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. 1990 Jan;61(1):14–21. doi: 10.1038/bjc.1990.5

Changes in growth characteristics and macromolecular synthesis on recovery from severe hypoxia.

R E Wilson 1, P C Keng 1, R M Sutherland 1
PMCID: PMC1971325  PMID: 1688709

Abstract

Chinese hamster ovary cells subjected to severe hypoxia stop growing. When oxygen was reintroduced growth resumed, but at a slower rate. The longer the hypoxic stress, the slower the recovery growth rate. Six hours of hypoxia caused very little decrease in growth rate while a 24 h period almost halved the rate. Short hypoxic periods resulted in almost no growth lag, while longer periods caused significant lag. Clonogenic survival was 60% after 12 h of hypoxia and rose slowly during recovery, reaching control levels after 60 h. Following 24 h of hypoxia, survival remained around 60% throughout recovery. The cell cycle distribution after hypoxia was similar to that of aerobic cultures. After 4-6 h of recovery, a subpopulation of cells entered S phase, and reached G2 by 12 h. During this time few G2-M cells divided. With longer recovery, cells much larger than aerobic cells emerged, containing greater than 4C DNA content and enhanced amounts of RNA. When these cells were isolated, they exhibited slightly slower growth kinetics, greatly lengthened lag time and decreased survival when compared to aerobic cells or the smaller cells. Most of the extra DNA and RNA was lost within one cell cycle.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Born R., Eichholtz-Wirth H. Effect of different physiological conditions on the action of adriamycin on Chinese hamster cells in vitro. Br J Cancer. 1981 Aug;44(2):241–246. doi: 10.1038/bjc.1981.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dean P. N., Jett J. H. Mathematical analysis of DNA distributions derived from flow microfluorometry. J Cell Biol. 1974 Feb;60(2):523–527. doi: 10.1083/jcb.60.2.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Heacock C. S., Sutherland R. M. Induction characteristics of oxygen regulated proteins. Int J Radiat Oncol Biol Phys. 1986 Aug;12(8):1287–1290. doi: 10.1016/0360-3016(86)90155-0. [DOI] [PubMed] [Google Scholar]
  4. Keng P. C., Li C. K., Wheeler K. T. Synchronization of 9L rat brain tumor cells by centrifugal elutriation. Cell Biophys. 1980 Sep;2(3):191–206. doi: 10.1007/BF02790449. [DOI] [PubMed] [Google Scholar]
  5. Koch C. J., Kruuv J., Frey H. E. Variation in radiation response of mammalian cells as a function of oxygen tension. Radiat Res. 1973 Jan;53(1):33–42. [PubMed] [Google Scholar]
  6. Luk C. K., Keng P. C., Sutherland R. M. Regrowth and radiation sensitivity of quiescent cells isolated from EMT6/Ro-fed plateau monolayers. Cancer Res. 1985 Mar;45(3):1020–1025. [PubMed] [Google Scholar]
  7. Martin W. M., McNally N. J. Cytotoxicity of adriamycin to tumour cells in vivo and in vitro. Br J Cancer. 1980 Dec;42(6):881–889. doi: 10.1038/bjc.1980.336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. POWERS W. E., TOLMACH L. J. A multicomponent x-ray survival curve for mouse lymphosarcoma cells irradiated in vivo. Nature. 1963 Feb 16;197:710–711. doi: 10.1038/197710b0. [DOI] [PubMed] [Google Scholar]
  9. Palcic B., Jaggi B. The use of solid-state image sensor technology to detect and characterize live mammalian cells growing in tissue culture. Int J Radiat Biol Relat Stud Phys Chem Med. 1986 Aug;50(2):345–352. doi: 10.1080/09553008614550721. [DOI] [PubMed] [Google Scholar]
  10. Rice G. C., Hoy C., Schimke R. T. Transient hypoxia enhances the frequency of dihydrofolate reductase gene amplification in Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5978–5982. doi: 10.1073/pnas.83.16.5978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rice G. C., Spiro I. J., Ling C. C. Detection of S-phase overreplication following chronic hypoxia using a monoclonal anti-BrdUrd. Int J Radiat Oncol Biol Phys. 1985 Oct;11(10):1817–1822. doi: 10.1016/0360-3016(85)90038-0. [DOI] [PubMed] [Google Scholar]
  12. Schimke R. T., Hill A., Johnston R. N. Fifth Gordon Hamilton-Fairley memorial lecture. Methotrexate resistance and gene amplification: an experimental model for the generation of cellular heterogeneity. Br J Cancer. 1985 Apr;51(4):459–465. doi: 10.1038/bjc.1985.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Schimke R. T. Methotrexate resistance and gene amplification. Mechanisms and implications. Cancer. 1986 May 15;57(10):1912–1917. doi: 10.1002/1097-0142(19860515)57:10<1912::aid-cncr2820571004>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  14. Shrieve D. C., Deen D. F., Harris J. W. Effects of extreme hypoxia on the growth and viability of EMT6/SF mouse tumor cells in vitro. Cancer Res. 1983 Aug;43(8):3521–3527. [PubMed] [Google Scholar]
  15. Smith E., Stratford I. J., Adams G. E. Cytotoxicity of adriamycin on aerobic and hypoxic chinese hamster V79 cells in vitro. Br J Cancer. 1980 Oct;42(4):568–573. doi: 10.1038/bjc.1980.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sutherland R. M., Keng P., Conroy P. J., McDermott D., Bareham B. J., Passalacqua W. In vitro hypoxic cytotoxicity of nitroimidazoles: uptake and cell cycle phase specificity. Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):745–748. doi: 10.1016/0360-3016(82)90726-x. [DOI] [PubMed] [Google Scholar]
  17. Sutherland R., Freyer J., Mueller-Klieser W., Wilson R., Heacock C., Sciandra J., Sordat B. Cellular growth and metabolic adaptations to nutrient stress environments in tumor microregions. Int J Radiat Oncol Biol Phys. 1986 Apr;12(4):611–615. doi: 10.1016/0360-3016(86)90070-2. [DOI] [PubMed] [Google Scholar]
  18. Tannock I. F. Oxygen diffusion and the distribution of cellular radiosensitivity in tumours. Br J Radiol. 1972 Jul;45(535):515–524. doi: 10.1259/0007-1285-45-535-515. [DOI] [PubMed] [Google Scholar]
  19. Van Putten L. M., Kallman R. F. Oxygenation status of a transplantable tumor during fractionated radiation therapy. J Natl Cancer Inst. 1968 Mar;40(3):441–451. [PubMed] [Google Scholar]
  20. Wilson R. E., Keng P. C., Sutherland R. M. Drug resistance in Chinese hamster ovary cells during recovery from severe hypoxia. J Natl Cancer Inst. 1989 Aug 16;81(16):1235–1240. doi: 10.1093/jnci/81.16.1235. [DOI] [PubMed] [Google Scholar]
  21. Wilson R. E., Sutherland R. M. Enhanced synthesis of specific proteins, RNA, and DNA caused by hypoxia and reoxygenation. Int J Radiat Oncol Biol Phys. 1989 Apr;16(4):957–961. doi: 10.1016/0360-3016(89)90895-x. [DOI] [PubMed] [Google Scholar]
  22. Young S. D., Marshall R. S., Hill R. P. Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9533–9537. doi: 10.1073/pnas.85.24.9533. [DOI] [PMC free article] [PubMed] [Google Scholar]

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