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

• Published in: International journal of molecular medicine Vol. 3; no. 2; p. 145
• Main Authors: Kariya, S, Ogawa, Y, Yoshida, S, Yabuki, M, Imajo, Y, Utsumi, K
• Format: Journal Article
• Language: English
• Published: Greece 01.02.1999
• Subjects: Apoptosis - radiation effects; bcl-2-Associated X Protein; Cell Cycle - radiation effects; Cell Survival - radiation effects; DNA Fragmentation - drug effects; Dose-Response Relationship, Radiation; G1 Phase - radiation effects; Gene Expression; HL-60 Cells; Humans; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - physiology; Radiation Tolerance; S Phase - radiation effects; Time Factors
• ISSN: 1107-3756
• DOI: 10.3892/ijmm.3.2.145

Although p53 has been shown to directly activate transcriptional bax gene and to inhibit expression of bcl-2 gene during radiation-induced apoptosis, it is poorly understood how the Bcl-2 family changes in p53-deficient cells during radiation-induced apoptosis. The present work describes the effect of X-irradiation on the apoptosis of p53-deficient HL-60 cells as assessed by means of several methods. Apoptosis of HL-60 cells was induced by X-irradiation in a dose- and time-dependent manner. 18 h after 5 Gy irradiation, G2 cells underwent apoptosis, while 15 Gy X-irradiation induced the death of G1/S cells by 6 h. After X-irradiation, expression of Bcl-2 was elevated, while Bax expression was unchanged. We have isolated a clonal HL-60 variant following twice 5 Gy irradiation of HL-XR3 cells. These cells highly 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 also more radioresistant. These results suggest that HL-60 cells may resist apoptosis and radiation by increasing Bcl-2 expression, and that this elevated Bcl-2 expression might be one of the causes of the phenomenon, often seen clinically, that tumor cells gradually acquire radioresistance during fractionated radiation therapy.