Abstract #2298: High throughput screening identifies two classes of antibiotics: tetracycline and fluoroquinolone eliciting radioprotection

Whole body irradiation causes severe apoptotic cell death of radiation sensitive tissues. Among them, acute hematopoietic syndromes are serious problem even at low dose exposure. Thus, agents protecting immune system from radiation cytotoxicity would be immediately useful for the case of radiation emergencies. From a high throughput screening of over 33,000 compounds of small molecule libraries, two classes of antibiotics, tetracycline analogs and fluoroquinolones, clearly emerged as being radioprotective towards a mouse lymphocyte cell line. These compounds also protected human lymphoblastoid cells against radiation-induced apoptosis and were further tested in vitro and in vivo. In vivo, two injections of tetracycline prior to a lethal dose of radiation to the whole body (8 Gy) improved survival to 87.5% while all vehicle treated mice expired. The enhanced survival might be due to the protection of both lymphoid and myeloid stem/progenitor populations from radiation damage. Tetracycline injection post 8 Gy irradiation also improved the survival, but with lesser efficacy. In vitro pretreatment of human lymphoblastoid cells with tetracycline at 20 \#956;M reduced the foci formation of histone H2AX, indicating the protection from DNA double strand breaks. In addition, tetracycline does not interfere with radiotherapy of mouse lung tumor cells grafted in mice suggesting potential application for cancer radiotherapy. The mechanisms of tetracycline action in both normal tissue protection and sensitization of tumor cells are currently being investigated. This work was supported by UCLA\#8217;s Center for Biological Radioprotectors U19 AI067769/NIAID. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2298.