Dexrazoxane activates DDR. Phosphorylations of Chk1 at Ser317 (pChk1) and Chk2 at Thr68 (pChk2) (A), and of ATR at Ser428 (pATR) and ATM at Ser1981 (pATM) (B) were detected by Western blot. Total Chk1, Chk2, ATM or ATR was used as loading controls. TOP2A-expressing HTETOP cells were exposed to 100 μM dexrazoxane (DRZ) for the indicated time periods. (C) HTETOP cells were exposed to ATR inhibitor VE-821 (10 μM for 30 min), followed by 24 h treatment with 100 μM dexrazoxane. pChk1 (Ser317) and total Chk1 protein levels were detected by Western blot. (D) Total p53 protein level determined by Western blot in TOP2A-expressing HTETOP cells incubated with 100 μM dexrazoxane for the indicated time periods. Quantitative data are mean values from three experiments. (E) Caspase 3/7 activity in TOP2A-expressing HTETOP cells following 100 μM dexrazoxane for the indicated time periods. n = 5. *P < 0.05, **P < 0.01, significantly different as indicated. All Western blots represent at least three independent experiments. RLU, relative light units.