Application of a continuous bioreactor cascade to study the effect of linoleic acid on hybridoma cell physiology

D. Kisztelinski, G.M. Alink, I.M.C.M. Rietjens, S. Bielecki, J. Tramper, D.E. Martens

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

The aim of the present study is to demonstrate the use of controlled bioreactors for toxicological studies. As a model system the effect of linoleic acid on hybridoma cells is studied in two well-controlled continuously operated bioreactors placed in series. In the first reactor the effect on rapid proliferating cells can be studied, while in the second reactor a special steady state is created, which allows studying the effect on apoptotic cells. Experiments are done at 0, 25, and 50 microM linoleic acid. At the end of the experiment with 50 microM linoleic acid, the concentration of linoleic acid is increased stepwise to determine the cytotoxic level. For rapid proliferating cells exposed to 25 and 50 microM stimulation of growth was observed. At 50 microM there was at the same time an increase in cell death through apoptosis. For stressed apoptotic cells linoleic acid caused partial growth inhibition at 25 and 50 microM and arrest of cell proliferation in the G(2)/M phase at 50 microM. For both, rapid proliferating cells and stressed apoptotic cells, complete growth inhibition occurred at 85 microM, with cells being arrested in the G(2)/M phase and dying mainly through necrosis. Cells in the bioreactor system appeared to be more sensitive towards linoleic acid than cells grown in multi-well plates. (IC(50) = 300 microM; IC(100) = 400 microM). Altogether the results of the present study reveal that the biostat experiments allow detailed analysis of the effect of a bioactive ingredient on cell physiology and behavior.
LanguageEnglish
Pages370-383
JournalBiotechnology and Bioengineering
Volume95
Issue number3
DOIs
Publication statusPublished - 2006

Fingerprint

Linoleic acid
Cell Physiological Phenomena
Physiology
Hybridomas
Bioreactors
Linoleic Acid
Cells
Cell death
Cell Division
Experiments
Cell proliferation
Growth
Apoptosis
Toxicology
Cell Death
Necrosis
Cell Proliferation

Keywords

  • polyunsaturated fatty-acids
  • human cancer-cells
  • arachidonic-acid
  • in-vitro
  • mammary tumorigenesis
  • eicosanoid synthesis
  • dilution rate
  • growth-rate
  • nude-mice
  • apoptosis

Cite this

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title = "Application of a continuous bioreactor cascade to study the effect of linoleic acid on hybridoma cell physiology",
abstract = "The aim of the present study is to demonstrate the use of controlled bioreactors for toxicological studies. As a model system the effect of linoleic acid on hybridoma cells is studied in two well-controlled continuously operated bioreactors placed in series. In the first reactor the effect on rapid proliferating cells can be studied, while in the second reactor a special steady state is created, which allows studying the effect on apoptotic cells. Experiments are done at 0, 25, and 50 microM linoleic acid. At the end of the experiment with 50 microM linoleic acid, the concentration of linoleic acid is increased stepwise to determine the cytotoxic level. For rapid proliferating cells exposed to 25 and 50 microM stimulation of growth was observed. At 50 microM there was at the same time an increase in cell death through apoptosis. For stressed apoptotic cells linoleic acid caused partial growth inhibition at 25 and 50 microM and arrest of cell proliferation in the G(2)/M phase at 50 microM. For both, rapid proliferating cells and stressed apoptotic cells, complete growth inhibition occurred at 85 microM, with cells being arrested in the G(2)/M phase and dying mainly through necrosis. Cells in the bioreactor system appeared to be more sensitive towards linoleic acid than cells grown in multi-well plates. (IC(50) = 300 microM; IC(100) = 400 microM). Altogether the results of the present study reveal that the biostat experiments allow detailed analysis of the effect of a bioactive ingredient on cell physiology and behavior.",
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author = "D. Kisztelinski and G.M. Alink and I.M.C.M. Rietjens and S. Bielecki and J. Tramper and D.E. Martens",
year = "2006",
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Application of a continuous bioreactor cascade to study the effect of linoleic acid on hybridoma cell physiology. / Kisztelinski, D.; Alink, G.M.; Rietjens, I.M.C.M.; Bielecki, S.; Tramper, J.; Martens, D.E.

In: Biotechnology and Bioengineering, Vol. 95, No. 3, 2006, p. 370-383.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Application of a continuous bioreactor cascade to study the effect of linoleic acid on hybridoma cell physiology

AU - Kisztelinski, D.

AU - Alink, G.M.

AU - Rietjens, I.M.C.M.

AU - Bielecki, S.

AU - Tramper, J.

AU - Martens, D.E.

PY - 2006

Y1 - 2006

N2 - The aim of the present study is to demonstrate the use of controlled bioreactors for toxicological studies. As a model system the effect of linoleic acid on hybridoma cells is studied in two well-controlled continuously operated bioreactors placed in series. In the first reactor the effect on rapid proliferating cells can be studied, while in the second reactor a special steady state is created, which allows studying the effect on apoptotic cells. Experiments are done at 0, 25, and 50 microM linoleic acid. At the end of the experiment with 50 microM linoleic acid, the concentration of linoleic acid is increased stepwise to determine the cytotoxic level. For rapid proliferating cells exposed to 25 and 50 microM stimulation of growth was observed. At 50 microM there was at the same time an increase in cell death through apoptosis. For stressed apoptotic cells linoleic acid caused partial growth inhibition at 25 and 50 microM and arrest of cell proliferation in the G(2)/M phase at 50 microM. For both, rapid proliferating cells and stressed apoptotic cells, complete growth inhibition occurred at 85 microM, with cells being arrested in the G(2)/M phase and dying mainly through necrosis. Cells in the bioreactor system appeared to be more sensitive towards linoleic acid than cells grown in multi-well plates. (IC(50) = 300 microM; IC(100) = 400 microM). Altogether the results of the present study reveal that the biostat experiments allow detailed analysis of the effect of a bioactive ingredient on cell physiology and behavior.

AB - The aim of the present study is to demonstrate the use of controlled bioreactors for toxicological studies. As a model system the effect of linoleic acid on hybridoma cells is studied in two well-controlled continuously operated bioreactors placed in series. In the first reactor the effect on rapid proliferating cells can be studied, while in the second reactor a special steady state is created, which allows studying the effect on apoptotic cells. Experiments are done at 0, 25, and 50 microM linoleic acid. At the end of the experiment with 50 microM linoleic acid, the concentration of linoleic acid is increased stepwise to determine the cytotoxic level. For rapid proliferating cells exposed to 25 and 50 microM stimulation of growth was observed. At 50 microM there was at the same time an increase in cell death through apoptosis. For stressed apoptotic cells linoleic acid caused partial growth inhibition at 25 and 50 microM and arrest of cell proliferation in the G(2)/M phase at 50 microM. For both, rapid proliferating cells and stressed apoptotic cells, complete growth inhibition occurred at 85 microM, with cells being arrested in the G(2)/M phase and dying mainly through necrosis. Cells in the bioreactor system appeared to be more sensitive towards linoleic acid than cells grown in multi-well plates. (IC(50) = 300 microM; IC(100) = 400 microM). Altogether the results of the present study reveal that the biostat experiments allow detailed analysis of the effect of a bioactive ingredient on cell physiology and behavior.

KW - polyunsaturated fatty-acids

KW - human cancer-cells

KW - arachidonic-acid

KW - in-vitro

KW - mammary tumorigenesis

KW - eicosanoid synthesis

KW - dilution rate

KW - growth-rate

KW - nude-mice

KW - apoptosis

U2 - 10.1002/bit.20897

DO - 10.1002/bit.20897

M3 - Article

VL - 95

SP - 370

EP - 383

JO - Biotechnology and Bioengineering

T2 - Biotechnology and Bioengineering

JF - Biotechnology and Bioengineering

SN - 0006-3592

IS - 3

ER -