Ultrastructural study of apoptotic U937 [corrected] cells treated with different pro-apoptotic substances

Human monocytic leukemia U937 cells readily undergo apoptosis when exposed to various stimuli, including inhibition of protein synthesis, oxidative stress, antitumoral agents, etc. The sequential, step-by-step morphological changes in U937 cells that occur during the apoptotic program are largely determined by the activation of a specific class of proteases, the caspases. The action of these proteases were followed at the ultrastructural level. From our observations 1) no unique morphological feature exists during apoptosis, even in the same cell type; 2) the extent of the morphological modifications are inducer- and dose-dependent; 3) double or triple treatments amplify the morphological modifications with a single inducer, but not the rate of apoptosis; and 4) in the case of double treatment the second inducer has to have a cytoplasmatic target because damage to the cytoplasm occurs before nuclear modifications become visible. These data should facilitate a more objective evaluation of apoptosis in conditions where antiproliferative drugs, like antiblastic or immunosuppressive molecules, are used to monitor the efficiency of treatment.