Apoptotic agents inducing genotoxicity-specific chromatin changes.

To visualize characteristic chromatin distortions we have distinguished first among regularly occurring intermediates of chromatin structures in mammalian (Indian muntjac, CHO, murine preB, rat liver, rat myeloid leukemia, K562 human erythroid leukemia) and Drosophila nuclei. Fluorescence microscopy of chromatin structures isolated from nuclei of reversibly permeable cells revealed a common pathway of chromatin condensation in mammalian cells. Different intermediates in mammalian and Drosophila cells indicate alternative mechanisms of chromosome condensation. Genotoxic agents such as irradiation (alpha, gamma, UV-B) and heavy metals (Cd, Pb, Ni, Hg, Ag) caused alterations in chromatin structures leading to apoptosis. Injury-specific chromatin changes manifested at significantly lower concentrations than non-specific signs of cellular toxicity, suggesting that preapoptotic events are useful indicators of genotoxicity.