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 reac tion, were added to K562 cells, then cultured for 96 h. Ara-C-induced differentiation served as a basis for comparison. Cell numbers, viabil ity, benzidine staining, thymidine incorporation, and cell-cycle distr ibution by means of flow cytometry were determined. The Fenton reagent s reduced the growth rate and thymidine incorporation of leukemic cell s 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. Differen tiation 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 i n SOD increase to 705% and catalase decrease to 38% of the untreated c ontrol cultures. These shifts in enzyme inductions suggest the existen ce 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 thes e radicals causes aging or death of the cells.