Abstract
Growth rate of human leukaemic cell line K562 was independent of intracellular folate concentration when this was greater than 1.5 microM. When intracellular folate concentration was less than 1.5 microM, the rate of growth was proportional to the logarithm of intracellular concentration of non-methylated fully reduced folates, but not to the logarithm of the intracellular concentration of N5-methyltetrahydropteroylglutamate. Intracellular folate concentration sufficient to support an optimal growth rate was maintained by either DL-N5-formyltetrahydropteroylglutamate or DL-N5-methyltetrahydropteroylglutamate at a 100-fold lower concentration than pteroylglutamate. Addition of hypoxanthine to culture medium partially restored growth of folate-depleted cells: thymidine had no effect on growth rate either alone or in combination with thymidine. Folate-depleted cells with diminished growth rate were larger than replete cells, but did not have megaloblastic morphology. The mitotic index was not decreased in cultures with diminished growth rate. The rate of growth and cell size of K562 cells is thus dependent on a critical intracellular concentration of non-methylated tetrahydrofolates, which may be maintained by different concentrations of either reduced folates or pteroylglutamate.
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Selected References
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- Andersson L. C., Nilsson K., Gahmberg C. G. K562--a human erythroleukemic cell line. Int J Cancer. 1979 Feb;23(2):143–147. doi: 10.1002/ijc.2910230202. [DOI] [PubMed] [Google Scholar]
- Buehring K. U., Tamura T., Stokstad E. L. Folate coenzymes of Lactobacillus casei and Streptococcus faecalis. J Biol Chem. 1974 Feb 25;249(4):1081–1089. [PubMed] [Google Scholar]
- COLEMAN D. H., DONOHUE D. M., FINCH C. A., MOTULSKY A. G., REIFF R. H. Erythrokinetics in pernicious anemia. Blood. 1956 Sep;11(9):807–820. [PubMed] [Google Scholar]
- Cooper B. A. Superiority of simplified assay for folate with Lactobacillus casei ATCC 7469 over assay with chloramphenicol-adapted strain. J Clin Pathol. 1973 Dec;26(12):963–967. doi: 10.1136/jcp.26.12.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halpern B. C., Clark B. R., Hardy D. N., Halpern R. M., Smith R. A. The effect of replacement of methionine by homocystine on survival of malignant and normal adult mammalian cells in culture. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1133–1136. doi: 10.1073/pnas.71.4.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hilton J. G., Cooper B. A., Rosenblatt D. S. Folate polyglutamate synthesis and turnover in cultured human fibroblasts. J Biol Chem. 1979 Sep 10;254(17):8398–8403. [PubMed] [Google Scholar]
- Hoffman R. M., Erbe R. W. High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine. Proc Natl Acad Sci U S A. 1976 May;73(5):1523–1527. doi: 10.1073/pnas.73.5.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
- Marie J. P., Izaguirre C. A., Civin C. I., Mirro J., McCulloch E. A. The presence within single K-562 cells of erythropoietic and granulopoietic differentiation markers. Blood. 1981 Oct;58(4):708–711. [PubMed] [Google Scholar]
- McBurney M. W., Whitmore G. F. Isolation and biochemical characterization of folate deficient mutants of Chinese hamster cells. Cell. 1974 Jul;2(3):173–182. doi: 10.1016/0092-8674(74)90091-9. [DOI] [PubMed] [Google Scholar]
- Mellman I., Willard H. F., Youngdahl-Turner P., Rosenberg L. E. Cobalamin coenzyme synthesis in normal and mutant human fibroblasts. Evidence for a processing enzyme activity deficient in cblC cells. J Biol Chem. 1979 Dec 10;254(23):11847–11853. [PubMed] [Google Scholar]
- Rondanelli E. G., Magliulo E., Verona-Rinati M., Petrocini S. Chronologie du cycle mitotique des cellules érythropoiétiques humaines normales. Etude par la microcinématographie en contraste de phase sur des cellules en culture "in vitro". Nouv Rev Fr Hematol. 1969 May-Jun;9(3):347–364. [PubMed] [Google Scholar]
- Rosenblatt D. S., Cooper B. A., Lue-Shing S., Wong P. W., Berlow S., Narisawa K., Baumgartner R. Folate distribution in cultured human cells. Studies on 5,10-CH2-H4PteGlu reductase deficiency. J Clin Invest. 1979 May;63(5):1019–1025. doi: 10.1172/JCI109370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rutherford T. R., Clegg J. B., Weatherall D. J. K562 human leukaemic cells synthesise embryonic haemoglobin in response to haemin. Nature. 1979 Jul 12;280(5718):164–165. doi: 10.1038/280164a0. [DOI] [PubMed] [Google Scholar]
- Wickramasinghe S. N., Chalmers D. G., Cooper E. H. Arrest of cell proliferation and protein synthesis in megaloblasts of pernicious anaemia. Acta Haematol. 1969;41(2):65–75. doi: 10.1159/000208834. [DOI] [PubMed] [Google Scholar]
