In vivo and in vitro models of ionizing radiation to the vocal folds.
BACKGROUND
Radiation therapy (RT) to the head and neck often results in damage to the vocal folds (VF) and surrounding structures. Characterization and treatment of these sequelae is limited, likely due to the lack of experimental models.


METHODS
Larynges from rats exposed to 2 fractionation schedules (40 Gy total) were analyzed histologically. In vitro, reactive oxygen species (ROS) synthesis, and transcription of select genes associated with ROS, inflammation, and fibrosis were examined in VF fibroblasts after single-dose radiation.


RESULTS
Although radiation-induced histologic alterations are made to VF architecture, 1 fractionation schedule was accompanied by significant morbidity and mortality. In vitro, radiation increased ROS synthesis and inflammatory and profibrotic gene expression.


CONCLUSIONS
Our data suggest that hyperfractionated RT is more tolerable. Utilizing this model, RT-induced histologic aberrations are made to the VF mucosa. In addition, a relationship between radiation, ROS, and inflammatory and fibrotic gene expression was observed in vitro.
Saltman
Benjamin
B
Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, USA.
Kraus
Dennis H
DH
Szeto
Hazel
H
Parashar
Bhupesh
B
Ghossein
Ronald
R
Felsen
Diane
D
Branski
Ryan C
RC
D000505:Alopecia / Q000209:etiology; D000818:Animals; D003681:Dehydration / Q000209:etiology; D019583:Dose Fractionation, Radiation; D004890:Erythema / Q000209:etiology; D005355:Fibrosis; D051547:Heme Oxygenase-1 / Q000235:genetics; D006984:Hypertrophy; D066298:In Vitro Techniques; D007820:Laryngeal Mucosa / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D023421:Models, Animal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012883:Skin Ulcer / Q000209:etiology; D016212:Transforming Growth Factor beta / Q000235:genetics; D014827:Vocal Cords / Q000473:pathology* / Q000528:radiation effects*; D015431:Weight Loss
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D051547:Heme Oxygenase-1; D020781:Matrix Metalloproteinase 1