Biophysical Basis of Ionizing Radiation

Predicting DNA damage foci and their experimental readout with 2D microscopy: a unified approach applied to photon and neutron exposures

“…It has to be mentioned here that complex DNA damage can be of various types. We here used the definition of DSB cluster as a DNA lesion comprising at least 2 DSBs within 25 bp, closely following the definition of DSB++, given in 52,53 and already used in several works 3,42 . Different definitions could have been adopted (as e .…”

“…In terms of DNA damage induction, for each condition we considered the following simulation output: (i) the total number of DSBs and DSB clusters, where a cluster is defined as the occurrence of two or more DSBs within a genomic distance of 25 bp 52,53 ; (ii) the spatial distributions of both DSBs and DSB clusters. Spatial distributions are given by PARTRAC on a voxelized grid: the genetic material in the nucleus is built by 50 × 50 × 50 nm 3 cubic elements, each containing ~4.8 to 6 kbp in form of a chromatin fiber.…”

A Mathematical Radiobiological Model (MRM) to Predict Complex DNA Damage and Cell Survival for Ionizing Particle Radiations of Varying Quality

“…, where v i is the electron's velocity and l i its elastic mean free path in the medium, with the values D 1 = 0.265 nm 2 /fs, D 2 = 0.057 nm 2 /fs and the average lifetimes of the two generations' electrons, respectively, τ 1 = 0.64 fs and τ 2 = 15.3 fs (mean free path data have been taken from [146,147]). We have considered time t 50 fs as that of integration over these equations, since at this fraction of time the transport of these electrons is over [49,130]. This time is shorter than that of the formation of hydroxyl radicals, but by the time OH • are formed there are no more active sources.…”

Genome-based, mechanism-driven computational modeling of risks of ionizing radiation: The next frontier in genetic risk estimation?

“…The solutions of the equations provide individual protein activity kinetics and overall repair kinetics, and these can be compared with experimental measurements (usually rate of repair of DSBs, post-irradiation, using PFGE in the dose range of 40-100 Gy). While most of the models dealt with the NHEJ pathway (e.g., [41,42,44,49,63,64,[111][112][113][114], some have also considered single-strand annealing (SSA) [115]; microhomology-mediated end-joining (MMEJ) [48]; application to high LET radiations [48]; and base-excision-repair (BER) [46].…”

“…However, in the context of theoretical biophysical studies, several investigators have used models mostly of interphase nuclei of mammalian somatic cells that vary in complexity from cylinders representing simple linear segments of DNA to higher order structures such as nucleosomes, chromatin fiber, DNA loops and chromosomal domains (e.g., [37,38,[48][49][50][51][52][53][54][55]). Models of mitotic nuclei have also been published [56,57].…”