Attenuation of radiation-induced genomic instability by free radical scavengers and cellular proliferation.
To investigate the mechanisms of radiation-induced chromosomal instability, cells were irradiated in the presence of the free radical scavengers DMSO, glycerol, or cysteamine, in the presence of DMSO while frozen, or held in confluence arrest post-irradiation to permit cells to repair potentially lethal DNA damage. Clones derived from single progenitor cells surviving each treatment were then analyzed for the subsequent development of chromosomal instability. The presence of scavengers (+/- freezing) during irradiation, and the recovery from potentially lethal damage after irradiation led to an increase in cell survival that was accompanied by a decrease in the initial yield of chromosomal rearrangements. Furthermore, analysis of over 400 clones and 80,000 metaphases indicates that these same treatments reduced the incidence of instability at equitoxic doses when compared to controls irradiated in the absence of scavengers at ambient temperature. Results suggest that preventing reactive species from damaging DNA, promoting chemical repair of ionized DNA intermediates, or allowing enzymatic removal of genetic lesions, represent measures that reduce the total burden of DNA damage and reduce the subsequent onset of radiation-induced genomic instability.
Limoli
C L
CL
Department of Radiology, University of California, San Francisco, CA, USA. limoli@itsa.ucsf.edu
Kaplan
M I
MI
Giedzinski
E
E
Morgan
W F
WF
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D002478:Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D003543:Cysteamine / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005990:Glycerol / Q000494:pharmacology; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D016166:Free Radical Scavengers; D011837:Radiation-Protective Agents; D003543:Cysteamine; D005990:Glycerol; D004121:Dimethyl Sulfoxide