Topical application of mitomycin C to the middle ear is ototoxic in the gerbil.
OBJECTIVE
Mitomycin C is ototoxic when applied topically to the structures of the middle ear.


BACKGROUND
Mitomycin C is a topically applied medication widely used in a variety of surgical procedures to prevent excessive scar tissue formation. Its safety for use during otologic procedures has not been fully evaluated.


METHODS
A laboratory study was undertaken using the Mongolian gerbil as an animal model. Both acute and chronic effects on cochlear function of mitomycin C were assessed with measurements of compound action potential (CAP) thresholds of the auditory nerve, CAP input/output functions, distortion product otoacoustic emissions, and endocochlear potentials. Morphologic changes were assessed with light microscopy using hematoxylin-eosin staining as well as transmission electron microscopy.


RESULTS
Five-minute applications of mitomycin C (0.5 mg/ml) to the entire surface of the middle ear adversely affected CAP thresholds, input/output functions, distortion product otoacoustic emissions, and the endocochlear potential. Ninety-minute exposures of mitomycin C solely to the round window produced similar changes. Histologic evaluation of animals 1 week after treatment showed damage to cochlear hair cells, the stria vascularis, and spiral ganglion neurons when compared with controls.


CONCLUSIONS
Mitomycin C can produce substantial sensorineural hearing loss when applied topically to the gerbil middle ear for even brief periods. Consequently, its safety for topical use in the human middle ear is highly questionable.
Moody
Marcus W
MW
Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina 29425, USA. moodym@musc.edu
Lang
Hainan
H
Spiess
Adam C
AC
Smythe
Nancy
N
Lambert
Paul R
PR
Schmiedt
Richard A
RA
D000200:Action Potentials / Q000187:drug effects; D000287:Administration, Topical; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001300:Audiometry, Evoked Response; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D004432:Ear, Middle / Q000187:drug effects*; D005260:Female; D005849:Gerbillinae; D008297:Male; D046529:Microscopy, Electron, Transmission; D016685:Mitomycin / Q000633:toxicity*; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D016685:Mitomycin