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. 1979 Nov;40(5):755–760. doi: 10.1038/bjc.1979.257

Cell-cycle inhibition by misonidazole of human cells cultivated in vitro under aerobic conditions.

T Lindmo, E O Pettersen, E Wibe
PMCID: PMC2010116  PMID: 508579

Abstract

By means of flow cytometric recording of DNA histograms and counting of cells in synchronized populations, we have found that misonidazole (MIS) in clinically relevant concentrations induces cell-kinetic changes in human cells (NHIK 3025) cultivated in vitro under aerobic conditions. The effect seems to be a general lengthening of the cell cycle, affecting all phases. However, induction of this effect is phase-dependent, since only cells exposed to MIS during mitosis and/or early G1 will suffer significant cell-cycle prolongation. In exponentially growing populations this effect of MIS leads to a transient increase in the fraction of G1 cells and a corresponding decrease in the fraction of S cells. The possible significance of this effect for the clinical use of MIS is discussed.

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Selected References

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

  1. Brown J. M. Selective radiosensitization of the hypoxic cells of mouse tumors with the nitroimidazoles metronidazole and Ro 7-0582. Radiat Res. 1975 Dec;64(3):633–647. [PubMed] [Google Scholar]
  2. Crissman H. A., Tobey R. A. Cell-cycle analysis in 20 minutes. Science. 1974 Jun 21;184(4143):1297–1298. doi: 10.1126/science.184.4143.1297. [DOI] [PubMed] [Google Scholar]
  3. Dische S., Saunders M. I., Flockhart I. R. The optimum regime for the administration of misonidazole and the establishment of multi-centre clinical trials. Br J Cancer Suppl. 1978 Jun;3:318–321. [PMC free article] [PubMed] [Google Scholar]
  4. Dische S., Saunders M. I., Lee M. E., Adams G. E., Flockhart I. R. Clinical testing of the radiosensitizer Ro 07-0582: experience with multiple doses. Br J Cancer. 1977 May;35(5):567–579. doi: 10.1038/bjc.1977.90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Geard C. R., Povlas S. F., Astor M. B., Hall E. J. Cytological effects of 1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol (misonidazole) on hypoxic mammalian cells in vitro. Cancer Res. 1978 Mar;38(3):644–649. [PubMed] [Google Scholar]
  6. Hall E. J., Roizin-Towle L. Hypoxic sensitizers: radiobiological studies at the cellular level. Radiology. 1975 Nov;117(2):453–457. doi: 10.1148/117.2.453. [DOI] [PubMed] [Google Scholar]
  7. Kogelnik H. D., Meyer J. H., Jentzsch K., Szepesi T., Kärcher K. H., Maida E., Mamoli B., Wessely P., Zaunbauer F. Further clinical experiences of a phase I study with the hypoxic cell radiosensitizer misonidazole. Br J Cancer Suppl. 1978 Jun;3:281–285. [PMC free article] [PubMed] [Google Scholar]
  8. Lindmo T., Pettersen E. O. Delay of cell cycle progression after X-irradiation of synchronized populations of human cells (NHIK 3025) in culture. Cell Tissue Kinet. 1979 Jan;12(1):43–57. doi: 10.1111/j.1365-2184.1979.tb00112.x. [DOI] [PubMed] [Google Scholar]
  9. Lindmo T., Steen H. B. Flow cytometric measurement of the polarization of fluorescence from intracellular fluorescein in mammalian cells. Biophys J. 1977 May;18(2):173–187. doi: 10.1016/S0006-3495(77)85606-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Miller R. C., Hall E. J. Oncogenic transformation in vitro by the hypoxic cell sensitizer misonidazole. Br J Cancer. 1978 Sep;38(3):411–417. doi: 10.1038/bjc.1978.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Moore B. A., Palcic B., Skarsgard L. D. Radiosensitizing and toxic effects on the 2-nitroimidazole Ro-07-0582 in hypoxic mammation cells. Radiat Res. 1976 Sep;67(3):459–473. [PubMed] [Google Scholar]
  12. PUCK T. T., CIECIURA S. J., FISHER H. W. Clonal growth in vitro of human cells with fibroblastic morphology; comparison of growth and genetic characteristics of single epithelioid and fibroblast-like cells from a variety of human organs. J Exp Med. 1957 Jul 1;106(1):145–158. doi: 10.1084/jem.106.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pettersen E. O., Bakke O., Lindmo T., Oftebro R. Cell cycle characteristics of synchronized and asynchronous populations of human cells and effect of cooling of selected mitotic cells. Cell Tissue Kinet. 1977 Nov;10(6):511–522. doi: 10.1111/j.1365-2184.1977.tb00309.x. [DOI] [PubMed] [Google Scholar]
  14. Sinclair W. K. Cyclic x-ray responses in mammalian cells in vitro. Radiat Res. 1968 Mar;33(3):620–643. [PubMed] [Google Scholar]
  15. Stratford I. J., Adams G. E. Effect of hyperthermia on differential cytotoxicity of a hypoxic cell radiosensitizer, Ro-07-0582, on mammalian cells in vitro. Br J Cancer. 1977 Mar;35(3):307–313. doi: 10.1038/bjc.1977.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Stratford I. J. Split dose cytotoxic experiments with misonidazole. Br J Cancer. 1978 Jul;38(1):130–136. doi: 10.1038/bjc.1978.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Taylor Y. C., Rauth A. M. Differences in the toxicity and metabolism of the 2-nitroimidazole misonidazole (Ro-07-0582) in HeLa and Chinese hamster ovary cells. Cancer Res. 1978 Sep;38(9):2745–2752. [PubMed] [Google Scholar]
  18. Thomlinson R. H., Dische S., Gray A. J., Errington L. M. Clinical testing of the radiosensitiser Ro-07-0582. III. Response of tumours. Clin Radiol. 1976 Apr;27(2):167–174. doi: 10.1016/s0009-9260(76)80139-0. [DOI] [PubMed] [Google Scholar]

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