title: HEI-OC1 cells as a model for investigating drug cytotoxicity.
abstract: The House Ear Institute-Organ of Corti 1 (HEI-OC1) is one of the few, and arguable the most used, mouse auditory cell line available for research purposes. Originally proposed as an in vitro system for screening of ototoxic drugs, it has been used to investigate, among other topics, apoptotic pathways, autophagy and senescence, mechanism of cell protection, inflammatory responses, cell differentiation, effects of hypoxia, oxidative and endoplasmic reticulum stress, and expression of molecular channels and receptors. However, the use of different techniques with different goals resulted in apparent contradictions on the actual response of these cells to some specific treatments. We have now performed studies to characterize the actual response of HEI-OC1 cells to a battery of commonly used pharmacological drugs. We evaluated cell toxicity, apoptosis, viability, proliferation, senescence and autophagy in response to APAP (acetaminophen), cisplatin, dexamethasone, gentamicin, penicillin, neomycin, streptomycin, and tobramycin, at five different doses and two time-points (24 and 48 h), by flow cytometry techniques and caspase 3/7, MTT, Cytotoxicity, BrdU, Beclin1, LC3 and SA-β-galactosidase assays. We also used HEK-293 and HeLa cells to compare some of the responses of these cells to those of HEI-OC1. Our results indicate that every cell line responds to the each drug in a different way, with HEI-OC1 cells showing a distinctive sensitivity to at least one of the mechanisms under study. Altogether, our results suggest that the HEI-OC1 might be a useful model to investigate biological responses associated with auditory cells, including auditory sensory cells, but a careful approach would be necessary at the time of evaluating drug effects.
authors.affiliation: Laboratory of Auditory Cell Biology, Department of Head & Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Gilda
authors.initials: G
authors.lastname: Kalinec
authors.affiliation: Laboratory of Auditory Cell Biology, Department of Head & Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Pru
authors.initials: P
authors.lastname: Thein
authors.affiliation: Laboratory of Auditory Cell Biology, Department of Head & Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Channy
authors.initials: C
authors.lastname: Park
authors.affiliation: Laboratory of Auditory Cell Biology, Department of Head & Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Electronic address: fkalinec@mednet.ucla.edu.
authors.forename: Federico
authors.initials: F
authors.lastname: Kalinec
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D016922:Cellular Senescence; D002945:Cisplatin / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005839:Gentamicins / Q000494:pharmacology; D057809:HEK293 Cells; D006198:Hair Cells, Auditory / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009355:Neomycin / Q000494:pharmacology; D009925:Organ of Corti / Q000166:cytology; D010406:Penicillins / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013307:Streptomycin / Q000494:pharmacology; D014031:Tobramycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D005839:Gentamicins; D010406:Penicillins; D017382:Reactive Oxygen Species; D003907:Dexamethasone; D009355:Neomycin; D002945:Cisplatin; D014031:Tobramycin; D013307:Streptomycin
keywords: Autophagy; Cell death; Cell senescence; Cell viability; Cytotoxicity; HEI-OC1 cells; HEK-293 cells; HeLa cells