Stimulation of endogenous endonuclease activity in hepatocytes exposed to oxidative stress.

Incubation of freshly isolated rat hepatocytes with moderately toxic concentrations of menadione [2-methyl-1,4-naphthoquinone) resulted in chromatin condensation and progressive DNA fragmentation, suggestive of the stimulation of an endogenous endonuclease activity previously found to be involved in programmed cell death (apoptosis). Endonuclease activation followed upon a sustained increase in cytosolic Ca2+ concentration and preceded cell killing by 1-2 h. It is concluded that generation of oxidative stress in hepatocytes can activate processes similar to those observed during programmed cell death.