DETECTION OF HIGHER-ORDER 50-KBP AND 10-KBP DNA FRAGMENTS BEFORE APOPTOTIC INTERNUCLEOSOMAL CLEAVAGE AFTER TRANSIENT CEREBRAL-ISCHEMIA

DNA fragments of 50 and 10 kbp were found in ischemic brain in adult r ats following two-vessel occlusion or in neonates following hypoxia-is chemia. These higher-order fragments were detected before any laddered oligonucleosomal DNA fragmentation characteristic of apoptosis. Both the 50- and 10-kbp fragments were also detected during necrosis produc ed by decapitation, but these led to smeared smaller fragments, not la ddered patterns. End-group analysis showed the presence of both 3'-OH and 5'-OH ends in both the 50- and 10-kbp fragments but the predominan ce of 3'-OH ends in the laddered fragments. A higher proportion of 5'- OH to 3'-OH ends was found in the 10-kbp fragment compared to the larg er 50-kbp fragment, suggesting a selective degradation of the 50-kbp D NA fragment to the laddered oligonucleosomal patterns. Overall, the mo de of DNA fragmentation appeared different from that described in clas sic apoptosis of thymocytes.