title: Cytotoxicity and mitogenicity assays with real-time and label-free monitoring of human granulosa cells with an impedance-based signal processing technology intergrating micro-electronics and cell biology.
abstract: A recently developed technology (xCelligence) integrating micro-electronics and cell biology allows real-time, uninterrupted and quantitative analysis of cell proliferation, viability and cytotoxicity by measuring the electrical impedance of the cell population in the wells without using any labeling agent. In this study we investigated if this system is a suitable model to analyze the effects of mitogenic (FSH) and cytotoxic (chemotherapy) agents with different toxicity profiles on human granulosa cells in comparison to conventional methods of assessing cell viability, DNA damage, apoptosis and steroidogenesis. The system generated the real-time growth curves of the cells, and determined their doubling times, mean cell indices and generated dose-response curves after exposure to cytotoxic and mitogenic stimuli. It accurately predicted the gonadotoxicity of the drugs and distinguished less toxic agents (5-FU and paclitaxel) from more toxic ones (cisplatin and cyclophosphamide). This platform can be a useful tool for specific end-point assays in reproductive toxicology.
authors.affiliation: Koc University School of Medicine Department of Obstetrics and Gynecology, Istanbul, Turkey; American Hospital Women's Health Center, Assisted Reproduction Unit, Istanbul, Turkey. Electronic address: ooktem@ku.edu.tr.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Oktem
authors.affiliation: Koc University School of Medicine and the Graduate School of Health Sciences, Istanbul, Turkey.
authors.forename: Gamze
authors.initials: G
authors.lastname: Bildik
authors.affiliation: Koc University School of Medicine and the Graduate School of Health Sciences, Istanbul, Turkey.
authors.forename: Filiz
authors.initials: F
authors.lastname: Senbabaoglu
authors.affiliation: Koc University School of Medicine and the Graduate School of Health Sciences, Istanbul, Turkey.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Lack
authors.affiliation: Koc University School of Medicine and the Graduate School of Health Sciences, Istanbul, Turkey.
authors.forename: Nazli
authors.initials: N
authors.lastname: Akin
authors.affiliation: American Hospital Women's Health Center, Assisted Reproduction Unit, Istanbul, Turkey.
authors.forename: Feridun
authors.initials: F
authors.lastname: Yakar
authors.affiliation: Koc University School of Medicine and the Graduate School of Health Sciences, Istanbul, Turkey.
authors.forename: Defne
authors.initials: D
authors.lastname: Urman
authors.affiliation: American Hospital Women's Health Center, Assisted Reproduction Unit, Istanbul, Turkey.
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Guzel
authors.affiliation: American Hospital Women's Health Center, Assisted Reproduction Unit, Istanbul, Turkey.
authors.forename: Basak
authors.initials: B
authors.lastname: Balaban
authors.affiliation: Nagoya University School of Medicine Department of Obstetrics and Gynecology, Nagoya, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Iwase
authors.affiliation: Koc University School of Medicine Department of Obstetrics and Gynecology, Istanbul, Turkey; American Hospital Women's Health Center, Assisted Reproduction Unit, Istanbul, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Urman
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay / Q000379:methods*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage; D017097:Electric Impedance; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008934:Mitogens / Q000633:toxicity*; D011374:Progesterone / Q000378:metabolism; D012815:Signal Processing, Computer-Assisted; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D008934:Mitogens; D011374:Progesterone; D004958:Estradiol
keywords: Chemotherapy; Cytotoxicity; Human granulosa cells; Mitogenicity; xCelligence