Radiosensitization effect of zidovudine on human malignant glioma cells

• Published in: Biochemical and biophysical research communications Vol. 354; no. 2; pp. 351 - 356
• Main Authors: Zhou, Fu-Xiang, Liao, Zheng-Kai, Dai, Jing, Xiong, Jie, Xie, Cong-Hua, Luo, Zhi-Guo, Liu, Shi-Quan, Zhou, Yun-Feng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.03.2007
• Subjects: AZT; BIOLOGICAL REPAIR; CELL DIVISION; Cell Line, Tumor; DNA; GAMMA RADIATION; Glioma - drug therapy; Glioma - pathology; Glioma - radiotherapy; GLIOMAS; Humans; IRRADIATION; RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; Radiation-Sensitizing Agents - therapeutic use; RADIOSENSITIVITY; RADIOTHERAPY; Reverse transcriptase inhibitors; Reverse Transcriptase Inhibitors - therapeutic use; SOMATIC CELLS; STRAND BREAKS; Telomerase; Telomerase - antagonists & inhibitors; Telomerase - metabolism; Telomere; TELOMERES; TUMOR CELLS; Zidovudine - therapeutic use; DSBs; SER; Radiosensitivity; SSBs; TM; TRF; Reverse transcriptase inhibitors; AZT; TA; Telomere; Telomerase
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.12.180

Telomeres are shortened with each cell division and play an important role in maintaining chromosomal integrity and function. Telomerase, responsible for telomere synthesis, is activated in 90% of human tumor cells but seldom in normal somatic cells. Zidovudine (AZT) is a reverse transcriptase inhibitor. In this study, we have investigated the effects of γ-radiation in combination with AZT on telomerase activity (TA), telomere length, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and the changes in radiosensitivity of human malignant glioma cell line U251. The results showed that the TA was suppressed by AZT but enhanced by irradiation, resulting in a deceleration of restored rate of shortened telomere, decreased repair rate of DNA strand breaks, and increased radiosensitivity of U251 cells. Our results suggested that telomerase activity and telomere length may serve as markers for estimating the efficacy of cancer radiotherapy and reverse transcriptase inhibitors, such as AZT, may be used clinically as a new radiosensitizer in cancer radiotherapy.