Effect of histone deacetylase inhibitors on the cell nucleus and nucleolus of leukemic myeloblasts in vitro - a cytochemical study.
The present study was designed to provide complementary information on the effects of histone deacetylase inhibitors (HDACi's) such as trichostatin A (TSA) and sodium valproate (VAP) on nuclei and nucleoli of leukemic myeloblasts represented by cultured Kasumi-1 cells. The number of apoptotic cells and bodies with characteristic chromatin condensation and fragmentation was greater after TSA treatment. However, in contrast to TSA, myeloblasts treated with VPA recovered and started to proliferate again. TSA-treated myeloblasts with a fine chromatin structure exhibited an intense phagocytosis of cell fragments. The decreased number and translocation of silver-stained proteins of nucleolus organiser regions (AgNORs) in large nucleoli of myeloblasts treated with HDACi's indicated that these cells entered apoptosis and/or ageing without preceding terminal maturation. The nucleolar asynchrony observed in an increased number of treated cells with both HDACi's studied here possibly represented myeloblasts resistant to such treatment. In conclusion, this study demonstrates that the chromatin structure and nucleoli visualised by simple cytochemical procedures provides useful information on the effects of HDACi's on myeloblasts and facilitated detection of these effects at the single cell level.
Smetana
K
K
Institute of Haematology and Blood Transfusion, Prague, Czech Republic. karel.smetana@uhkt.cz
Zápotocký
M
M
Starková
J
J
Trka
J
J
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects* / Q000201:enzymology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology*
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011480:Protease Inhibitors; C012589:trichostatin A; D014635:Valproic Acid; D006655:Histone Deacetylases