Abstract
Inactivation of NHIK 3025 cells ny the mitotic inhibitor NY 3170 (1-propargyl-5-chloropyrimidin-2-one) was measured as loss of colony-forming ability. NY 3170 at a concentration of 0.15 nM allowed no formation of colonies after 12 days of continuous exposure to the drug. Metaphase arrest after treatment with NY 3170 was reversible if the drug was removed immediately after the onset of the arrest. When the cells were kept in mitosis by the presence of NY 3170, inactivation was complete after 8h incubation of mitotic cells with 0.4 nM NY 3170. Using synchronized cell populations, it was shown that mitosis is by far the most sensitive stage of the cell cycle to inactivation by NY 3170. This leads to the suggestion that there is a connection between the inactivating and the metaphase-arresting effect of this drug. The age response curves show that after mitosis the stages in order of decreasing sensitivity to NY3170 are: G2, late S, early S and G1. This is a similar age response to that reported for proliferating cells treated with bleomycin, whereas the mitotic inhibitors vincristine and vinblastine have shown qhite different age response curves.
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Selected References
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- Barranco S. C., Humphrey R. M. The effects of bleomycin on survival and cell progression in Chinese hamster cells in vitro. Cancer Res. 1971 Sep;31(9):1218–1223. [PubMed] [Google Scholar]
- Bruchovsky N., Owen A. A., Becker A. J., Till J. E. Effects of vinblastine on the proliferative capacity of L cells and their progress through the division cycle. Cancer Res. 1965 Sep;25(8):1232–1237. [PubMed] [Google Scholar]
- Dahl W. N., Oftebro R., Pettersen E. O., Brustad T. Inhibitory and cytotoxic effects of Oncovin (Vincristine sulfate) on cells of human line NHIK 3025. Cancer Res. 1976 Sep;36(9 PT1):3101–3105. [PubMed] [Google Scholar]
- Gacek M., Undheim K., Oftebro R., Laland S. G. Metahalones, a new class of metaphase inhibitors. FEBS Lett. 1979 Feb 15;98(2):355–358. doi: 10.1016/0014-5793(79)80216-1. [DOI] [PubMed] [Google Scholar]
- George P., Journey L. J., Goldstein M. N. Effect of vincristine on the fine structure of HeLa cells during mitosis. J Natl Cancer Inst. 1965 Aug;35(2):355–375. [PubMed] [Google Scholar]
- Gillespie C. J., Chapman J. D., Reuvers A. P., Dugle D. L. The inactivation of Chinese hamster cells by x rays: synchronized and exponential cell populations. Radiat Res. 1975 Nov;64(2):353–364. [PubMed] [Google Scholar]
- Krishan A. Time-lapse and ultrastructure studies on the reversal of mitotic arrest induced by vinblastine sulfate in Earle's L cells. J Natl Cancer Inst. 1968 Aug;41(2):581–595. [PubMed] [Google Scholar]
- Madoc-Jones H., Mauro F. Interphase action of vinblastine and vincristine: differences in their lethal action through the mitotic cycle of cultured mammalian cells. J Cell Physiol. 1968 Dec;72(3):185–196. doi: 10.1002/jcp.1040720306. [DOI] [PubMed] [Google Scholar]
- Mauro F., Madoc-Jones H. Age responses of cultured mammalian cells to cytotoxic drugs. Cancer Res. 1970 May;30(5):1397–1408. [PubMed] [Google Scholar]
- 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]
- Tucker R. W., Owellen R. J., Harris S. B. Correlation of cytotoxicity and mitotic spindle dissolution by vinblastine in mammalian cells. Cancer Res. 1977 Dec;37(12):4346–4351. [PubMed] [Google Scholar]
- Wibe E., Oftebro R., Laland S. G., Pettersen E. O., Lindmo T. Cell-cycle inhibitory effects of the mitotic inhibitor NY 3170 on human cells in vitro. Br J Cancer. 1979 Apr;39(4):391–397. doi: 10.1038/bjc.1979.71. [DOI] [PMC free article] [PubMed] [Google Scholar]