Abstract
We have previously shown that Chinese hamster ovary cells made polyamine deficient by treatment with alpha-methylornithine, an inhibitor of ornithine decarboxylase, grow exponentially in culture at low densities at one-half the rate observed in untreated (control) cultures. In this study, the cell cycle of polyamine-limited cells was examined by using thymidine autoradiography, mitotic index analysis, and fraction labeled mitoses analysis. We found that the longer doubling time of inhibitor-treated cultures was a consequence of increases in the lengths of the G1 and S phases. The expansion of the S phase was proportional to the increase in doubling time (twofold), whereas the G1 phase was lengthened by slightly more than a factor of 2. The lengths of the G2 and M phases were essentially unchanged. Putrescine stimulated the growth of inhibitor-treated cultures and restored the cell cycle parameters to those of untreated cells.
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Selected References
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- Abdel-Monem M. M., Newton N. E., Weeks C. E. Inhibitors of polyamine biosynthesis. 1. Alpha-methyl-(plus or minus)-ornithine, an inhibitor of ornithine decarboxylase. J Med Chem. 1974 Apr;17(4):447–451. doi: 10.1021/jm00250a016. [DOI] [PubMed] [Google Scholar]
- Corti A., Dave C., Williams-Ashman H. G., Mihich E., Schenone A. Specific inhibition of the enzymic decarboxylation of S-adenosylmethionine by methylglyoxal bis(guanylhydrazone) and related substances. Biochem J. 1974 May;139(2):351–357. doi: 10.1042/bj1390351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fillingame R. H., Jorstad C. M., Morris D. R. Increased cellular levels of spermidine or spermine are required for optimal DNA synthesis in lymphocytes activated by concanavalin A. Proc Natl Acad Sci U S A. 1975 Oct;72(10):4042–4045. doi: 10.1073/pnas.72.10.4042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HAM R. G. An improved nutrient solution for diploid Chinese hamster and human cell lines. Exp Cell Res. 1963 Feb;29:515–526. doi: 10.1016/s0014-4827(63)80014-2. [DOI] [PubMed] [Google Scholar]
- Heby O., Andersson G., Gray J. W. Interference with S and G2 phase progression by polyamine synthesis inhibitors. Exp Cell Res. 1978 Feb;111(2):461–464. doi: 10.1016/0014-4827(78)90192-1. [DOI] [PubMed] [Google Scholar]
- Liskay R. M. Absence of a measurable G2 phase in two Chinese hamster cell lines. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1622–1625. doi: 10.1073/pnas.74.4.1622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mamont P. S., Böhlen P., McCann P. P., Bey P., Schuber F., Tardif C. Alpha-methyl ornithine, a potent competitive inhibitor of ornithine decarboxylase, blocks proliferation of rat hepatoma cells in culture. Proc Natl Acad Sci U S A. 1976 May;73(5):1626–1630. doi: 10.1073/pnas.73.5.1626. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Otani S., Mizoguchi Y., Matsui I., Morisawa S. Inhibition of DNA synthesis by methylglyoxal bis(guanylhydrazone) during lymphocyte transformation. Mol Biol Rep. 1974 Dec;1(8):431–436. doi: 10.1007/BF00360667. [DOI] [PubMed] [Google Scholar]
- PUCK T. T., CIECIURA S. J., ROBINSON A. Genetics of somatic mammalian cells. III. Long-term cultivation of euploid cells from human and animal subjects. J Exp Med. 1958 Dec 1;108(6):945–956. doi: 10.1084/jem.108.6.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
- PUCK T. T., STEFFEN J. LIFE CYCLE ANALYSIS OF MAMMALIAN CELLS. I. A METHOD FOR LOCALIZING METABOLIC EVENTS WITHIN THE LIFE CYCLE, AND ITS APPLICATION TO THE ACTION OF COLCEMIDE AND SUBLETHAL DOSES OF X-IRRADIATION. Biophys J. 1963 Sep;3:379–397. doi: 10.1016/s0006-3495(63)86828-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pardee A. B., Dubrow R., Hamlin J. L., Kletzien R. F. Animal cell cycle. Annu Rev Biochem. 1978;47:715–750. doi: 10.1146/annurev.bi.47.070178.003435. [DOI] [PubMed] [Google Scholar]
- Pöso H., Jänne J. Inhibition of ornithine decarboxylase activity and spermidine accumulation in regenerating rat liver. Biochem Biophys Res Commun. 1976 Apr 19;69(4):885–892. doi: 10.1016/0006-291x(76)90456-3. [DOI] [PubMed] [Google Scholar]
- QUASTLER H., SHERMAN F. G. Cell population kinetics in the intestinal epithelium of the mouse. Exp Cell Res. 1959 Jun;17(3):420–438. doi: 10.1016/0014-4827(59)90063-1. [DOI] [PubMed] [Google Scholar]
- Rao P. N., Sunkara P. S. Correlation between the high rate of protein synthesis during mitosis and the absence of G1 period in V79-8 cells. Exp Cell Res. 1980 Feb;125(2):507–511. doi: 10.1016/0014-4827(80)90148-2. [DOI] [PubMed] [Google Scholar]
- Rivin C. J., Fangman W. L. Cell cycle phase expansion in nitrogen-limited cultures of Saccharomyces cerevisiae. J Cell Biol. 1980 Apr;85(1):96–107. doi: 10.1083/jcb.85.1.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Rupniak H. T., Paul D. Inhibition of spermidine and spermine synthesis leads to growth arrest of rat embryo fibroblasts in G1. J Cell Physiol. 1978 Feb;94(2):161–170. doi: 10.1002/jcp.1040940205. [DOI] [PubMed] [Google Scholar]
- Seyfried C. E., Morris D. R. Relationship between inhibition of polyamine biosynthesis and DNA replication in activated lymphocytes. Cancer Res. 1979 Dec;39(12):4861–4867. [PubMed] [Google Scholar]
- Sunkara P. S., Pargac M. B., Nishioka K., Rao P. N. Differential effects of inhibition of polyamine biosynthesis on cell cycle traverse and structure of the prematurely condensed chromosomes of normal and transformed cells. J Cell Physiol. 1979 Mar;98(3):451–457. doi: 10.1002/jcp.1040980303. [DOI] [PubMed] [Google Scholar]
- Sunkara P. S., Rao P. N., Nishioka K. Putrescine biosynthesis in mammalial cells: essential for DNA synthesis but not for mitosis. Biochem Biophys Res Commun. 1977 Feb 7;74(3):1125–1153. doi: 10.1016/0006-291x(77)91635-7. [DOI] [PubMed] [Google Scholar]
- TERASIMA T., TOLMACH L. J. Growth and nucleic acid synthesis in synchronously dividing populations of HeLa cells. Exp Cell Res. 1963 Apr;30:344–362. doi: 10.1016/0014-4827(63)90306-9. [DOI] [PubMed] [Google Scholar]
- Tobey R. A., Anderson E. C., Petersen D. F. The effect of thymidine on the duration of G1 in Chinese hamster cells. J Cell Biol. 1967 Oct;35(1):53–59. doi: 10.1083/jcb.35.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]