Genomic instability induced by high and low LET ionizing radiation.
Genomic instability is the increased rate of acquisition of alterations in the mammalian genome, and includes such diverse biological endpoints as chromosomal destabilization, aneuploidy, micronucleus formation, sister chromatid exchange, gene mutation and amplification, variations in colony size, reduced plating efficiency, and cellular transformation. Because these multiple endpoints persist long after initial radiation exposure, genomic instability has been proposed to operate as a driving force contributing to genetic plasticity and carcinogenic potential. Many of these radiation-induced endpoints depend qualitatively and quantitatively on genetic background, dose and LET. Differences in the frequency and temporal expression of chromosomal instability depend on all three of the foregoing factors. On the other hand, many of these endpoints appear independent of dose and show bystander effects, implicating non-nuclear targets and epigenetic regulatory mechanisms. The present work will survey results concerning the LET dependence of genomic instability and the role of epigenetic mechanisms, with a particular emphasis on the endpoint of chromosomal instability.
Limoli
C L
CL
Department of Radiology, University of California, San Francisco 94143-0750, USA.
Ponnaiya
B
B
Corcoran
J J
JJ
Giedzinski
E
E
Kaplan
M I
MI
Hartmann
A
A
Morgan
W F
WF
D000818:Animals; D002468:Cell Physiological Phenomena / Q000528:radiation effects; D002869:Chromosome Aberrations; D002873:Chromosome Fragility; D002875:Chromosomes / Q000528:radiation effects*; D006224:Cricetinae; D016678:Genome; D006801:Humans; D018499:Linear Energy Transfer; D051379:Mice; D009369:Neoplasms / Q000209:etiology; D011839:Radiation, Ionizing