Giant DNA fragments (1-2 Mbp) were found in C6 rat glioma cells irradiated by a lethal dose of ultraviolet-C (UV-C, 254 nm) at 50 J/m(2). After irradiation, the fragments mutated into high-molecular-weight (100-800 kbp) DNA fragments and then into ladder-formed internucleosomal DNA fragments. Poly-ADP-ribose polymerase (PARP) activity and NAD levels were reduced during DNA fragmentation. Some inhibitors of caspase and protease inhibited DNA ladder formation, but not giant DNA fragmentation, whereas antioxidants did not inhibit DNA fragmentation. These results suggest that a lethal dose of UV radiation induces giant DNA fragmentation and leads to internucleosomal DNA fragmentation associated with apoptosis through some caspases and nonreactive oxygen species in cells.