THE SPECIFIC AMINO ACID REQUIREMENTS OF A HUMAN CARCINOMA CELL (STRAIN H E L A) IN TISSUE CULTURE
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The amino acid requirements of a human uterine carcinoma cell (HeLa strain) have been defined. The 12 compounds previously found to be essential for the growth of a mouse fibroblast proved similarly essential for this human epithelial cell. They included arginine, cyst(e)ine, histidine, and tyrosine, in addition to the eight amino acids required for nitrogen balance in man (isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine). Only the L-amino acids were active; the D-enantiomorphs had no demonstrable effect at physiologic concentrations. The minimum concentrations required for survival and limited growth varied from 0.003 µM per ml. for L-tryptophan, to 0.1 µM per ml. for L-lysine. The concentrations permitting optimum growth similarly varied from 0.01 µM per ml. for tryptophan, to 0.1 µM per ml. for leucine, isoleucine, threonine, lysine, and valine. The latter optimum concentrations of the individual amino acids were closely correlated with their serum levels. With at least six of the amino acids, high concentrations, in the range 1 to 10 µM per ml., caused a definite growth inhibition. In the absence of a single essential amino acid, degenerative changes occurred in the cells, culminating in their death and dissolution. In the early stages, however, these degenerative changes could be reversed by the restoration of the missing component.
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Cancer cells proliferating in vitro consume glutamine far in excess of any other amino acid and are often dependent on extracellular glutamine for survival.
“Glutamine is a non-essential amino acid, and yet cancer cells proliferating in vitro consume glutamine far in excess of any other amino acid and are often dependent on extracellular glutamine for survival (DeBerardinis and Cheng, 2010; Eagle, 1955; Jain et al., 2012).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Eagle, 1955
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THE FREE AMINO ACIDS OF HUMAN BLOOD PLASMA
Stein, W. H., & Moore, S. (1954) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)71179-4 · Cited by 935 · see citing works
STUDIES ON THE PROPAGATION IN VITRO OF POLIOMYELITIS VIRUSES
Scherer, W. F., Syverton, J. T., & Gey, G. O. (1953) · Journal of Experimental Medicine · doi:10.1084/jem.97.5.695 · Cited by 856 · see citing works
Culture Flasks for Use with Plane Surface Substrate Tissue Cultures
Earle, W. R., & Highhouse, F. (1954) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/14.4.841 · Cited by 10 · see citing works
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Nutrition Needs of Mammalian Cells in Tissue Culture
Eagle, H. (1955) · Science · doi:10.1126/science.122.3168.501 · Cited by 1,619 · see citing works
Self-citationTargeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971 · see citing works
Characteristics of an assay for Rous sarcoma virus and Rous sarcoma cells in tissue culture
Temin, H. M., & Rubin, H. (1958) · Virology · doi:10.1016/0042-6822(58)90114-4 · Cited by 554 · see citing works
The growth response of mammalian cells in tissue culture to L-glutamine and L-glutamic acid
Eagle, H., Oyama, V. I., Levy, M., Horton, C. L., & Fleischman, R. (1956) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)65826-0 · Cited by 354 · see citing works
Self-citationGoetzman, E. S., & Prochownik, E. V. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00129 · Cited by 199 · see citing works
The control of cellular morphology in embryonic cells infected with Rous sarcoma virus in vitro
Temin, H. M. (1960) · Virology · doi:10.1016/0042-6822(60)90038-6 · Cited by 186 · see citing works
- Authors
- Eagle, H.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Eagle, Harry
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1955-07-01
- Volume
- 102
- Issue
- 1
- Pages
- 37-48
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2136494
- OpenAlex
- W1971595342
- Cited by
- 336
- References
- 3
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 14 · 2023: 8 · 2022: 10 · 2021: 11 · 2020: 14 · 2019: 9 · 2018: 4 · 2017: 8 · 2016: 2 · 2015: 6 · 2014: 7 · 2013: 2 · 2012: 2
- FWCI
- 14.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- amino acid requirements, HeLa cells, essential amino acids, L-amino acids, D-amino acids, serum amino acids, cell growth, cell death, epithelial cell culture
- MeSH terms
- Amino Acids, Animals, Arginine, Coloring Agents, Female, HeLa Cells, Histidine, Humans, Isoleucine, Leucine, Lysine, Methionine, Neoplasms, Experimental, Phenylalanine, Threonine, Tryptophan, Tyrosine, Uterine Neoplasms, Uterus, Valine, Tissue Culture Techniques, Mice
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