NGS Detects Extensive Genomic Alterations in Survivors of Irradiated Normal Human Fibroblast Cells.

It is thought that cells surviving ionizing radiation exposure repair DNA double-strand breaks (DSBs) and restore their genomes. However, the recent biochemical and genetic characterization of DSB repair pathways reveals that only homologous recombination (HR) can function in an error-free manner and that the non-homologous end joining (NHEJ) pathways canonical NHEJ (c-NHEJ), alternative end joining (alt-EJ), and single-strand annealing (SSA) are error-prone, and potentially leave behind genomic scars and altered genomes. The strong cell cycle restriction of HR to S/G2 phases and the unparalleled efficiency of c-NHEJ throughout the cell cycle, raise the intriguing question as to how far a surviving cell "reaches" after repairing the genome back to its pre-irradiation state.

Dose-Dependent Transmissibility of Chromosome Aberrations in Human Lymphocytes at First Mitosis. II. Biological Effectiveness of Heavy Charged Particles Versus Gamma Rays.

Chromosome aberrations (CAs) are large scale structural rearrangements to the genome that have been used as a proxy endpoint of mutagenic and carcinogenic potential. And yet, many types of CAs are incapable of causing either of these effects simply because they are lethal. Using 24-color multi-fluor combinatorial painting (mFISH), we examined CAs in normal human lymphocytes exposed to graded doses of 1 GeV/nucleon accelerated 56Fe ions and 662 keV 137Cs gamma rays.

Dose-dependent Transmissibility of Chromosome Aberrations at First Mitosis after Exposure to Gamma Rays. I. Modeling and Implications Related to Risk Assessment.

The relationship between certain chromosomal aberration (CA) types and cell lethality is well established. On that basis we used multi-fluor in situ hybridization (mFISH) to tally the number of mitotic human lymphocytes exposed to graded doses of gamma rays that carried either lethal or nonlethal CA types. Despite the fact that a number of nonlethal complex exchanges were observed, the cells containing them were seldom deemed viable, due to coincident lethal chromosome damage.

Robbing Peter to Pay Paul: Competition for Radiogenic Breaks During Rejoining Diminishes Curvature in the Dose Response for Simple Chromosome Exchanges.

The large majority of chromosome damage produced by ionizing radiations takes the form of exchange aberrations. For simple exchanges between two chromosomes, multi-fluor fluorescence in situ hybridization (mFISH) studies confirm that the dose response to X rays or gamma rays is quasilinear with dose. This result is in seeming conflict with generalized theories of radiation action that depend on the interaction of lesions as the source of curvature in dose-response relationships.

Host antibacterial defense of 6-10 Gy γ-irradiated mice subjected to lentiviral vector-based Gas5 gene therapy.

Gut bacteria-associated sepsis is a serious concern in patients with gastrointestinal acute radiation syndrome (GIARS). In our previous studies, all mice exposed to 8 Gy of whole body γ-irradiation (8 Gy GIARS-mice) died by sepsis stemming from bacterial translocation. M1Mϕ located in the bacterial translocation site (i.