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.