High-throughput screening identifies two classes of antibiotics as radioprotectors: tetracyclines and fluoroquinolones.

PURPOSE: 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 immunosuppression, 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. EXPERIMENTAL DESIGN: High-throughput screening of small-molecule libraries was done using viability of a murine lymphocyte line as a readout with further validation in human lymphoblastoid cells. The selected compounds were then tested for their ability to counter TBI lethality in mice. RESULTS: 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 classic mechanism of free radical scavenging but potentially through activation of the Tip60 histone acetyltransferase and altered chromatin structure. CONCLUSIONS: Tetracyclines and fluoroquinolones can be robust radioprotectors and mitigators of the hematopoietic system with potential utility in anticancer radiotherapy and radiation emergencies.

Breast core-needle biopsy: clinical trial of relaxation technique versus medication versus no intervention for anxiety reduction.

PURPOSE: To evaluate effectiveness of oral anxiolytic medication versus relaxation technique for anxiety reduction in women undergoing breast core-needle biopsy (CNB). MATERIALS AND METHODS: The institutional review board reviewed and approved the study. Informed consent was obtained from 143 consecutive women scheduled for breast CNB. Women were randomized as follows: no anxiety intervention (usual care group), relaxation therapy with an audiotape of classical music and ocean sounds during CNB (relaxation group), and 0.5-mg of alprazolam administered orally 15 minutes before CNB (medication group). Anxiety before, during, and 24 hours after the procedure was assessed with State-Trait Anxiety Inventory and self-reported visual analog scale from 0 (no anxiety) to 10 (worst anxiety). Data analysis was performed with statistical software. Descriptive statistics were computed for all variables. Group differences were determined with analysis of variance. Differences in mean values were assessed with Bonferroni multiple comparison procedure. Categorical demographic differences were assessed with chi(2) statistic. RESULTS: Preprocedural State-Trait Anxiety Inventory scores indicated that women were not inherently anxious: usual care group, score of 44.63; relaxation group, 45.74; and medication group, 49.1. Scores represented significantly elevated anxiety for women in all three groups when compared with the normative value of 35.12 (P < .0001), with no statistically significant differences between the scores of the three groups. Women in medication group reported significant reductions in anxiety (-44%) from levels determined before the procedure to levels determined during the procedure (P = .02) and significant reduction during the procedure when compared with changes in usual care (+15%) and relaxation (-8%) groups (P = .02). Women in all three groups reported significant reduction in anxiety from levels determined before the procedure to levels determined at 24 hours after it (P < .0001). There was no significant difference (P = .95) in 24-hour postprocedural anxiety levels among the three groups. CONCLUSION: Use of oral anxiolytic medication before breast CNB can significantly reduce anxiety women experience during the procedure.