title: A cochlear cell line as an in vitro system for drug ototoxicity screening.
abstract: Aminoglycoside antibiotics, loop diuretics, antineoplastic agents and other commonly used pharmacological drugs are ototoxic. Understanding of the cellular and molecular mechanisms underlying drug ototoxicity, however, has been hampered by the limited availability of inner ear tissues and drug side effects on laboratory animals. Immortalized cell lines derived from the auditory sensory organ, sensitive to ototoxic drugs and growing in environments that can be systematically manipulated, would facilitate the research directed at elucidating these mechanisms. Such immortalized cell lines could also be used to discover novel therapeutic agents for preventing drug-induced sensorineural hearing loss. Here, we report a conditionally immortalized organ of Corti-derived epithelial cell line, which shows evidence of activation of apoptosis when exposed to known ototoxic drugs. This cell line may be an excellent in vitro system to investigate the cellular and molecular mechanisms involved in ototoxicity and for screening of the potential ototoxicity or otoprotective properties of new pharmacological drugs.
authors.affiliation: Section on Cell Structure and Function, Department of Cell and Molecular Biology, House Ear Institute, Los Angeles, California 90057, USA.
authors.forename: Gilda M
authors.initials: GM
authors.lastname: Kalinec
authors.forename: Paul
authors.initials: P
authors.lastname: Webster
authors.forename: David J
authors.initials: DJ
authors.lastname: Lim
authors.forename: Federico
authors.initials: F
authors.lastname: Kalinec
mesh_terms: D000617:Aminoglycosides; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D015415:Biomarkers; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D003051:Cochlea / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D015834:Cochlear Diseases / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D008403:Mass Screening; D051379:Mice; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D017468:Receptors, Fibroblast Growth Factor; D066246:ErbB Receptors; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases