Cellular signal transduction events as a function of linear energy transfer (LET).

In order to obtain a deeper insight into the molecular mechanism controlling the cellular response to high-linear energy transfer (LET) radiation, the number and size of pATM (S1981) and gamma-H2AX foci were compared in cultures of diploid human fibroblasts after exposure to charged particles of varying species, energy and LET at the NIRS-HIMAC-facility (Chiba, Japan). Particle LET ranged from 2.2 to 300 keV/mum, and a low fluence of 7.3 x 10(4) cm(-2) was chosen. Therefore, about 1 out of 7 nuclei was traversed by a particle. Doses and LET were verified with thermoluminescence detectors (LiF:Mg, Ti) evaluated according to the high temperature ratio method. Two hours after irradiation, fibroblasts were fixed and the subcellular distribution of pATM (S1981) and gamma-H2AX was visualised by immunofluorescence or histochemical staining using phosphorylation-specific antibodies. It was found that the number of pATM (S1981) foci per nucleus was higher after exposure to higher-LET particles. Irradiation with the two highest LET beams (Fe-ions, 197 and 300 keV/mum) gave a significant increase in the number of pATM foci, whereas ions with an LET lower than 30 keV/mum yielded similar numbers of pATM foci compared with unirradiated control samples. These data show that the early cellular response to high-LET radiation is modulated by the energy deposition of the particle. Therefore, the correlation between the microdosimetric aspect of energy deposition and biologic consequences at low radiation doses deserves further study.