Alcaín F J, Löw H, Crane F L
Department of Cell Biology, University of Córdoba, Spain.
Biochem Mol Biol Int. 1997 Feb;41(2):303-10. doi: 10.1080/15216549700201311.
The synthesis of DNA in CCl 39 cells is inhibited by the presence of the Fe2+ chelator bathophenanthroline disulfonate (BPS) when growth is stimulated by thrombin EGF plus insulin, but not by fetal calf serum. The presence of transferrin and Fe3+ in fetal calf serum can be the basis for lack of BPS effect with serum. The impermeable Fe3+ chelator Tiron does not, by itself, inhibit growth factor induced DNA synthesis, but it induces together with BPS inhibition on fetal calf serum induced DNA synthesis. The combined effect of BPS and Tiron is similar to inhibition of DNA synthesis by impermeable polyvalent DTPA which can chelate both Fe2+ and Fe3+ but does not inhibit ribonucleotide reductase in intact cells. Ferrous iron that bind BPS can relieve the inhibition at stoichiometric concentration. Ferric iron also prevents the inhibition even though it does not bind BPS. BPS does not inhibit DNA synthesis in HeLa cells. BPS reacts with iron from CCl 39 cells but not from HeLa cells. Data show that iron available for impermeable external chelators is in the ferrous state, and that exogenous iron should be reduced before it reverses the inhibition.
当凝血酶、表皮生长因子（EGF）加胰岛素刺激CCl 39细胞生长时，Fe2+螯合剂4,7-二苯基-1,10-菲啰啉二磺酸（BPS）的存在会抑制其DNA合成，但胎牛血清不会产生这种抑制作用。胎牛血清中运铁蛋白和Fe3+的存在可能是血清不存在BPS效应的原因。不可渗透的Fe3+螯合剂钛铁试剂本身不会抑制生长因子诱导的DNA合成，但它与BPS共同作用时会抑制胎牛血清诱导的DNA合成。BPS和钛铁试剂的联合作用类似于不可渗透的多价二乙三胺五乙酸（DTPA）对DNA合成的抑制，DTPA可以螯合Fe2+和Fe3+，但不会抑制完整细胞中的核糖核苷酸还原酶。与BPS结合的亚铁离子在化学计量浓度下可以解除抑制作用。三价铁即使不与BPS结合也能阻止抑制作用。BPS不会抑制HeLa细胞中的DNA合成。BPS与CCl 39细胞中的铁发生反应，但不与HeLa细胞中的铁反应。数据表明，可用于不可渗透的外部螯合剂的铁处于亚铁状态，并且外源性铁在逆转抑制作用之前应该被还原。
