Objective: To study the relationship on the dose effect and time effect of apoptosis induced by harringtonine (HT) and
benzoazene (BAZ) in tumor cells and the change of growth and decline between
apoptosis and necrosis. Methods:Ascitic cells of sarcoma 180 (S 180 ) of mice in vivo and human promyelocyte leukemia HL60 cells in vitro were used as models. The cells were stained with Hoechst 33342 and were observed under fluorescence microscope,the apoptosis index was counted. The ultra structure of the cells was examined with transmission electron microscope and DNA distribution was analyzed with FCM to define apoptosis. The statistical method of repeated measure analysis of variance was used to analyze the data. The trypan blue positive rate was used as a parameter of necrosis to investigate the possible relationship between apoptosis and necrosis. Results:Both of HT and BAZ could induce apoptosis of tumor cells. The typical apoptosis was confirmed by the examination of fluorescence microscope and transmission electron microscope. The sub G1 peak was found in DNA histogram by FCM. In HL60 cells ,during the 2～24 hrs,in the dose range of 0.02～1.0 μg/ml of HT,and of 0.2～5 μg/ml of BAZ,the apoptosis index was rising with the time passing and the concentration increasing. After 24 hrs,the apoptosis index reduced and the trypan blue positive rate rised. The highest concentration of drugs in this experiment (HT in 5.0 μg/ml,BAZ in 25 μg/ml) induced the lowest apoptosis index and the highest trypan blue positive rate (necrosis). In the mice bearing S 180 tumor,during 2～48hrs,and in the dose range of 25～250 mg/kg of BAZ,the apoptosis index was rising with the time passing and the dose increasing. Forty eight hours later,the apoptosis index decreased and the trypan blue positive rate increased. Conclusions:Antitumor drugs induce apoptosis of tumor cells,the relationship between dose effect and time effect was found in certain range of dose and time. High dose of drugs kills tumor cells by necrosis mainly. It implicated that the threshold value of intensity and time of damage may be important in the switching on and the regulating of apoptosis and necrosis.