{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T06:31:26Z","timestamp":1782801086321,"version":"3.54.5"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,5,21]],"date-time":"2002-05-21T00:00:00Z","timestamp":1021939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2002,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>B\u2010cell hybridomas are widely used to produce monoclonal antibodies via large\u2010scale cell culture. Unfortunately, these cells are highly sensitive to apoptotic death under conditions of nutrient deprivation observed at the plateau phase of batch cultures. Previous work has indicated that constitutive high\u2010level expression of antiapoptotic genes in hybridoma cells could delay apoptosis, resulting in higher cell densities and prolonged viability. However, the constitutive high\u2010level expression of antiapoptotic genes has been shown to have detrimental effects on genomic stability of other types of cultured cells. Inducible gene expression may be used to avoid this problem. In the present study, we first constructed an expression vector in which the promoter of a mammalian metallothionein (MT) gene drives the expression of <jats:italic>bcl\u2010X<jats:sub>L<\/jats:sub><\/jats:italic> in response to metal exposure. The vector was then used to exogenously control the expression of <jats:italic>bcl\u2010X<jats:sub>L<\/jats:sub><\/jats:italic> in D5 hybridoma cells. Our data show that stably transfected D5 cells (4G1.D9) expressed high levels of Bcl\u2010X<jats:sub>L<\/jats:sub> following overnight exposure to ZnSO<jats:sub>4<\/jats:sub> concentrations (50 to 100 \u03bc<jats:italic>M<\/jats:italic>) that did not affect control cells. The level of Bcl\u2010X<jats:sub>L<\/jats:sub> expressed after ZnSO<jats:sub>4<\/jats:sub> induction was sufficient to prevent apoptosis experimentally induced by cycloheximide and allowed 4G1.D9 cells to grow at higher densities and remain viable for prolonged periods in suboptimal culture conditions. The use of inducible <jats:italic>bcl\u2010X<jats:sub>L<\/jats:sub><\/jats:italic> expression permits extension of the viability of cultured B\u2010cell hybridomas during the antibody secretion phase without the adverse genetic effects associated with constitutive long\u2010term <jats:italic>bcl\u2010X<jats:sub>L<\/jats:sub><\/jats:italic> expression. \u00a9 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 180\u2013187, 2002.<\/jats:p>","DOI":"10.1002\/bit.10279","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T08:21:52Z","timestamp":1033892512000},"page":"180-187","source":"Crossref","is-referenced-by-count":29,"title":["Inducible expression of Bcl\u2010X<sub>L<\/sub> restricts apoptosis resistance to the antibody secretion phase in hybridoma cultures"],"prefix":"10.1002","volume":"79","author":[{"given":"Daniel","family":"Jung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"C\u00f4t\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Drouin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Simard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9al","family":"Lemieux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,5,21]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90508-N"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008186302600"},{"key":"e_1_2_1_4_1","first-page":"1489","article-title":"Suppression of apoptosis by Bcl\u20102 or Bcl\u2010xL promotes susceptibility to mutagenesis","volume":"13","author":"Cherbonnel\u2010Lasserre C","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260380712"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(90)90379-A"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1993.1189"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90123-T"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/374731a0"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007914619219"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00369579"},{"key":"e_1_2_1_12_1","first-page":"1451","article-title":"Role of bcl\u2010X(L) in the control of apoptosis in murine myeloma cells","volume":"56","author":"Gauthier ER","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(98)00166-5"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-5993-1_9"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.4049\/jimmunol.141.5.1624","article-title":"Characterization of higher avidity monoclonal antibodies produced by murine B\u2010cell hybridoma variants selected for increased antigen binding of membrane Ig","volume":"141","author":"Martel F","year":"1988","journal-title":"J Immunol"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0290(20000220)67:4<435::AID-BIT7>3.0.CO;2-Y"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260430902"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0290(19990605)63:5<516::AID-BIT2>3.0.CO;2-9"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00762386"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.20.2621"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.5.1903.bloodjournal8651903"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0290(19960805)51:3<298::AID-BIT5>3.0.CO;2-8"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90509-O"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041560210"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00749936"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.124.1.1"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260420405"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0290(19961005)52:1<166::AID-BIT17>3.0.CO;2-M"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.71.3.1739-1746.1997"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007954103572"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2478(93)90142-O"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90411-5"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/352345a0"}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbit.10279","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.10279","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:06:28Z","timestamp":1760040388000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.10279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,5,21]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2002,7,20]]}},"alternative-id":["10.1002\/bit.10279"],"URL":"https:\/\/doi.org\/10.1002\/bit.10279","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"value":"0006-3592","type":"print"},{"value":"1097-0290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,5,21]]}}}