This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Falchuk, K. H. Articles by Sullivan, J. Search for Related Content PubMed PubMed Citation Articles by Falchuk, K. H. Articles by Sullivan, J.

1,10-Phenanthroline Inhibition of Lymphoblast Cell Cycle¹

Biophysics Research Laboratory, Department of Biological Chemistry, Medicine [K. H. F.], and Pathology [A. K.], Harvard Medical School, Peter Bent Brigham Hospital 02115 and the Laboratories of Cytokinetics, Sidney Farber Cancer Institute, Boston, Massachusetts 02115

The effects of the metal-chelating agent, 1,10-phenanthroline (OP), on the cell cycle progression of CCRF-CEM lymphoblasts has been studied by flow microfluorometry. Lymphoblasts were incubated with 2,3-dihydro-1H-imidazo[1,2-b]pyrazole in order to block them in G₁-early S. The block was then reversed by incubating the cells in fresh media. Within 2 to 4 hr, 90% of the cells were in S phase and, by 6 hr, 80% were in late S. Aliquots of these latter cells then were incubated with podophyllotoxin to block them in G₂-M. These cells divided within 4 hr of reversal of the podophyllotoxin block. Lymphoblast populations in G₁-early S, mid-S, or G₂-M were then incubated with 4 µM OP. OP blocked entry of G₁ cells into S as well as progression through S but had no effect on progression from G₂-M to G₁. The OP effects were reversed by addition of Zn²⁺, Cu²⁺, or Fe²⁺ or by dilution of the chelating agent in the growth media. Incubation of CCRF-CEM lymphoblasts with 1,7-phenanthroline, a nonchelating analog of OP, did not affect the cell cycle. The data indicate that OP reversibly blocks progression of cells from G₁ to S and through S by chelation of metals involved in processes essential for those cell cycle events.

¹ This work is supported by Grant-in-Aid GM-15003 from the NIH, Department of Health, Education and Welfare and CA-06516 and 1 RO1 CA 20008-01 from the National Cancer Institute.

² Investigator of the Howard Hughes Medical Institute. To whom requests for reprints should be addressed.

Received 11/11/76. Accepted 4/ 5/77.