Cochlear damage and increased threshold in alpha-difluoromethylornithine (DFMO) treated guinea pigs

Abstract

Alpha-difluoromethylornithine (DFMO) inhibits polyamine synthesis and is used as an antineoplastic and antiparasitic drug. In early human trials DFMO unexpectedly caused a sensorineural hearing loss. In the current study DFMO was administered to guinea pigs to investigate its effects on organ of Corti histology and on auditory thresholds. Histologic examination revealed that DFMO caused greatest damage in the hook and first turn. Damage in the second and third turns was minimal. Animals treated for 12 weeks with DFMO differed significantly ( P < 0.05) from controls in the hook and first turn in that: 1) DFMO caused a loss of hair cells in all rows. Loss of inner hair cells was greater than that of outer hair cells. 2) The remaining outer hair cells were shorter and contained a greater number of Hensen bodies. 3) The Deiters' cell bodies were longer and this increased length was associated with the decreased length of the corresponding outer hair cells. Brainstem audiometry showed that DFMO produced a hearing loss and the magnitude of this loss increased over twelve weeks of DFMO administration.