Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1969 Aug 1;42(2):366–376. doi: 10.1083/jcb.42.2.366

CELL KILLING BY ACTINOMYCIN D IN RELATION TO THE GROWTH CYCLE OF CHINESE HAMSTER CELLS

M M Elkind 1, E Kano 1, H Sutton-Gilbert 1
PMCID: PMC2107666  PMID: 5792326

Abstract

Using Chinese hamster cells in culture, we have measured the effectiveness of actinomycin D to suppress division as a function of the position, or age, of a cell in its growth cycle. Cells were first exposed to millimolar concentrations of hydroxyurea in order to produce a synchronized population just before the onset of DNA synthesis. Thereafter, the survival response after 30 min exposures to actinomycin D was measured. Cells become resistant as they enter the S phase and then sensitive again in the latter part of S. When they reach G2 (or G2-mitosis) they are maximally resistant; at 1.0 µg/ml, for example, the survival in G2 is 30-fold greater than it is in G1. These results, plus measurements reported earlier on the interaction of damage in S cells due to actinomycin D and X-irradiation, suggest that the age-response pattern of the toxic effects of this drug probably reflects both the functional capacity of DNA-actinomycin complexes and the ability of this antibiotic to penetrate chromatin and bind to DNA.

Full Text

The Full Text of this article is available as a PDF (678.2 KB).

Selected References

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

  1. Camargo E. P., Plaut W. The radioautographic detection of DNA with tritiated actinomycin D. J Cell Biol. 1967 Dec;35(3):713–716. doi: 10.1083/jcb.35.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. EAGLE H. Nutrition needs of mammalian cells in tissue culture. Science. 1955 Sep 16;122(3168):501–514. doi: 10.1126/science.122.3168.501. [DOI] [PubMed] [Google Scholar]
  3. ELKIND M. M., SUTTON H., MOSES W. B. Postirradiation survival kinetics of mammalian cells grown in culture. J Cell Comp Physiol. 1961 Dec;58(3):113–134. doi: 10.1002/jcp.1030580412. [DOI] [PubMed] [Google Scholar]
  4. ELKIND M. M., SUTTON H. Radiation response of mammalian cells grown in culture. 1. Repair of X-ray damage in surviving Chinese hamster cells. Radiat Res. 1960 Oct;13:556–593. [PubMed] [Google Scholar]
  5. Elkind M. M., Sutton-Gilbert H., Moses W. B., Kamper C. Sub-lethal and lethal radiation damage. Nature. 1967 Jun 10;214(5093):1088–1092. doi: 10.1038/2141088a0. [DOI] [PubMed] [Google Scholar]
  6. FORD D. K., YERGANIAN G. Observations on the chromosomes of Chinese hamster cells in tissue culture. J Natl Cancer Inst. 1958 Aug;21(2):393–425. [PubMed] [Google Scholar]
  7. Goldstein M. N., Hamm K., Amrod E. Incorporation of triated actinomycin D into drug-sensitive and drug-resistant HeLa cells. Science. 1966 Mar 25;151(3717):1555–1556. doi: 10.1126/science.151.3717.1555. [DOI] [PubMed] [Google Scholar]
  8. Müller W., Crothers D. M. Studies of the binding of actinomycin and related compounds to DNA. J Mol Biol. 1968 Jul 28;35(2):251–290. doi: 10.1016/s0022-2836(68)80024-5. [DOI] [PubMed] [Google Scholar]
  9. Pastan I., Friedman R. M. Actinomycin D: inhibition of phospholipid synthesis in chick embryo cells. Science. 1968 Apr 19;160(3825):316–317. doi: 10.1126/science.160.3825.316. [DOI] [PubMed] [Google Scholar]
  10. REICH E. ACTINOMYCIN: CORRELATION OF STRUCTURE AND FUNCTION OF ITS COMPLEXES WITH PURINES AND DNA. Science. 1964 Feb 14;143(3607):684–689. doi: 10.1126/science.143.3607.684. [DOI] [PubMed] [Google Scholar]
  11. Robbins E., Scharff M. D. The absence of a detectable G1 phase in a cultured strain of Chinese hamster lung cell. J Cell Biol. 1967 Aug;34(2):684–686. doi: 10.1083/jcb.34.2.684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. SINCLAIR W. K., MORTON R. A. X-RAY AND ULTRAVIOLET SENSITIVITY OF SYNCHRONIZED CHINESE HAMSTER CELLS AT VARIOUS STAGES OF THE CELL CYCLE. Biophys J. 1965 Jan;5:1–25. doi: 10.1016/s0006-3495(65)86700-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sinclair W. K. Hydroxyurea: differential lethal effects on cultured mammalian cells during the cell cycle. Science. 1965 Dec 24;150(3704):1729–1731. doi: 10.1126/science.150.3704.1729. [DOI] [PubMed] [Google Scholar]
  14. Sinclair W. K. Hydroxyurea: effects on Chinese hamster cells grown in culture. Cancer Res. 1967 Feb;27(2):297–308. [PubMed] [Google Scholar]
  15. Waring M. J. Drugs which affect the structure and function of DNA. Nature. 1968 Sep 28;219(5161):1320–1325. doi: 10.1038/2191320a0. [DOI] [PubMed] [Google Scholar]
  16. YOUNG C. W., HODAS S. HYDROXYUREA: INHIBITORY EFFECT ON DNA METABOLISM. Science. 1964 Nov 27;146(3648):1172–1174. doi: 10.1126/science.146.3648.1172. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES