Dual mode cytotoxicities of reactive oxygens on L5178Y radiosensitive mutant M10

Abstract Cytotoxic effects of O 2 − and H 2 O 2 on mammalian cells were investigated in comparison with the relative sensitivity of mouse L5178Y cells and its radiosensitive mutant M10. Both O 2 − and H 2 O 2 exhibited two different modes of cytotoxic actions depending on their exposure rates: At a high exposure rate (4.3 nmol of O 2 − /mL/min), M10 was more sensitive to O 2 − 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 H 2 O 2 . 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 O 2 − and H 2 O 2 observed at the low exposure rate suggests the possibility that reactive species other than . OH are involved in the cytotoxicity.