ZINC INHIBITS UV RADIATION-INDUCED APOPTOSIS BUT FAILS TO PREVENT SUBSEQUENT CELL-DEATH

Zinc ions inhibit the morphological and DNA fragmentation features of apoptosis in a number of systems. HL-60 cells pretreated with zinc and exposed to UV irradiation maintained their normal morphology for up t o 8 h, whereas non-zinc-treated cells underwent extensive apoptosis. Z inc pretreatment also inhibited both single and double-stranded DNA fr agmentation, which is characteristic of apoptosis. The most effective zinc concentration that blocked apoptosis over short incubation period s (up to 8 h) was also the most toxic over extended time periods (grea ter than or equal to 12 h). The mechanism of cell death at these longe r time periods was akin to necrosis, but occurred in the absence of an y DNA fragmentation. The effects of the nuclease inhibitor aurintricar boxylic acid (ATA) was also examined on UV-induced apoptosis in HL-60 cells. ATA had no toxic effects over the concentration range tested, b ut also failed to prevent DNA fragmentation in whole cells. Further an alysis showed that it effectively inhibited DNA fragmentation in isola ted nuclei.