Screening of antimicrobial agents for in vitro radiation protection and mitigation capacity, including those used in supportive care regimens for bone marrow transplant recipients.
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 (D(0) 1.1+/-0.1 Gy, N 1.5+/-0.4). Positive control GS-nitroxide JP4-039 (known radiation mitigator) treated 32D cl 3 cells were radioresistant (D(0) 1.2+/-0.1, N 5.8+/-2.4 (p=0.009)). Of the 13 drugs tested, tetracycline was found to be a significant radiation mitigator (D(0) 0.9+/-0.1, N 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.
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Michael W
MW
Epperly
Darcy
D
Franicola
Donna
D
Shields
Jean-Claude
JC
Rwigema
Brandon
B
Stone
Xichen
X
Zhang
William
W
McBride
George
G
Georges
Peter
P
Wipf
Joel S
JS
Greenberger
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D016026:Bone Marrow Transplantation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D011837:Radiation-Protective Agents