Subject(s)
Cell Cycle/genetics , Cell Cycle/radiation effects , Chromosomal Instability/genetics , Chromosomal Instability/radiation effects , DNA Damage/genetics , DNA Repair/genetics , Models, Genetic , Animals , Computer Simulation , DNA Repair/radiation effects , Dose-Response Relationship, Radiation , Humans , Radiation DosageABSTRACT
One of the quantitative methods used in DNA repair research is a measurement of the size-distribution of DNA fragments at different times following cell irradiation. The aim of the present study was to evaluate the relationship between the experimentally observed size-distributions of DNA fragments and the parameters of doublestrand break (DSB) repair. A biophysical model of DNA DSB repair in chromosomal DNA including DSB clusters repair was proposed. Complex shapes of (1) DNA fragments distribution at different repair times, (2) rejoining kinetics for DNA fragments in different length intervals, (3) total fragments rejoining kinetics were simultaneously described with rates of DSB repair different for active/inactive chromatin compartments.
Subject(s)
DNA Breaks, Double-Stranded/radiation effects , DNA Repair/radiation effects , Gamma Rays , Linear Energy Transfer , Models, Genetic , Biophysical Phenomena , Biophysics , Chromatin/chemistry , Chromosome Breakage/radiation effects , DNA Fragmentation/radiation effects , Electrophoresis, Gel, Pulsed-Field , Fibroblasts/radiation effects , Humans , Kinetics , Monte Carlo Method , Time FactorsABSTRACT
Methodological problems arise on the way of radiation carcinogenesis modelling with the incorporation of radiobiological and cancer biology mechanistic data. The results of biophysical modelling of different endpoints [DNA DSB induction, repair, chromosome aberrations (CA) and cell proliferation] are presented and applied to the analysis of RBE-LET relationships for radiation-induced neoplastic transformation (RINT) of C3H/10T1/2 cells in culture. Predicted values for some endpoints correlate well with the data. It is concluded that slowly repaired DSB clusters, as well as some kind of CA, may be initiating events for RINT. As an alternative interpretation, it is possible that DNA damage can induce RINT indirectly via epigenetic process. A hypothetical epigenetic pathway for RINT is discussed.
