Determination ot time- and dose-dependent features of apoptosis induced im human leukemia cells by antitumor drdqs

Antileukemic efficacy of chemotherapeutic compounds is thought to be mostly due to killing leukemia cells by apoptosis. .Thus, assessment of apoptosis in vitro nay provide a means to test for chemosensitivity of leukemia cells. However, time course of apoptosis varies greatly depending on many factors including cell cycle and metabolic status of cells, traits of antitumor agents and drug concentration. Thus, an accurate measurement of apoptosis requires either multiple end point determinations of biochemical or morphological hallmarks of apoptosis, or continuous monitoring of apoptosis. In the present study the time- and dose-dependent features of apoptotic responses of myelogenous leukemia HL-60 and erythroleukemia K-S62 cells to etoposide (1-ieomkM), doxorubicin (l-80rakM) and cisplatin (12.5-800mkM) were explored in a 6Oh Microculture Kinetic Assay (MiCK assay) which was developed by us to monitor apoptosis in non-disrupted cell cultures (1) . Both time course and extent of apoptotic responses varied prominently between HL-60 and K-562 cells with HL-60 cells to be more susceptible to apoptosis induced by low doses of all drugs. Results of the MiCK assay were validated by morphological and DNA fragmentation tests and related to Bcl-2 and p53 proteins levels in the cells. 1. Kravtsov VD, Fabian I. Lab Invest,1996,74,557-570.