RESUMO
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.
Assuntos
Quebras de DNA de Cadeia Dupla/efeitos da radiação , Reparo do DNA/efeitos da radiação , Raios gama , Transferência Linear de Energia , Modelos Genéticos , Fenômenos Biofísicos , Biofísica , Cromatina/química , Quebra Cromossômica/efeitos da radiação , Fragmentação do DNA/efeitos da radiação , Eletroforese em Gel de Campo Pulsado , Fibroblastos/efeitos da radiação , Humanos , Cinética , Método de Monte Carlo , Fatores de TempoRESUMO
Chromosomal aberrations (CAs) are regarded as one of the most sensitive biological indicators of genetic alterations. The aberration frequency is routinely determined in the first metaphase. Yet, the data interpretation can be complicated due to radiation induced mitotic delays. To investigate the effect of delays on CA frequency in the first mitosis, human lymphocytes were irradiated with X rays and Giemsa detectable CAs were measured at different sampling times. Besides, a computer simulation was performed reproducing the main effects under investigation, that is, CA induction and cell progression through the mitotic cycle. The CA formation model takes into account the structural organisation of interphase chromosomes in a lymphocyte nucleus, DNA double-strand break (DSB) induction and their rejoining/misrejoining. Lymphocyte transition through the cell cycle was simulated by a Monte Carlo technique. The delay was proposed to result from DNA DSBs. The predicted ratios of first/second/third cycle metaphases agree with the experimental data for control and irradiated samples. Both experimental and calculated CA frequencies in the first mitosis were nearly time-independent. This was proposed to result from de-synchronisation of the lymphocyte population.
Assuntos
Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Aberrações Cromossômicas/efeitos da radiação , Cromossomos/genética , Cromossomos/efeitos da radiação , Leucócitos Mononucleares/fisiologia , Leucócitos Mononucleares/efeitos da radiação , Modelos Genéticos , Células Cultivadas , Simulação por Computador , Relação Dose-Resposta à Radiação , Feminino , Humanos , Doses de RadiaçãoRESUMO
We describe our studies of the generation of plasma wake fields by a relativistic electron bunch and of phasing between the longitudinal and transverse fields in the wake. The leading edge of the electron bunch excites a high-amplitude plasma wake inside the overdense plasma column, and the acceleration and focusing wake fields are probed by the bunch tail. By monitoring the dependence of the acceleration upon the plasma's density, we approached the beam-matching condition and achieved an energy gain of 0.6 MeV over the 17 mm plasma length, corresponding to an average acceleration gradient of 35 MeV/m. Wake-induced modulation in energy and angular divergence of the electron bunch are mapped within a wide range of plasma density. We confirm a theoretical prediction about the phase offset between the accelerating and focusing components of plasma wake.
