Telomere length in mammalian cells exposed to low- and high-LET radiations.

Telomeres are specialised nucleoprotein complexes that serve as protective caps of linear eukaryotic chromosomes. The loss of the ends of the chromosomes due to these un-rejoined double strand breaks (DSBs) may not be lethal to the cell, but may instead result in the loss of functional telomeres, chromosome fusions and initiation of breakage/fusion/bridge cycle-induced chromosome instability. The telomeres also participate in the process of DNA repair, as evidenced by 'de novo' synthesis of telomere repeats at DSBs and by the capacity of telomeres to binding the essential components of the DNA repair machinery. Based on the observation that high-LET radiations efficiently induce chromosome aberrations, it was tested whether protons were able to affect telomere structure. Human primary fibroblasts (HFFF2) and mouse embryonic fibroblasts (MEFs) were irradiated with 4 Gy of 3 MeV protons at the radiobiology facility of the INFN-LNL. Experiments with X rays were also carried out. Cells were fixed after either 24 h or 15 d from treatment. A difference in average telomere length, measured by quantitative fluorescence in situ hybridisation (Q-FISH), between X rays and protons treatment was observed. X rays are able to modify telomere length in HFFF2 harvested at a later time. On the other hand, 3 MeV low-energy protons induced, both in HFFF2 and in MEFs, a significant increase in telomere length at short as well as at long harvesting time periods from treatment. These results seem to indicate that lesions characterised by different complexity, as those expected after low-energy protons and those induced by damage similar to that induced by sparsely ionising radiation, are able to modulate telomere elongation at different time periods.