ROLE OF PEROXIDE AND SUPEROXIDE ANION DURING TUMOR-CELL APOPTOSIS

Apoptosis or programmed cell death was induced in the human promyelocy tic leukemia cell line HL-60 by UV irradiation or treatment with cytot oxic drugs (etoposide, camptothecin, melphalan or chlorambucil). These treatments caused a rapid increase in intracellular peroxide levels. Preincubation of HL-60 cells with the hydrogen peroxide-scavenging enz yme catalase (500 U/ml) inhibited apoptosis due to UV irradiation or l ow concentrations of camptothecin, etoposide or melphalan, but did not protect against higher concentrations. In contrast, superoxide anion levels in the cells remained unchanged upon treatment with cytotoxic d rugs, while UV irradiation led to a transient doubling in superoxide l evels. Exogenous superoxide dismutase (400 U/ml) provided modest prote ction against UV irradiation and had no effect on cytotoxic drug-induc ed apoptosis. The results suggest that both hydrogen peroxide and supe roxide anion may be involved in the induction of apoptosis by UV irrad iation. On the other hand, while exposure to cytotoxic drugs induces a large increase in intracellular peroxide levels, catalase is able to protect the cells from apoptosis only when low concentrations of these compounds are used, thus indicating the involvement of other factors in this process, particularly at higher drug concentrations. (C) 1997 Federation of European Biochemical Societies.