The ototoxicity of carboplatin, a second generation anti-cancer agent,
was examined using the chinchilla as an animal model. In animals trea
ted with a clinical therapeutic dose (400 mg/m(2)), the dominant degen
erative change is to inner hair cells (IHCs). This is in sharp contras
t to most other ototoxic agents, which damage primarily the outer hair
cells (OHCs). Functional changes to the cochlea have been evaluated i
n carboplatin treated subjects by recording cochlear action potentials
(CAP) and cochlear microphonics (CM); cochlear lesions were evaluated
using scanning electron microscopy. In carboplatin treated animals, C
AP thresholds to tone-pip stimuli were elevated in proportion to IHC d
amage in corresponding cochlear regions. In contrast, CM amplitudes an
d 'thresholds' remained close to normal in most cases, reflecting the
preservation of OHCs in the basal turn. These results indicate a high
degree of independence between the inner and outer hair cell systems i
n the cochlear transduction mechanism. We suggest that this species-sp
ecific preparation with selective IHC loss will provide a valuable too
l for studying, separately, the role of OHCs in both afferent and effe
rent cochlear function.