X-irradiation enhances the expression of Bcl-2 in HL-60 cells: The resulting effects on apoptosis and radiosensitivity

Although p53 has been shown to directly activate transcriptional bax gene a nd to inhibit expression of bcl-2 gene during radiation-induced apoptosis, it is poorly understood how the Bcl-2 family changes, in p53-deficient cell s: during radiation-induced apoptosis. The present work describes the effec t of X-irradiation on the apoptosis of p53-deficient HL-60 cells as assesse d by means of several methods. Apoptosis of HL-60 cells was induced by X-ir radiation in a dose- and time-dependent manner. 18 h after 5 Gy irradiation , G(2) cells underwent apoptosis, while 15 Gy X-irradiation induced the dea th of G(1)/S cells by 6 h. After X-irradiation, expression of Bcl-2 was ele vated, while Bar expression was unchanged. We have isolated a clonal HL-60 variant following twice 5 Gy irradiation of HL-XR3 cells. These cells highl y expressed Bcl-2 (about 2-fold), showed a reduced activation of caspase-3, and were not only more resistant to X-irradiation-induced apoptosis but al so more radioresistant. These results suggest that HL-60 cells may resist a poptosis and radiation by increasing Bcl-2 expression, and that this elevat ed Bcl-2 expression might be one of the causes of the phenomenon, often see n clinically, that tumor cells gradually acquire radioresistance during fra ctionated radiation therapy.