Repair of DNA double-strand breaks and its effect on RBE.
DNA double-strand breaks (DSB) are induced linearly with absorbed dose both for sparsely and densely ionizing radiations. By enzymatic repair the linear relationship between the number of DSB and absorbed dose is converted into a non linear one. Furthermore, the RBE-values of high LET radiations for residual DSB increase with increasing amount of DSB repair especially in the low dose range. Unrepaired and/or misrepaired DSB are supposed to be responsible for chromosomal aberrations, cell killing, oncogenic cell transformation and gene mutation. At low doses, for these endpoints much higher RBE-values than those for initial DSB are observed. However, with increasing doses the RBE-values for these endpoints approach those for initial DSB. These observations are likely to be interpreted using the following two parameters of the energy deposition structure:  1. The distribution of clusters with respect to their size at the nm-scale and to the number of ionizations per cluster (cluster distribution).  2. The distribution of distances between clusters of definite size and with definite number of ionizations (distance distribution of clusters).  For the induction of DSB solely the ionization density in clusters of nm-dimensions (i.e. the cluster distribution) is important. For unrepaired or misrepaired DSB (responsible for chromosome aberrations, cell killing, oncogenic cell transformation and gene mutation) both the cluster distribution and the distance distribution of clusters are relevant. At low doses the distance distribution of clusters along a single particle track determines the RBE-value. However, with increasing dose the distribution of clusters produced by all particles traversing the cell nucleus becomes increasingly determinant. Here, solely the cluster distribution is important as it is the case for the induction of DSB.
Frankenberg
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Abteilung Klinische Strahlenbiologie und Klinische Strahlenphysik, Universitat Gottingen, Germany.
D000512:Alpha Particles; D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004271:DNA, Fungal / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D005347:Fibroblasts; D006801:Humans; D018499:Linear Energy Transfer; D009154:Mutation; D017785:Photons; D011839:Radiation, Ionizing; D012062:Relative Biological Effectiveness; D015003:Yeasts / Q000166:cytology / Q000235:genetics / Q000528:radiation effects
D004271:DNA, Fungal; D004247:DNA