title: GANRA-5 protects both cultured cells and mice from various radiation types by functioning as a free radical scavenger.
abstract: The radio-protective effects of the oxazolone derivative chemical compound 4-(4-methoxy-3-methoxyphenyl-methyl)-2-phenyl- 5(4H)-oxazolone (GANRA-5) against different types of radiation including X-rays, carbon ion beams, microwaves and ultraviolet light (UV) were studied. Cell proliferation/cytotoxicity assay and colony-forming assay were conducted to evaluate the toxicity of GANRA-5. To test its influence on the induction of double-stranded break (DSB) formation and genomic instability, γH2AX focus-forming assay as well as cytokinesis-block micronucleus assay was utilized. Our results indicate that GANRA-5 exhibits low toxicity, while providing high radio-protective effects for MRC-5 cells against different types of radiation. We also found that GANRA-5 acts as a free radical scavenger. Our animal studies provided evidence that GANRA-5 significantly increases the survival rate of mice after X-ray irradiation. Analyses of hemogram, visceral index and detection of superoxide dismutase (SOD) and malondialdehyde (MDA) in the viscera indicate both low toxicity of GANRA-5, combined with its ability to shield radiation risk. In conclusion, our results suggest that GANRA-5 has the potential to be used as a safe and efficient radio-protectant.
authors.affiliation: Department of Space Radiobiology, Institute of Modern Physics, Chinese Academy of Sciences , Lanzhou , P. R. China.
authors.forename: H
authors.initials: H
authors.lastname: Pei
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: W
authors.initials: W
authors.lastname: Hu
authors.forename: M
authors.initials: M
authors.lastname: Zhu
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D042822:Genomic Instability / Q000187:drug effects / Q000528:radiation effects*; D020450:Heavy Ions / Q000009:adverse effects; D006657:Histones; D006801:Humans; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D015162:Micronucleus Tests; D008872:Microwaves / Q000009:adverse effects; D010081:Oxazolone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000032:analysis; D014466:Ultraviolet Rays / Q000009:adverse effects; D014965:X-Rays / Q000009:adverse effects
chemical_list: D016166:Free Radical Scavengers; D006657:Histones; D011837:Radiation-Protective Agents; C475961:gamma-H2AX protein, mouse; D010081:Oxazolone; D008315:Malondialdehyde; D013482:Superoxide Dismutase