Genetic action of radiation with different physical characteristics on mammalian cells

摘要

The induction of hypoxanthine-guanine-phosphoribosyl-transferase (HPRT) mutations and the survival rate of Chinese hamster cells were investigated after exposure to accelerated He-4 and C-12 ions with varying linear energy transfer (LET) (20-360 keV/mum) and to gamma rays. The power law was found for the mutation induction rate as a function of the radiation dose with LET up to 50 keV/mum. The dependence transforms into a linear one at higher LET values. The RBE of heavy charged ions increases with the LET of ions to maximal values at 80-100 keV/mum. The RBE values for the induction of mutations and chromosomal aberrations amount to 4.8-5.0 and are twice as high as the values corresponding to the cell-survival criterion (2.3-2.9). A high heterogeneity and chromosomal instability in aneuploidy and chromosomal-aberration levels were observed in spontaneous mutants and in those induced by protons (LET of 0.218 keV/mum), N-14 ions (LET of similar to77 keV/mum), and gamma rays. The chromosomal instability was highest for spontaneous mutants and decreased with increasing LET. The metabolic hypothesis for the chromosomal instability is discussed. The regularities in the formation of unstable chromosomal aberrations in human-blood lymphocytes were studied after exposure to protons, 12C, Mg-24, and N-14 ions (LET of 0.218, similar to12, 42.7, and similar to77 keV/mum, respectively), and gamma rays. The rate of aberrations increased with the dose and radiation LET. The RBE values were 1.0. 1.2-1.3, 1.4-1.7, and 2.0-2.2 for protons, C-12, Mg-24, and N-14 ions, respectively. The FISH analysis of stable chromosomal aberrations (translocations) revealed a high efficiency of N-14 ions (RBE of similar to3.0). According to all cytogenetic tests, there were no essential differences between the efficiency of protons and gamma rays. The dose dependence of the rate of production of cells with chromosomal aberrations after exposure of human lymphocytes, Chinese hamster cells, and human melanoma cells to gamma rays and their adaptive response were studied in the dose range of 0.01-1 Gy. For all types of cells, a nonlinear dose-effect dependence was revealed for cells with chromosomal aberrations. This dependence is characterized by a hypersensitivity of cells at doses of 0.01-0.2 Gy and an induced radioresistance at doses above 0.5 Gy. The possible mechanisms involved in this phenomenon are discussed.