title: The influence of bisphenol A on mammalian cell cultivation.
abstract: Bisphenol A (BPA) plays a substantial role in industry, as it is used for polycarbonate (PC) plastics and epoxy resins which are required for various plastic consumer products. However, BPA is known to be an endocrine disruptor, and its influence on humans, animals, and various cell lines was addressed in diverse studies. As the burden of BPA can be increased by using disposable plastic articles and single-use technologies for cultivation, it is essential to examine the consequences of BPA presence on mammalian cells, as they are a contributing factor in the production of complex pharmaceutical therapeutics. We selected three industrially relevant cell lines and analyzed systemic effects of BPA by comparing cell culture performance in BPA-free poly-ethylene terephthalate glycol (PETG) and in PC shaking flasks. We focused on the influence of BPA on cellular growth, viability, and several metabolic parameters. In addition, we determined the product concentration and aggregation behavior of the recombinant proteins expressed by these cell lines and the BPA concentration within the medium caused by leaching. Moreover, we performed EC50 studies to determine the toxic concentration of BPA. Our results indicated that leached BPA had no effect on specific growth rates and viability and toxicity appeared at about 10(4) times higher concentrations; however, it influenced the specific productivity rate and metabolic activity parameters of our Chinese hamster ovary (CHO) cell line. Consequently, one can neglect BPA from leaching in the culture as long as the selected cell line is BPA tolerant. Otherwise, BPA can be a hurdle for pharmaceutical production, as it can influence the specific productivity of recombinant proteins.
authors.affiliation: Institute of Applied Biotechnology, University of Applied Sciences Biberach, Hubertus-Liebrecht-Strasse 35, 88400, Biberach, Germany.|Faculty of Medicine, University of Ulm, Albert-Einstein-Allee 11, 89079, Ulm, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Stiefel
authors.affiliation: Institute of Applied Biotechnology, University of Applied Sciences Biberach, Hubertus-Liebrecht-Strasse 35, 88400, Biberach, Germany.
authors.forename: Albert Jesuran
authors.initials: AJ
authors.lastname: Paul
authors.affiliation: Napoli Laboratorio Chimico Merceologico, Az. Spec. CCIAA of Naples, Corso Meridionale, 58, Naples, Italy.
authors.forename: Troisi
authors.initials: T
authors.lastname: Jacopo
authors.affiliation: Napoli Laboratorio Chimico Merceologico, Az. Spec. CCIAA of Naples, Corso Meridionale, 58, Naples, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Sgueglia
authors.affiliation: Institute of Applied Biotechnology, University of Applied Sciences Biberach, Hubertus-Liebrecht-Strasse 35, 88400, Biberach, Germany.|Faculty of Medicine, University of Ulm, Albert-Einstein-Allee 11, 89079, Ulm, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Stützle
authors.affiliation: Institute of Applied Biotechnology, University of Applied Sciences Biberach, Hubertus-Liebrecht-Strasse 35, 88400, Biberach, Germany. herold@hochschule-bc.de.
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Herold
authors.affiliation: Institute of Applied Biotechnology, University of Applied Sciences Biberach, Hubertus-Liebrecht-Strasse 35, 88400, Biberach, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Hesse
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000378:metabolism* / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004968:Estrogens, Non-Steroidal / Q000378:metabolism* / Q000633:toxicity; D010636:Phenols / Q000378:metabolism* / Q000633:toxicity; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003470:Culture Media; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Cell culture; Leachables; Product quality