TY - JOUR
T1 - 1,10 Phenanthroline inhibition of lymphoblast cell cycle
AU - Falchuk, K. H.
AU - Krishan, A.
PY - 1977/12/1
Y1 - 1977/12/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 861934
AN - SCOPUS:0017710288
VL - 37
SP - I
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 7
ER -