Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1974 Dec 1;63(3):773–779. doi: 10.1083/jcb.63.3.773

SOME BIOCHEMICAL PROPERTIES OF CHINESE HAMSTER CELLS SENSITIVE AND RESISTANT TO ACTINOMYCIN D

Robert H F Peterson 1, Judith A O'Neil 1, June L Biedler 1
PMCID: PMC2109379  PMID: 4474176

Abstract

A graded series of drug-resistant Chinese hamster sublines has been examined for biochemical changes accompanying resistance to actinomycin D. The most highly resistant subline, DC-3F/AD X, is maintained at 10 µg/ml of the antibiotic. It was shown that over 250 times more actinomycin D is required to inhibit RNA synthesis in this subline than in the parental DC-3F line. The DC-3F/AD X subline was also shown to have a somewhat reduced capacity to transport uridine as compared to parental cells. Sensitive cells took up over 50 times more tritiated antibiotic than the most resistant cells, as determined in a 1-h assay. Uptake of actinomycin D was shown to be temperature-dependent in both resistant and sensitive cells and was not influenced by various metabolic inhibitors. Resistance could not be explained by a rapid uptake and release of the antibiotic, as demonstrated in efflux experiments, or by its metabolism. In addition, highly resistant cells which are cross-resistant to puromycin were shown to have a reduced capacity to take up labeled puromycin. These studies provide further evidence indicating that the mechanism of resistance to actinomycin D is reduced permeability to drug and suggesting that cell membrane alteration accounts for resistance to both actinomycin D and puromycin.

Full Text

The Full Text of this article is available as a PDF (604.1 KB).

Selected References

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

  1. Biedler J. L., Riehm H. Cellular resistance to actinomycin D in Chinese hamster cells in vitro: cross-resistance, radioautographic, and cytogenetic studies. Cancer Res. 1970 Apr;30(4):1174–1184. [PubMed] [Google Scholar]
  2. Bosmann H. B. Mechanism of cellular drug resistance. Nature. 1971 Oct 22;233(5321):566–569. doi: 10.1038/233566a0. [DOI] [PubMed] [Google Scholar]
  3. Ennis H. L., Möller L., Wang J. J., Selawry O. S. 2,3-Dihydro-1H-imidazo(1,2-b)pyrazole: a new inhibitor of deoxyribonucleic acid synthesis. Biochem Pharmacol. 1971 Oct;20(10):2639–2646. doi: 10.1016/0006-2952(71)90173-0. [DOI] [PubMed] [Google Scholar]
  4. GOLDBERG I. H., RABINOWITZ M., REICH E. Basis of actinomycin action. I. DNA binding and inhibition of RNA-polymerase synthetic reactions by actinomycin. Proc Natl Acad Sci U S A. 1962 Dec 15;48:2094–2101. doi: 10.1073/pnas.48.12.2094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Kessel D., Bosmann H. B. On the characteristics of actinomycin D resistance in L5178Y cells. Cancer Res. 1970 Nov;30(11):2695–2701. [PubMed] [Google Scholar]
  7. Kessel D., Wodinsky I. Uptake in vivo and in vitro of actinomycin D by mouse leukemias as factors in survival. Biochem Pharmacol. 1968 Jan;17(1):161–164. doi: 10.1016/0006-2952(68)90170-6. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Nigam V. N., Lallier R., Brailovsky C. Ganglioside patterns and phenotypic characteristics in a normal variant and a transformed back variant of a simian virus 40-induced hamster tumor cell line. J Cell Biol. 1973 Aug;58(2):307–316. doi: 10.1083/jcb.58.2.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Rhode S. L., 3rd, Ellem K. A. Control of nucleic acid synthesis in human diploid cells undergoing contact inhibition. Exp Cell Res. 1968 Oct;53(1):184–204. doi: 10.1016/0014-4827(68)90366-2. [DOI] [PubMed] [Google Scholar]
  11. Riehm H., Biedler J. L. Cellular resistance to daunomycin in Chinese hamster cells in vitro. Cancer Res. 1971 Apr;31(4):409–412. [PubMed] [Google Scholar]
  12. Riehm H., Biedler J. L. Potentiation of drug effect by Tween 80 in Chinese hamster cells resistant to actinomycin D and daunomycin. Cancer Res. 1972 Jun;32(6):1195–1200. [PubMed] [Google Scholar]
  13. Sawicki S. G., Godman G. C. On the recovery of transcription after inhibition by actinomycin D. J Cell Biol. 1972 Nov;55(2):299–309. doi: 10.1083/jcb.55.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Simard R., Cassingena R. Actinomycin resistance in cultured hamster cells. Cancer Res. 1969 Aug;29(8):1590–1597. [PubMed] [Google Scholar]
  15. Wicker BOURALI M. F., Suarez H. G., Cassingena R. Propriétés d'une lignée de cellules de hamster transformées par le virus SV40 et résistantes a l'actinomycine. Int J Cancer. 1972 Nov;10(3):632–640. doi: 10.1002/ijc.2910100323. [DOI] [PubMed] [Google Scholar]

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

RESOURCES