MIMOSINE-INDUCED CELL-DEATH AND RELATED CHROMATIN CHANGES

The non-protein amino acid mimosine has recently been shown to induce an unusual mode of tell death that differs from necrosis and apoptosis , the two fundamental schemes of cell death. The drug affects primaril y the cell nucleus and induces first condensation of the chromatin int o a regular network of fibrils and then gradual decondensation. The pr esent study was performed to evaluate effective mimosine concentration s, time dependency of toxicity, and mimosine-related alterations of th e chromatin, DNA and histones. To this end, primarily cultured carp he patocytes were exposed to a wide range of mimosine (10(-1) to 10(-4) M ) up to 12 h and investigated by means of light microscopy, electron m icroscopy, and histochemistry for DNA and histones. With 10(-1) M mimo sine severe cytopathological transformations were obtained already aft er 3 h whereas 10(-2) M was cytotoxic only after 12 h. Lower concentra tions were ineffective within the experimental period. Cytopathology s tarted with condensation of the chromatin into a homogeneous network o f ca. 25 nm wide fibrils and segregation of the nucleolus. In parallel , the nuclei were depleted from histones leaving the pattern of DNA fl uorescence largely unchanged. The following period of chromatin decond ensation was characterized by removal of electron-dense components fro m the condensed chromatin fibrils and gradual loss of the DNA. The seg regated nucleolus and also the nuclear pores remained well preserved u ntil final cell lysis.