Induction of mutations in mammalian cells after exposure to ionizing radiation (IR) and their propagation in time remains to be of great interest of the fundamental radiation research. In the connection with planned long-term space flights beyond the Earth’s magnetosphere and the still increasing use during cancer treatment, the attention has been recently shifted to the study of high-charge and high-energy ions which represent a substantial part of the galactic cosmic ray spectra.
This work focuses on the study of delayed genetic effects in Chinese hamster V79 cells after exposure to radiation with high values of linear energy transfer (LET). Emphasis is given to the induction of mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT) after prolonged expression times (ET; period of cell growth from irradiation until reseeding on a selective medium) as well as to the analysis of structural alterations in the HPRT gene of IR induced mutants. Various irradiation conditions were used during this study: accelerated heavy ions 18O (E = 35.2 MeV/n ), 20Ne (E = 47.7 MeV/n and 51.8 MeV/n), and 11B (E = 32.4 MeV/n), with LET in the range from 49 to 149 keV/µm and also electromagnetic gamma radiation of 60Co with estimated LET ~ 0.23 keV/µm. The induced HPRT mutant colonies were detected in irradiated cells during every cell culture recultivation (usually every 3 days) up to approximately 40 days (70 – 80 generations) after irradiation. Unique mutant colonies were isolated regularly and their DNA extracted and analyzed. It was found that the mutant fraction (MF) maximum is reached at different ET in dependence on the used IR. In the LET interval tested, the position of MF maximum was moving toward longer ET with higher LET. Substantial differences in mutational spectra (on the exon level) were found between the mutants induced either by sparsely or by densely ionizing radiation. Moreover, correlation between the MF maximum and total deletion maximum was observed at similar ET after irradiation.
A hypothesis about the IR induced delayed genetic effects being a manifestation of genomic instability is discussed. It is speculated that the LET dependent effects are related to the different energy deposition structure along the particle track. However, the exact mechanisms involved in the observed phenomena and induction and propagation of genomic instability are yet to be elucidated.