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Modulation of epithelial cell proliferation in culture by dissolved oxygen
Author(s) -
Taylor William C.,
Camalier Richard F.
Publication year - 1982
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041110105
Subject(s) - modulation (music) , microbiology and biotechnology , cell growth , cell culture , oxygen , chemistry , cell , biology , biophysics , biochemistry , genetics , physics , organic chemistry , acoustics
Modulation of epithelial cell proliferation by the dissolved oxygen concentration (P O 2 ) of the growth medium was assessed with primary human foreskin epithelium and a continuous monkey kidney epithelial cell line (LLC‐MK 2 ). Direct measurement of the growth medium P O 2 provides the first quantitative evaluation of epithelial cell proliferation as a function of P O 2 provides the first quantitative evaluation of epithelial cell proliferation as a function of P O 2 . Sustained proliferation of LLC‐MK 2 cells occurs in serum‐free medium equilibrated with a gas phase containing 18% or 30% O 2 v/v. Mid‐logarithmic phase cultures rapidly consume dissolved oxygen; this results in a 60–70 mm Hg decline in P O 2 and leads to a stable growth medium P O 2 between 70 and 100 mm Hg, well above anoxic values. In contrast, if culture medium is equilibrated with a gas phase containing 0% or 1% O 2 v/v to yield a growth medium P O 2 ∼ 20–40 mm Hg, proliferation of LLC‐MK 2 and primary foreskin epithelial cells is retarded, and LLC‐MK 2 cells use little dissolved oxygen. Gentle, continuous rocking to prevent diffusion gradient formation enhances proliferation slightly at the higher P O 2 , but neither periodic fluid renewals nor continued rocking stimulates cells retarded by a lowered oxygen concentration to resume proliferation. The data collectively demonstrate that epithelial cell proliferation requires a P O 2 > 40 mm Hg, and threshold requirements are probably closer to 70 mm Hg. Glycolysis continues at a P O 2 insufficient for proliferation, but more lactic acid accumulates in actively proliferating cultures than in cultures equilibrated with 0% oxygen. We conclude that epithelial cells in vitro both consume more oxygen and require a higher P O 2 for continued proliferation, and that the oxygen requirement for epithelial cell proliferation exceeds that of a comparable population of fibroblasts for which low oxygen may enhance survival and proliferation.