Dual mode cytotoxicities of reactive oxygens on L5178Y radiosensitive mutant M10

Cytotoxic effects of O2- and H2O2 on mammalian cells were investigated in comparison with the relative sensitivity of mouse L5178Y cells and its radiosensitive mutant M10. Both O2- and H2O2 exhibited two different modes of cytotoxic actions depending on their exposure rates: At a high exposure rate (4.3 nmol of O2-/mL/min), M10 was more sensitive to O2- than L5178Y normal type cell, in agreement with the case of X-rays; while at a low exposure rate (five times less than the high exposure rate), M10 became more resistant than L5178Y. Similar results were obtained with H2O2. Reactive species responsible for these two different cytotoxic actions were examined with special reference to the metal-catalyzed Haber-Weiss reaction, by using a metal chelator, 1,10-phenanthroline, and an .OH scavenger, dimethylsulfoxide (DMSO). Significant protection by 1,10-phenanthroline was observed, which indicates the presence of a metal-dependent process in both cytotoxic actions. DMSO showed a marked protective effect, except for the case of M10 exposed at the low exposure rate, in which DMSO showed no protection. The resistance of M10 to O2- and H2O2 observed at the low exposure rate suggests the possibility that reactive species other than .OH are involved in the cytotoxicity.