Induction of DNA Double-Strand Breaks by 1 H and 4 He Ions in Primary Human Skin Fibroblasts in the LET Range of 8 to 124 keV/mm

Abstract

Yields of DNA double-strand breaks were determined in primary human skin fibroblasts exposed to 1H and 4He ions at various linear energy transfers (LETs) and to 15 MeV electrons as the reference radiation. The values obtained for the relative biological effectiveness (RBE) were 2.03, 1.45 and 1.36 for 1H ions at LETs of 35, 23 and 7.9 keV/microm, respectively, and 1.2, 1.18, 1.38 and 1.31 for 4He ions at LETs of 124, 76, 35 and 27 keV/microm, respectively. The data were obtained using pulsed-field gel electrophoresis of DNA released from cells using the chromosomes of the yeast Saccharomyces cerevisiae as length markers and fitting the experimental mass distributions of fragmented DNA to those obtained by computer simulation of the random breakage of human chromosomes. The RBE values for induction of DSBs in mammalian cells cannot be fitted to a common RBE-LET relationship for electrons and 1H, 4He and light ions. Comparison of the RBEs for mammalian cells with the corresponding RBEs obtained for yeast cells shows similar RBEs of electrons for yeast and mammalian cells; however, for 4He and light ions in the LET range of 100 to 1000 keV/microm, the RBEs for yeast are significantly higher compared with mammalian cells. These characteristics of the RBE-LET relationships for yeast and mammalian cells are attributed to the fraction of small DNA fragments induced by particles when traversing the higher-order chromatin structures which are different to some extent in these two cell types.

Mutation induction by inhaled radon progeny modeled at the tissue level

“…For a-particles, different DSB induction rates can be found in the literature. According to Frankenberg et al (1999), 42 Gy -1 is a reasonable value for human cells. Based on other measurements (Rydberg et al 2002), approximately 66 Gy -1 can be assumed.…”

“…In this case, the parameters are the following: DSB induction rate (b) is 107 Gy -1 (Claesson et al 2007) and b is set to 0.285 in (4) (Hei et al 1997). In the second case, parameters are selected so that the significance of cell inactivation in mutation induction is maximal as compared to the (Frankenberg et al 1999), and b is 0.587 (Soyland and Hassfjell 2000). Figure 12 illustrates the surviving fractions as a function of tissue dose by the two parameter sets.…”

Ionizing radiation biomarkers for potential use in epidemiological studies

“…These include techniques such as alkaline or neutral filter elution [103,104], alkaline unwinding [105,106], sucrose gradient centrifugation [107][108][109] or pulsed field gel electrophoresis [110][111][112][113]. However the utility of such techniques for molecular epidemiological studies investigating low doses effects is limited as none can be used to investigate DNA damage after exposures to doses under 2 Gy and at the single cell level.…”

DSB repair model for mammalian cells in early S and G1 phases of the cell cycle: Application to damage induced by ionizing radiation of different quality

“…trend was also observed for helium-3 and helium-4 beams. In general, in mammalian cells, the RBE of induction of DSB by ions is approximately independent of the particle LET [32,[42][43][44]. Table 3 presents the calculated frequency of different types of damage according to the complexity of the DNA damage (Fig.…”