RESUMO
PURPOSE: Linear energy transfer (LET) plays an important role in radiation response. Recently, the radiation-induced nucleo-shuttling of ATM from cytoplasm to the nucleus was shown to be a major event of the radiation response that permits a normal DNA double-strand break (DSB) recognition and repair. Here, we aimed to verify the relevance of the ATM nucleo-shuttling model for high-LET particles and various radiation types. METHODS AND MATERIALS: ATM- and H2AX-immunofluorescence was used to assess the number of recognized and unrepaired DSB in quiescent fibroblast cell lines exposed to x-rays, γ-rays, 9- and 12-MeV electrons, 3- and 65-MeV protons and 75-MeV/u carbon ions. RESULTS: The rate of radiation-induced ATM nucleo-shuttling was found to be specific to each radiation type tested. By increasing the permeability of the nuclear membrane with statin and bisphosphonates, 2 fibroblast cell lines exposed to high-LET particles were shown to be protected by an accelerated ATM nucleo-shuttling. CONCLUSIONS: Our findings are in agreement with the conclusion that LET and the radiation/particle type influence the formation of ATM monomers in cytoplasm that are required for DSB recognition. A striking analogy was established between the DSB repair kinetics of radioresistant cells exposed to high-LET particles and that of several radiosensitive cells exposed to low-LET radiation. Our data show that the nucleo-shuttling of ATM provides crucial elements to predict radiation response in human quiescent cells, whatever the LET value and their radiosensitivity.
Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Transferência Linear de Energia , Tolerância a Radiação , Proteínas Mutadas de Ataxia Telangiectasia/genética , Carbono/química , Linhagem Celular , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Sobrevivência Celular , Dano ao DNA , Fibroblastos/efeitos da radiação , Raios gama , Histonas/metabolismo , Humanos , Íons , Cinética , Microscopia de Fluorescência , Permeabilidade , Prótons , RadiometriaRESUMO
We have measured universal conductance fluctuations in the metallic spin glass Ag:Mn as a function of temperature and magnetic field. From this measurement, we can access the phase coherence time of the electrons in the spin glass. We show that this phase coherence time increases with both the inverse of the temperature and the magnetic field. From this, we deduce that decoherence mechanisms are still active even deep in the spin glass phase.