Abstract
Chinese hamster ovary cells grown under conditions which are optimal for the production of a genetically engineered protein in batch culture, lose significant viability shortly after entering the stationary phase. This cell death was investigated morphologically and was found to be almost exclusively via apoptosi. Furthermore, cells were analyzed by flow cytometry using a fluorescent DNA end-labeling assay to label apoptotic cells, in conjunction with cell cycle analysis using propidium iodide. Apoptotic cells could be detected by this method, and by the radioactive end-labeling of extracted DNA, on all days of culture from day 1 to day 7; however, the degree of apoptotic cell death increased dramatically when the cells entered the stationary phase, rising to 50-60% of the total cell number at the termination of the culture. Flow cytometric analysis showed that the majority of cells underwent apoptosis whilst in G(1)/G(0) and formed an apoptotic population with high DNA FITC end-labeling and hypodiploid propidium iodide binding. Additionally, the ability or inability to secrete specific protein products did not appear to interfere with the development of the apoptotic population with time.
References
Oct 19, 1992·FEBS Letters·S el AlaouiM Griffin
Jan 1, 1992·Cytotechnology·J M Coco-MartinE C Beuvery
Jan 1, 1992·Cytotechnology·F FranĕkJ Dolníková
Jan 1, 1992·Cytometry·W G TelfordP J Fraker
Sep 1, 1991·Cell Proliferation·W G TelfordP J Fraker
Jan 1, 1991·International Review of Experimental Pathology·M J Arends, A H Wyllie
Dec 1, 1987·The Journal of Pathology·A H Wyllie
Feb 1, 1974·The Journal of Cell Biology·R Rodewald, M J Karnovsky
Aug 1, 1972·British Journal of Cancer·J F KerrA R Currie
Apr 10, 1980·Nature·A H Wyllie
Aug 25, 1982·Journal of Molecular Biology·R J Kaufman, P A Sharp
Oct 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·R C DukeJ J Cohen
Jul 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·G Urlaub, L A Chasin
Jan 1, 1980·International Review of Cytology·A H WyllieA R Currie
Jan 1, 1993·Cytotechnology·J L GoergenJ M Engasser
Aug 1, 1993·Endocrinology·R A Schwartzman, J A Cidlowski
Jan 1, 1993·Immunology Letters·T Vomastek, F Franĕk
Dec 20, 1989·Biotechnology and Bioengineering·E Suzuki, D F Ollis
Oct 5, 1991·Biotechnology and Bioengineering·D de la BroiseB Massie
Sep 5, 1994·Biotechnology and Bioengineering·R P SinghA N Emery
Nov 5, 1994·Biotechnology and Bioengineering·S Mercille, B Massie
Citations
Jul 9, 1999·Biotechnology and Bioengineering·S MercilleB Massie
Mar 4, 2000·Biotechnology and Bioengineering·B T TeyM Al-Rubeai
Sep 27, 2000·Biotechnology and Bioengineering·A SanfeliuG Stephanopoulos
Oct 29, 2002·Biotechnology and Bioengineering·Idsada Lengwehasatit, Alan J Dickson
Oct 16, 2002·Biotechnology and Bioengineering·Heiko MeentsMartin Fussenegger
Aug 20, 2011·Cytotechnology·Yi-Yun C WeiBrendan J McConkey
Jul 30, 2008·Cell Stress & Chaperones·Chaya Mohan, Gyun Min Lee
Apr 1, 1997·Current Opinion in Biotechnology·W S Hu, J G Aunins
May 20, 1998·Current Opinion in Biotechnology·M al-Rubeai, R P Singh
Oct 20, 2005·Journal of Bioscience and Bioengineering·Z YunT Yoshida
Jan 1, 1997·Cytotechnology·A MooreT Ryll
Jan 1, 1997·Cytotechnology·R P SinghM Al-Rubeai
Nov 13, 2008·Cytotechnology·M FusseneggerR Pörtner
Jun 30, 2005·Biotechnology and Bioengineering·Gisela G Chiang, William P Sisk
Oct 24, 2003·Biotechnology and Bioengineering·Simone M SchatzFriedrich Scheiflinger
Sep 16, 2014·Biotechnology and Bioengineering·Sarah M MercierMathieu Streefland
Jul 9, 1999·Biotechnology and Bioengineering·J A ZanghiJ E Bailey
Feb 10, 1999·Biotechnology and Bioengineering·J GoswamiD I Wang
Dec 31, 2003·The Journal of Biological Chemistry·Patrick RossignolEduardo Anglés-Cano
Jan 14, 2020·Biotechnology and Bioengineering·Matthew N HenryVerónica S Martínez
May 31, 1996·The Journal of Biological Chemistry·R M PittiA Ashkenazi
Mar 5, 2020·Analytical and Bioanalytical Chemistry·Johannes MöllerUwe Jandt
Jul 9, 1999·Biotechnology and Bioengineering·H KaufmannJ E Bailey
Apr 1, 2015·Evolution; International Journal of Organic Evolution·Christen M Bossu, Thomas J Near
Aug 2, 2016·Engineering in Life Sciences·Qing JiangGuanxin Shen