Abstract
1) Both the growth rate and the maximum population density of several normal, virus-transformed, and cancer cells were markedly pH-dependent; the optimum varied from pH 6.9 to 7.8. At the optimum pH, some diploid human cells attained population densities comparable to those of cancer or virus-transformed cells. Contact inhibition of growth is facilitated by repeated fluctuations of pH in nonphysiological ranges, and may not be an intrinsic and necessary attribute of diploid cells in culture. 2) At pH 8.3, at which there was little or no cellular multiplication, the protein content per cell increased 2- to 5-fold over a period of 10-16 days, and was slowly reversed to normal concentrations on restoration of pH to the optimal range. 3) Uridine uptake by contact-inhibited human cell cultures was stimulated by refeeding with salt solution, and to the same extent as by complete (serum-supplemented) growth medium; that immediate increase did not involve the reinitiation of cellular growth and multiplication. Contact inhibition was, however, reversed in 2-4 days by an appropriate increase in the serum concentration of the medium.
Full text
PDF![229](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b71/391201/119cccb75896/pnas00076-0236.png)
![230](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b71/391201/14f6cb48efd8/pnas00076-0237.png)
![231](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b71/391201/a6a41bdaeec1/pnas00076-0238.png)
![232](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b71/391201/82257e3a38bc/pnas00076-0239.png)
![233](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b71/391201/505f04ebbd1a/pnas00076-0240.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cunningham D. D., Pardee A. B. Transport changes rapidly initiated by serum addition to "contact inhibited" 3T3 cells. Proc Natl Acad Sci U S A. 1969 Nov;64(3):1049–1056. doi: 10.1073/pnas.64.3.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- EAGLE H. Amino acid metabolism in mammalian cell cultures. Science. 1959 Aug 21;130(3373):432–437. doi: 10.1126/science.130.3373.432. [DOI] [PubMed] [Google Scholar]
- EAGLE H. The specific amino acid requirements of a human carcinoma cell (Stain HeLa) in tissue culture. J Exp Med. 1955 Jul 1;102(1):37–48. doi: 10.1084/jem.102.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eagle H., Foley G. E., Koprowski H., Lazarus H., Levine E. M., Adams R. A. Growth characteristics of virus-transformed cells. Maximum population density, inhibition by normal cells, serum requirement, growth in soft agar, and xenogeneic transplantability. J Exp Med. 1970 Apr 1;131(4):863–879. doi: 10.1084/jem.131.4.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eagle H., Levine E. M. Growth regulatory effects of cellular interaction. Nature. 1967 Mar 18;213(5081):1102–1106. doi: 10.1038/2131102a0. [DOI] [PubMed] [Google Scholar]
- HAYFLICK L. THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS. Exp Cell Res. 1965 Mar;37:614–636. doi: 10.1016/0014-4827(65)90211-9. [DOI] [PubMed] [Google Scholar]
- Holley R. W., Kiernan J. A. "Contact inhibition" of cell division in 3T3 cells. Proc Natl Acad Sci U S A. 1968 May;60(1):300–304. doi: 10.1073/pnas.60.1.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kruse P. F., Jr, Miedema E. Production and characterization of multiple-layered populations of animal cells. J Cell Biol. 1965 Nov;27(2):273–279. doi: 10.1083/jcb.27.2.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LEVINE E. M., BECKER Y., BOONE C. W., EAGLE H. CONTACT INHIBITION, MACROMOLECULAR SYNTHESIS, AND POLYRIBOSOMES IN CULTURED HUMAN DIPLOID FIBROBLASTS. Proc Natl Acad Sci U S A. 1965 Feb;53:350–356. doi: 10.1073/pnas.53.2.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levine E. M., Thomas L., McGregor D., Hayflick L., Eagle H. Altered nucleic acid metabolism in human cell cultures infected with mycoplasma. Proc Natl Acad Sci U S A. 1968 Jun;60(2):583–589. doi: 10.1073/pnas.60.2.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- OYAMA V. I., EAGLE H. Measurement of cell growth in tissue culture with a phenol reagent (folin-ciocalteau). Proc Soc Exp Biol Med. 1956 Feb;91(2):305–307. doi: 10.3181/00379727-91-22245. [DOI] [PubMed] [Google Scholar]
- Robbins E., Levine E. M., Eagle H. Morphologic changes accompanying senescence of cultured human diploid cells. J Exp Med. 1970 Jun 1;131(6):1211–1222. doi: 10.1084/jem.131.6.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shapiro A. L., Siegel I. M., Scharff M. D., Robbins E. Characteristics of cultured lens epithelium. Invest Ophthalmol. 1969 Aug;8(4):393–400. [PubMed] [Google Scholar]
- Siniscalco M., Klinger H. P., Eagle H., Koprowski H., Fujimoto W. Y., Seegmiller J. E. Evidence for intergenic complementation in hybrid cells derived from two human diploid strains each carrying an X-linked mutation. Proc Natl Acad Sci U S A. 1969 Mar;62(3):793–799. doi: 10.1073/pnas.62.3.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
- TODARO G. J., GREEN H. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol. 1963 May;17:299–313. doi: 10.1083/jcb.17.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Todaro G. J., Lazar G. K., Green H. The initiation of cell division in a contact-inhibited mammalian cell line. J Cell Physiol. 1965 Dec;66(3):325–333. doi: 10.1002/jcp.1030660310. [DOI] [PubMed] [Google Scholar]