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Screening of antimicrobial agents for in vitro radiation protection and mitigation capacity, including those used in supportive care regimens for bone marrow transplant recipients

Epperly, MW and Franicola, D and Shields, D and Rwigema, JC and Stone, B and Zhang, X and Mcbride, W and Georges, G and Wipf, P and Greenberger, JS (2010) Screening of antimicrobial agents for in vitro radiation protection and mitigation capacity, including those used in supportive care regimens for bone marrow transplant recipients. In Vivo, 24 (1). 9 - 19. ISSN 0258-851X

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Antibiotic and antifungal agents used in supportive care regimens for bone marrow transplantation recipients contribute to a significant dose-modifying effect of otherwise lethal total body irradiation. To determine whether drugs used in supportive care and other commonly used antibiotics such as tetracycline function as radiation protectors or damage mitigators in vitro, 13 drugs were tested for radiation protection and radiation damage mitigation of 32D cl 3 hematopoietic progenitor cells in clonagenic survival curves in vitro. Antibiotic/Antifungal agents including cilastatin, amikacin, ceftazidine, vancomycin, tetracycline, doxycycline, ciprofloxacin, metronidazole, methacycline, minocycline, meclocycline, Oxytetracycline and rolitetracycline were added in 1, 10, or 100 micromolar concentrations to murine interleukin-3-dependent hematopoietic progenitor cell line 32D cl 3 cells either before or after irradiation of 0 to 8 Gy. Control irradiated 32D cl 3 cells showed radiosensitivity comparable to freshly explanted mouse marrow hematopoietic progenitor cells (D0 1.1 ±0.1 Gy, Ñ 15±0.4). Positive control GS-nitroxide JP4-039 (known radiation mitigator) treated 32D cl 3 cells were radioresistant (D0 1.2±0.1, Ñ 5.8±2.4 (p=0.009)). Of the 13 drugs tested, tetracycline was found to be a significant radiation mitigator (D0 0.9±0.1, Ñ 13.9±0.4 (p=0.0027)). Thus, the radiation dose-modifying effect of some antibiotics, but not those currently used in the supportive care (antibiotic/antifungal regimens) for marrow transplant patients, may act as radiation damage mitigators for hematopoietic cells as well as decreasing the growth and inflammatory response to microbial pathogens.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Epperly, MW
Franicola, D
Shields, D
Rwigema, JC
Stone, B
Zhang, Xxichen@pitt.eduXICHEN
Mcbride, W
Georges, G
Wipf, Ppwipf@pitt.eduPWIPF
Greenberger, JSjoelg@pitt.eduJOELG
Date: 1 January 2010
Date Type: Publication
Journal or Publication Title: In Vivo
Volume: 24
Number: 1
Page Range: 9 - 19
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 0258-851X
MeSH Headings: Animals; Anti-Bacterial Agents--pharmacology; Antifungal Agents--pharmacology; Bone Marrow Transplantation; Cell Line; Cell Survival--drug effects; Cell Survival--radiation effects; Dose-Response Relationship, Radiation; Hematopoietic Stem Cells--drug effects; Hematopoietic Stem Cells--pathology; Hematopoietic Stem Cells--radiation effects; Mice; Radiation Injuries, Experimental--pathology; Radiation Injuries, Experimental--prevention & control; Radiation-Protective Agents--pharmacology
Other ID: NLM NIHMS269606, NLM PMC3039923
PubMed Central ID: PMC3039923
PubMed ID: 20133970
Date Deposited: 23 Sep 2014 14:48
Last Modified: 26 Sep 2022 16:24


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