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. 1982 Apr;79(8):2569–2573. doi: 10.1073/pnas.79.8.2569

Serum enhances the cycling and survival of HeLa cells treated with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole.

I Tamm, T Kikuchi, J S Murphy
PMCID: PMC346241  PMID: 6953414

Abstract

We have defined the growth kinetics of HeLa cell populations by determining the frequencies of mitoses and deaths and the lengths of intermitotic intervals. This was done by time-lapse cinemicrography. Untreated control cells proliferated at closely similar rates in medium enriched with 5% or 15% fetal calf serum, with an average of 4% dividing and less than 0.1% dying per hr. The mean intermitotic interval was 16 hr during exponential growth of the control populations. In contrast, in cultures treated with 40 or 60 microM 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a selective inhibitor of heterogeneous nuclear RNA synthesis, the frequency of mitoses was markedly and directly dependent on serum concentration, whereas the frequency of deaths was inversely dependent. DRB prolonged the intermitotic interval in cells cycling in the presence of the drug, but the effect was less in 15% than in 5% serum. After prolonged treatment of HeLa cells with DRB, the inhibition of heterogeneous nuclear RNA synthesis by DRB appeared to be reduced, which was not due to inactivation of DRB in the culture medium.

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Selected References

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

  1. BABLANIAN R., EGGERS H. J., TAMM I. STUDIES ON THE MECHANISM OF POLIOVIRUS-INDUCED CELL DAMAGE. I. THE RELATION BETWEEN POLIOVIRUS,-INDUCED METABOLIC AND MORPHOLOGICAL ALTERATIONS IN CULTURED CELLS. Virology. 1965 May;26:100–113. doi: 10.1016/0042-6822(65)90030-9. [DOI] [PubMed] [Google Scholar]
  2. Chadwick D. E., Ignotz G. G., Ignotz R. A., Lieberman I. Inhibitors of RNA synthesis and passage of chick embryo fibroblasts through the G1 period. J Cell Physiol. 1980 Jul;104(1):61–72. doi: 10.1002/jcp.1041040110. [DOI] [PubMed] [Google Scholar]
  3. DAWSON K. B., MADOC-JONES H., FIELD E. O. VARIATIONS IN THE GENERATION TIMES OF A STRAIN OF RAT SARCOMA CELLS IN CULTURE. Exp Cell Res. 1965 Apr;38:75–84. doi: 10.1016/0014-4827(65)90429-5. [DOI] [PubMed] [Google Scholar]
  4. Madoc-Jones H., Bruce W. R. On the mechanism of the lethal action of 5-fluorouracil on mouse L cells. Cancer Res. 1968 Oct;28(10):1976–1981. [PubMed] [Google Scholar]
  5. Sehgal P. B., Darnell J. E., Jr, Tamm I. The inhibition by DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) of hnRNA and mRNA production in HeLa cells. Cell. 1976 Nov;9(3):473–480. doi: 10.1016/0092-8674(76)90092-1. [DOI] [PubMed] [Google Scholar]
  6. Sehgal P. B., Gupta S. L. Regulation of the stability of poly(I)xpoly(C)-induced human fibroblast interferon mRNA: selective inactivation of interferon mRNA and lack of involvement of 2',5'-oligo(A) synthetase activation during the shutoff of interferon production. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3489–3493. doi: 10.1073/pnas.77.6.3489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Sehgal P. B., Lyles D. S., Tamm I. Superinduction of human fibroblast interferon production: further evidence for increased stability of interferon mRNA. Virology. 1978 Aug;89(1):186–198. doi: 10.1016/0042-6822(78)90051-x. [DOI] [PubMed] [Google Scholar]
  8. Sehgal P. B., Tamm I. Halogenated benzimidazole ribosides, Novel inhibitors of RNA synthesis. Biochem Pharmacol. 1978;27(21):2475–2485. doi: 10.1016/0006-2952(78)90313-1. [DOI] [PubMed] [Google Scholar]
  9. Sehgal P. B., Tamm I., Vilcek J. Human interferon production: superinduction by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole. Science. 1975 Oct 17;190(4211):282–284. doi: 10.1126/science.1179208. [DOI] [PubMed] [Google Scholar]
  10. Skehan P., Friedman S. J. Cellular senescence and the analysis of generation time distributions. Cell Biol Int Rep. 1979 Sep;3(6):535–542. doi: 10.1016/0309-1651(79)90089-4. [DOI] [PubMed] [Google Scholar]
  11. TAMM I., FOLKERS K., SHUNK C. H., HORSFALL F. L., Jr Inhibition of influenza virus multiplication by N-glycosides of benzimidazoles-N. J Exp Med. 1954 Mar;99(3):227–250. doi: 10.1084/jem.99.3.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Tamm I. Definition of subclasses of nucleoplasmic RNA. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5011–5015. doi: 10.1073/pnas.74.11.5011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Tamm I., Hand R., Caliguiri L. A. Action of dichlorobenzimidazole riboside on RNA synthesis in L-929 and HeLa cells. J Cell Biol. 1976 May;69(2):229–240. doi: 10.1083/jcb.69.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Tamm I., Kikuchi T., Darnell J. E., Jr, Salditt-Georgieff M. Short capped hnRNA precursor chains in HeLa cells: continued synthesis in the presence of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole. Biochemistry. 1980 Jun 10;19(12):2743–2748. doi: 10.1021/bi00553a032. [DOI] [PubMed] [Google Scholar]
  15. Tamm I., Kikuchi T. Early termination of heterogeneous nuclear RNA transcripts in mammalian cells: accentuation by 5,6-dichloro 1-beta-D-ribofuranosylbenzimidazole. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5750–5754. doi: 10.1073/pnas.76.11.5750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tamm I., Pfeffer L. M., Murphy J. S. Assay of the inhibitory activities of human interferons on the proliferation and locomotion of fibroblasts. Methods Enzymol. 1981;79(Pt B):404–413. doi: 10.1016/s0076-6879(81)79052-9. [DOI] [PubMed] [Google Scholar]
  17. Tamm I., Sehgal P. B. A comparative study of the effects of certain halogenated benzimidazole ribosides on RNA synthesis, cell proliferation, and interferon production. J Exp Med. 1977 Feb 1;145(2):344–356. doi: 10.1084/jem.145.2.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Weizsaecker M., Deen D. F. Effect of feeder cell-released substances on the survival of clonogenic 9L cells after treatment with antimetabolites. Cancer Res. 1980 Sep;40(9):3202–3205. [PubMed] [Google Scholar]
  19. Wheeler K. T., Tel N., Williams M. E., Sheppard S., Levin V. A., Kabra P. M. Factors influencing the survival of rat brain tumor cells after in vitro treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea. Cancer Res. 1975 Jun;35(6):1464–1469. [PubMed] [Google Scholar]

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