Radiosensitization effect of zidovudine on human malignant glioma cells.
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 gamma-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.
Zhou
Fu-Xiang
FX
Department of Chemo-Radiotherapy Oncology, Zhongnan Hospital, Wuhan University, The Cancer Center of Wuhan University, Wuhan, Hubei 430071, China.
Liao
Zheng-Kai
ZK
Dai
Jing
J
Xiong
Jie
J
Xie
Cong-Hua
CH
Luo
Zhi-Guo
ZG
Liu
Shi-Quan
SQ
Zhou
Yun-Feng
YF
D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015215:Zidovudine / Q000627:therapeutic use*
D011838:Radiation-Sensitizing Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019098:Telomerase