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 to 8 h, whereas non-zinc-treated cells underwent extensive apoptosis. Zinc pretreatment also inhibited both single and double-stranded DNA fragmentation, which is characteristic of apoptosis. The most effective zinc concentration that blocked apoptosis over short incubation periods (up to 8 h) was also the most toxic over extended time periods (> or = 12 h). The mechanism of cell death at these longer time periods was akin to necrosis, but occurred in the absence of any DNA fragmentation. The effects of the nuclease inhibitor aurintricarboxylic acid (ATA) was also examined on UV-induced apoptosis in HL-60 cells. ATA had no toxic effects over the concentration range tested, but also failed to prevent DNA fragmentation in whole cells. Further analysis showed that it effectively inhibited DNA fragmentation in isolated nuclei.