INVOLVEMENT OF FENTON REACTION-PRODUCTS IN DIFFERENTIATION INDUCTION OF K562 HUMAN LEUKEMIA-CELLS

INVOLVEMENT OF FENTON REACTION-PRODUCTS IN DIFFERENTIATION INDUCTION OF K562 HUMAN LEUKEMIA-CELLS
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DOI:
10.1016/0145-2126(94)00138-z
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发表时间:
1995-03-01
期刊:
影响因子:
2.7
通讯作者:
IMRE, ZN
IMRE, ZN
中科院分区:
医学3区
文献类型:
--
作者:
NAGY, K;PASTI, G;IMRE, ZN

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将芬顿反应的组分ADP-Fe 2+(或ATP-Fe 2+)络合物和H2 O2加入K562细胞中,然后培养96 h。Ara-C诱导的分化作为比较的基础。细胞数量,活力,联苯胺染色,胸苷掺入,并通过流式细胞术细胞周期分布进行了测定。芬顿试剂以剂量依赖性方式降低白血病细胞的生长速率和胸苷掺入,就加入的H2 O2而言(从0.01到1.0 mM),伴随着血红蛋白在其中的积累。细胞的分化伴随着相当大的变化,总SOD和过氧化氢酶活性。Ara-C使SOD活性增加366%,过氧化氢酶活性增加235%,而完全芬顿反应使SOD活性增加705%,过氧化氢酶活性降低38%。酶诱导的这些变化表明分化细胞中存在较高的H2 O2通量。实验结果与芬顿反应产物中OH.通过异源裂解从H2 O2衍生的自由基可能在细胞分化中起因果作用,而这些自由基的过度产生导致细胞的老化或死亡。
ADP-Fe2+ (or ATP-Fe2+) complex and H2O2, components of the Fenton reaction, were added to K562 cells, then cultured for 96 h. Ara-C-induced differentiation served as a basis for comparison. Cell numbers, viability, benzidine staining, thymidine incorporation, and cell-cycle distribution by means of flow cytometry were determined. The Fenton reagents reduced the growth rate and thymidine incorporation of leukemic cells in a dose-dependent manner as regards the added H2O2 (from 0.01 to 1.0 mM), accompanied by an accumulation of hemoglobin in them. Differentiation of the cells was accompanied by considerable changes in total SOD and catalase activities. Ara-C caused an increase of SOD to 366%, and of catalase to 235%, while the complete Fenton reaction resulted in SOD increase to 705% and catalase decrease to 38% of the untreated control cultures. These shifts in enzyme inductions suggest the existence of a higher H2O2 flux in the differentiating cells. The results are consistent with the assumption that products of the Fenton reaction, among them OH. radicals deriving from H2O2 by heterolysis, may play a causal role in cell differentiation, whereas an overproduction of these radicals causes aging or death of the cells.