Falchuk K H, Krishan A
Cancer Res. 1977 Jul;37(7 Pt 1):2050-6.
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, approximately 90% of the cells were in S phase and, by 6 hr, approximately 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 micronM 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.
通过流式细胞荧光测定法研究了金属螯合剂1,10 - 菲咯啉（OP）对CCRF - CEM淋巴母细胞细胞周期进程的影响。将淋巴母细胞与2,3 - 二氢 - 1H - 咪唑并[1,2 - b]吡唑孵育，以便将它们阻滞在G1期早期S期。然后通过在新鲜培养基中孵育细胞来解除阻滞。在2至4小时内，约90%的细胞处于S期，到6小时时，约80%处于S期后期。然后将这些后期细胞的等分试样与鬼臼毒素孵育，以将它们阻滞在G2 - M期。这些细胞在鬼臼毒素阻滞解除后的4小时内分裂。然后将处于G1期早期S期、S期中期或G2 - M期的淋巴母细胞群体与4μM的OP孵育。OP阻滞G1期细胞进入S期以及通过S期的进程，但对从G2 - M期到G1期的进程没有影响。通过添加Zn2 +、Cu2 +或Fe2 +或通过在生长培养基中稀释螯合剂可逆转OP的作用。用OP的非螯合类似物1,7 - 菲咯啉孵育CCRF - CEM淋巴母细胞不会影响细胞周期。数据表明，OP通过螯合参与那些细胞周期事件所必需过程的金属，可逆地阻滞细胞从G1期到S期以及通过S期的进程。
