Natural-killer (NK) cell-derived malignant tumors, such as angiocentric lymphoma, is often resistant to various chemotherapeutic agents and follows an aggressive clinical course. We report the effects of physiological oxidants (hydrogen peroxide, H2O2; sodium hypochlorite, NaOCl and monochloramine, NH2Cl) on the cell growth and cell death in a multidrug-resistant NK tumor cell line, NK-YS. Among the oxidants tested, NH2Cl was most cytotoxic, in which more than 90% of the cells died at 150 nmol/1 x 10(6) cells. H2O2 was less cytotoxic, whereas NaOCl showed no significant cell death at this dose. The cell death induced by NH2Cl was accompanied by DNA cleavage and caspase activation, which suggested apoptosis. In addition, lower dose of NH2Cl (70 nmol/1 x 10(6) cells) retarded cell growth and inhibited the cell cycle transition from G1 to S. This cell cycle arrest accompanied a decrease in the phosphorylation of retinoblastoma tumor suppressor protein at serine 795. These observations suggest that NH2Cl may induce apoptotic cell death and growth arrest in multidrug-resistant NK cell tumors.