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J Cell Biol. 1963 May 1; 17(2): 299–313.
PMCID: PMC2106200



Disaggregated mouse embryo cells, grown in monolayers, underwent a progressive decline in growth rate upon successive transfer, the rapidity of the decline depending, among other things, on the inoculation density. Nevertheless, nearly all cultures developed into established lines within 3 months of culture. The first sign of the emergence of an established line was the ability of the cells to maintain a constant or rising potential growth rate. This occurred while the cultures were morphologically unchanged. The growth rate continued to increase until it equaled or exceeded that of the original culture. The early established cells showed an increasing metabolic autonomy, as indicated by decreasing dependence on cell-to-cell feeding. It is suggested that the process of establishment involves an alteration in cell permeability properties. Chromosome studies indicated that the cells responsible for the upturn in growth rate were diploid, but later the population shifted to the tetraploid range, often very rapidly. Still later, marker chromosomes appeared. Different lines acquired different properties, depending on the culture conditions employed; one line developed which is extremely sensitive to contact inhibition.

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Selected References

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  • HAFF RF, SWIM HE. Serial propagation of 3 strains of rabbit fibroblasts; their susceptibility to infection with vaccinia virus. Proc Soc Exp Biol Med. 1956 Nov;93(2):200–204. [PubMed]
  • EAGLE H, OYAMA VI, LEVY M, FREEMAN AE. Myo-Inositol as an essential growth factor for normal and malignant human cells in tissue culture. J Biol Chem. 1957 May;226(1):191–205. [PubMed]
  • DULBECCO R, VOGT M. Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med. 1954 Feb;99(2):167–182. [PMC free article] [PubMed]
  • HASTINGS J, FREEDMAN S, RENDON O, COOPER HL, HIRSCHHORN K. Culture of human white cells using differential leucocyte separation. Nature. 1961 Dec 23;192:1214–1215. [PubMed]
  • SANFORD KK, EARLE WR, LIKELY GD. The growth in vitro of single isolated tissue cells. J Natl Cancer Inst. 1948 Dec;9(3):229–246. [PubMed]
  • EARLE WR, SANFORD KK, EVANS VJ, WALTZ HK, SHANNON JE., Jr The influence of inoculum size on proliferation in tissue cultures. J Natl Cancer Inst. 1951 Aug;12(1):133–153. [PubMed]
  • Fisher HW, Puck TT. ON THE FUNCTIONS OF X-IRRADIATED "FEEDER" CELLS IN SUPPORTING GROWTH OF SINGLE MAMMALIAN CELLS. Proc Natl Acad Sci U S A. 1956 Dec;42(12):900–906. [PMC free article] [PubMed]
  • MOSER H. Modern approaches to the study of mammalian cells in culture. Experientia. 1960 Sep 15;16:385–398. [PubMed]
  • GREEN H, NILAUSEN K. Repression of growth of mammalian cells under agar. Nature. 1962 Apr 28;194:406–407. [PubMed]
  • ROTHFELS KH, PARKER RC. The karyotypes of cell lines recently established from normal mouse tissues. J Exp Zool. 1959 Oct-Dec;142:507–520. [PubMed]
  • FOLEY GE, DROLET BP, McCARTHY RE, GOULET KA, DOKOS JM, FILLER DA. Isolation and serial propagation of malignant and normal cells in semi-defined media. Origins of CCRF cell lines. Cancer Res. 1960 Jul;20:930–939. [PubMed]
  • PUCK TT, CIECIURA SJ, ROBINSON A. Genetics of somatic mammalian cells. III. Long-term cultivation of euploid cells from human and animal subjects. J Exp Med. 1958 Dec 1;108(6):945–956. [PMC free article] [PubMed]
  • HSU TC, BILLEN D, LEVAN A. Mammalian chromosomes in vitro. XV. Patterns of transformation. J Natl Cancer Inst. 1961 Sep;27:515–541. [PubMed]
  • YERGANIAN G, LEONARD MJ. Maintenance of normal in situ chromosomal features in long-term tissue cultures. Science. 1961 May 19;133(3464):1600–1601. [PubMed]
  • MACPHERSON I, STOKER M. Polyoma transformation of hamster cell clones--an investigation of genetic factors affecting cell competence. Virology. 1962 Feb;16:147–151. [PubMed]
  • RUDDLE FH. Chromosome variation in cell populations derived from pig kidney. Cancer Res. 1961 Aug;21:885–894. [PubMed]
  • EAGLE H, PIEZ K. The population-dependent requirement by cultured mammalian cells for metabolites which they can synthesize. J Exp Med. 1962 Jul 1;116:29–43. [PMC free article] [PubMed]
  • PUCK TT, MARCUS PI, CIECIURA SJ. Clonal growth of mammalian cells in vitro; growth characteristics of colonies from single HeLa cells with and without a feeder layer. J Exp Med. 1956 Feb 1;103(2):273–283. [PMC free article] [PubMed]
  • LEVINE S. Effect of manipulation on 32P loss from tissue culture cells. Exp Cell Res. 1960 Mar;19:220–227. [PubMed]

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