ABSTRACT
Double-strand breaks (DSBs) are the most critical radiation-induced lesions, because they result in the fragmentation of the DNA molecule and because a single unrepaired DSB may lead to cell death. We present the results of radiation-induced fragmentation of plasmid DNA analyzed by atomic force microscopy (AFM) to allow the visualization of individual DNA molecules. Linear PhiX174 plasmid DNA was exposed to a wide range of doses of low-LET X rays and high-LET carbon, nickel and uranium ions. The induced DNA fragments were detected and measured based on the recorded AFM images and fragment length distributions were derived for each radiation type and dose. The results show a dose- and radiation type-dependent DNA fragmentation with a significantly larger fraction of short fragments produced by high-LET radiation compared to X rays. This can be considered as experimental evidence of DSB clustering due to inhomogeneous energy deposition at the level of the plasmid DNA molecule. Additionally, the experimentally derived fragment profiles were compared and found to be in agreement with the prediction of a model simulating the fragmentation of DNA molecules induced by radiation.
Subject(s)
DNA Damage , DNA/chemistry , DNA/ultrastructure , Microscopy, Atomic Force/methods , Models, Chemical , Models, Molecular , Computer Simulation , DNA/radiation effects , Dose-Response Relationship, Radiation , Nucleic Acid Conformation/radiation effects , Radiation DosageABSTRACT
An improvement of the Local Effect Model (LEM) is presented which takes clustered DNA damage into account. Single strand breaks (SSBs) and double strand breaks (DSBs) are distributed stochastically onto the DNA molecule and additional DSBs are recorded. Consideration of this additional damage leads to a modification of the underlying photon survival curve at high doses. As a consequence of the new approach, the ratio of maximum relative biological effectiveness (RBE) values to minimum RBEs is increased. This can be understood in terms of a higher radiation effect resulting from the cluster damage at high local doses. We find that the extended LEM including cluster effects reproduces experimental data for V79 cells significantly better than the original LEM.
Subject(s)
Cell Survival/radiation effects , DNA Damage , Fibroblasts/physiology , Fibroblasts/radiation effects , Linear Energy Transfer , Models, Biological , Radiotherapy Planning, Computer-Assisted/methods , Animals , Cell Line , Cluster Analysis , Computer Simulation , Cricetinae , DNA/radiation effects , Humans , Radiometry/methods , Radiotherapy Dosage , Radiotherapy, Conformal/methods , Scattering, RadiationABSTRACT
We report on collective nonlinear dynamics in an optical lattice formed inside a high finesse ring cavity in a so far unexplored regime, where the light shift per photon times the number of trapped atoms exceeds the cavity resonance linewidth. We observe bistability and self-induced squeezing oscillations resulting from the retroaction of the atoms upon the optical potential wells. We can well understand most of our observations within a simplified model assuming adiabaticity of the atomic motion. Nonadiabatic aspects of the atomic motion are reproduced by solving the complete system of coupled nonlinear equations of motion.
