Spectrum of Complex DNA Damages Depends on the Incident Radiation
ABSTRACT Ionizing radiation induces bistranded clustered damages--two or more abasic sites, oxidized bases and strand breaks on opposite DNA strands within a few helical turns. Since clusters are refractory to repair and are potential sources of double-strand breaks (DSBs), they are potentially lethal and mutagenic. Although induction of single-strand breaks (SSBs) and isolated lesions has been studied extensively, little is known about the factors affecting induction of clusters other than DSBs. To determine whether the type of incident radiation could affect the yields or spectra of specific clusters, we irradiated genomic T7 DNA, a simple 40-kbp linear, blunt-ended molecule, with ion beams [iron (970 MeV/nucleon), carbon (293 MeV/nucleon), titanium (980 MeV/nucleon), silicon (586 MeV/nucleon), protons (1 GeV/nucleon)] or 100 kVp X rays and then quantified DSBs, Fpg-oxypurine clusters and Nfo-abasic clusters using gel electrophoresis, electronic imaging and number average length analysis. The yields (damages/Mbp Gy(-1)) of all damages decreased with increasing linear energy transfer (LET) of the radiation. The relative frequencies of DSBs compared to abasic and oxybase clusters were higher for the charged particles-including the high-energy, low-LET protons-than for the ionizing photons.
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ABSTRACT: DNA methylation is an epigenetic mechanism that drives phenotype and that can be altered by environmental exposures including radiation. The majority of human radiation exposures occur in a relatively low dose range; however, the biological response to low dose radiation is poorly understood. Based on previous observations, we hypothesized that in vivo changes in DNA methylation would be observed in mice following exposure to doses of high linear energy transfer (LET) (56) Fe ion radiation between 10 and 100 cGy. We evaluated the DNA methylation status of genes for which expression can be regulated by methylation and that play significant roles in radiation responses or carcinogenic processes including apoptosis, metastasis, cell cycle regulation, and DNA repair (DAPK1, EVL, 14.3.3, p16, MGMT, and IGFBP3). We also evaluated DNA methylation of repeat elements in the genome that are typically highly methylated. No changes in liver DNA methylation were observed. Although no change in DNA methylation was observed for the repeat elements in the lungs of these same mice, significant changes were observed for the genes of interest as a direct effect and a delayed effect of irradiation 1, 7, 30, and 120 days post exposure. At delayed times, differences in methylation profiles among genes were observed. DNA methylation profiles also significantly differed based on dose, with the lowest dose frequently affecting the largest change. The results of this study are the first to demonstrate in vivo high LET radiation-induced changes in DNA methylation that are tissue and locus specific, and dose and time dependent. Environ. Mol. Mutagen. 55:266-277, 2014. © 2013 Wiley Periodicals, Inc.Environmental and Molecular Mutagenesis 04/2014; 55(3):266-77. DOI:10.1002/em.21832 · 2.55 Impact Factor
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ABSTRACT: Space exploration represents great challenge to astronauts’ health because of the uncertain risk of carcinogenesis caused by space radiation, in which high-charge and -energy (HZE) particles should be the most harmful components. Although there are a number of researches confirming that HZE particles have more severe biological effects including tumorigenesis than low-LET radiations, it is still very hard to accurately estimate the cancer risk of space HZE radiation due to the lack of suitable epidemiological data on exposures to low-dose HZE particle irradiation. Ground-based experiments on high-energy heavy ion accelerators might be appropriate complement for understanding the risk of space radiation. On the other hand, effective countermeasures to reduce the radiation damage are essential to manned space exploration. Up to now, shielding is still the most practical way to attenuate biological responses of space radiation. However, the knowledge on the biological effects of secondary particles produced by the interaction of HZE particles with shielding materials is required for space shielding design. This review will discuss the issues of space HZE particles and the biological effects of secondary particles produced by the interaction of space radiation and shielding materials.Rendiconti Lincei. Scienze Fisiche e Naturali 03/2014; 25(S1). DOI:10.1007/s12210-014-0288-y · 0.76 Impact Factor
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ABSTRACT: Study of heavy ion radiation-induced effects on mice could provide insight into the human health risks of space radiation exposure. The purpose of the present study is to assess the relative biological effectiveness (RBE) of (12)C and (28)Si ion radiation, which has not been reported previously in the literature. Female C57BL/6J mice (n = 15) were irradiated using 4-8 Gy of (28)Si (300 MeV/nucleon energy; LET 70 keV/μm) and 5-8 Gy of (12)C (290 MeV/nucleon energy; LET 13 keV/μm) ions. Post-exposure, mice were monitored regularly, and their survival observed for 30 days. The LD(50/30) dose (the dose at which 50 % lethality occurred by 30-day post-exposure) was calculated from the survival curve and was used to determine the RBE of (28)Si and (12)C in relation to γ radiation. The LD(50/30) for (28)Si and (12)C ion is 5.17 and 7.34 Gy, respectively, and the RBE in relation to γ radiation (LD(50/30)-7.25 Gy) is 1.4 for (28)Si and 0.99 for (12)C. Determination of RBE of (28)Si and (12)C for survival in mice is not only important for space radiation risk estimate studies, but it also has implications for HZE radiation in cancer therapy.Biophysik 05/2012; 51(3):303-9. DOI:10.1007/s00411-012-0418-9 · 1.58 Impact Factor