High-throughput screening identifies two classes of antibiotics as radioprotectors: tetracyclines and fluoroquinolones.
High-throughput screening identifies two classes of antibiotics as radioprotectors: tetracyclines and fluoroquinolones.
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DOI：
10.1158/1078-0432.ccr-09-1964
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发表时间：
2009-12-01
期刊：
影响因子：
--
通讯作者：
McBride WH
中科院分区：
文献类型：
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作者：
Kim K;Pollard JM;Norris AJ;McDonald JT;Sun Y;Micewicz E;Pettijohn K;Damoiseaux R;Iwamoto KS;Sayre JW;Price BD;Gatti RA;McBride WH
Discovery of agents that protect or mitigate normal tissue from radiation injury during radiotherapy, accidents, or terrorist attacks, is of importance. Specifically, bone marrow insufficiency, with possible infection due to immune suppression, can occur after total body irradiation (TBI) or regional irradiation and is a major component of the acute radiation syndrome. The purpose of this study was to identify novel radioprotectors and mitigators of the hematopoietic system. High throughput screening of small molecule libraries was performed using viability of a murine lymphocyte line as a read out with further validation in human lymphoblastoid cells. The selected compounds were then tested for their ability to counter TBI lethality in mice. All of two major classes of antibiotics, tetracyclines and fluoroquinolones, which share a common planar ring moiety, were radioprotective. Furthermore, tetracycline protected murine hematopoietic stem/progenitor cell populations from radiation damage and allowed 87.5% of mice to survive when given before and 35% when given 24 h after lethal TBI. Interestingly, tetracycline did not alter the radiosensitivity of Lewis lung cancer cells. Tetracycline and ciprofloxacine also protected human lymphoblastoid cells, reducing radiation-induced DNA double strand breaks by 33% and 21%, respectively. The effects of these agents on radiation lethality are not due to the classical mechanism of free radical scavenging but potentially through activation of the histone acetyl transferase Tip60 and altered chromatin structure. Tetracyclines and fluoroquinolones can be robust radioprotectors and mitigators of the hematopoietic system with potential utility in anti-cancer radiotherapy and radiation emergencies.
