dose-dependent manner in the TA muscle and a dose-independent manner in the PCA and CT muscles. In the 20 Gy-irradiated rats, MyHC IIx, IIL, and especially IIa expression declined over 12 weeks. Conclusion The laryngeal muscles responded differently to radiation but showed a time-dependent and long-lasting decrease in the expression of all MyHC isoforms. MyHC IIa expression in the PCA and CT muscles may be more sensitive to irradiation than the other MyHC isoforms. Significance All of these observations together support the notion that if the radiation-induced changes in MyHC expression in the larynx can be ameliorated by an as-yet undefined method, it may be possible to restore to normal the laryngeal muscles of larynx cancer patients who have been trated with radiation therapy, therepy presevering their voice quality. Support This work was supported by the Korea Research Foundation Grant funded by the Korea Govement (MOE-HRD)” (KRF-2006-331-E00235).