A role for genomic instability in cellular radioresistance?
Inherent cellular radioresistance plays a critical role in the failure of radiotherapy. Although the consequences of radioresistance are well known, the molecular, biological, and cellular bases of radioresistance remain a mystery. We propose that genomic instability, the increased rate of acquisition of alterations in the mammalian genome, can directly modulate cells' sensitivity to radiation. In particular, destabilization of chromosomes occurring as a consequence of genomic instability may result in enhanced 'plasticity of the genome'. This increased plasticity of the genome allows cells to better adapt to changes in local environment(s) during tumor progression, or improve cell survival following exposure to DNA damage encountered during radiotherapy protocols, thereby contributing to radioresistant cell populations found in tumors both before and after radiotherapy.
Morgan
W F
WF
Laboratory of Radiobiology and Environmental Health, University of California, San Francisco, USA.
Murnane
J P
JP
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D002869:Chromosome Aberrations; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D016678:Genome; D015894:Genome, Human; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000532:radiotherapy*; D011836:Radiation Tolerance; D016615:Telomere / Q000235:genetics / Q000528:radiation effects