Euchromatin megabase cleavages and conjoint apoptotic-autophagic death expression with nucleolar ball-and-socket joint dislocations in human Chang liver cells arrested in S-phase by etoposide

Etoposide induced a megabase (Mb) fragmentation pattern identical with that from genomic digestion by NotI restriction endonuclease which specifically cleaves CpG islands in euchromatin domains. Redigestion by NotI produced n o change, suggesting cleavage in the same or closely related sites in euchr omatin domains. Preferential euchromatin cleavage was further suggested by harvested metaphase chromosomes showing self-inflicted resolution of light G-bandings (R-bandings), the euchromatin domains. Autodegeneration followin g Mb euchromatin fragmentations was shown by their degradation into 200 bp ladders, and expressions of apoptotic and "non-apoptotic" active death morp hologies that were also seen conjointly in the same cell. The endstage furt her showed heterochromatin masses anchored to the nucleolus by novel ball-a nd-socket joints where dislocations occurred with nuclear leakage.