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 no change, suggesting cleavage in the same or closely related sites in euchromatin 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 following Mb euchromatin fragmentations was shown by their degradation into 200 bp ladders, and expressions of apoptotic and "non-apoptotic" active death morphologies that were also seen conjointly in the same cell. The endstage further showed heterochromatin masses anchored to the nucleolus by novel ball-and-socket joints where dislocations occurred with nuclear leakage.