CHANGES OF MITOCHONDRIAL MASS IN THE HEMATOPOIETIC STEM-CELL LINE FDCP-MIX AFTER TREATMENT WITH ETOPOSIDE - A CORRELATIVE STUDY BY MULTIPARAMETER FLOW-CYTOMETRY AND CONFOCAL AND ELECTRON-MICROSCOPY

FDCP-Mix, a pluripotent murine hemopoietic stem cell line which underg oes typical internucleosomal cleavage of DNA when induced to apoptosis by either drugs or withdrawal of growth factor (interleukin-3) was st udied after treatment with the topoisomerase II inhibitor etoposide (0 .5-4 mu M). An increase in autolytic activity was the major early morp hological change within the cytoplasm, with mitochondria as the main t arget for autolytic digestion. Despite this macroautophagy, thin secti ons showed a high number of mitochondria, suggesting mitochondrial pro liferation as a result of drug treatment. This observation of an incre ase in the number of mitochondria was confirmed by flow cytometric stu dies of mitochondrial overall mass. Multiparameter flow cytometry of c ells double stained with propidium iodide and nonyl-acridine orange ga ve an accurate assay for mitochondrial mass in relation to cell cycle stages. The increase in mitochondrial mass was found in all cell cycle stages. The results suggest a drug-induced proliferation of mitochond ria separate from the processes involved in the doubling of mitochondr ial mass during the cell cycle and a decline of mitochondria in the la ter stages of apoptosis. (C) 1995 Academic Press, Inc.