Involvement of Fenton reaction products in differentiation induction of K562 human leukemia cells.

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.