1,10-PHENANTHROLINE INHIBITION OF LYMPHOBLAST CELL-CYCLE

  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (7) , 2050-2056
Abstract
The effects of the metal chelating agent, 1,10-phenanthroline (OP), on cell cycle progression of CCRF-CEM [human leukemia] lymphoblasts was studied by flow microfluorometry. Lymphoblasts were incubated with 2,3-dihydro-1H-imidazo[1,2-b]pyrazole to block them in G1-early S. The block was reversed by incubating the cells in fresh media. Within 2-4 h .apprx. 90% of the cells were in S phase and, by 6 h .apprx. 80% were in late S. Aliquots of these latter cells were incubated with podophyllotoxin to block them in G2-M [mitosis]. These cells divided within 4 h of reversal of the podophyllotoxin block. Lymphoblast populations in G1-early S, mid-S or G2-M were incubated with 4 .mu.M 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 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.