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It has been well established that the bone marrow (BM) is a radiosensitive tissue, but the radiosensitivity of the heart is poorly understood. In this study, we investigated the comparative effects of ²⁸Silicon (²⁸Si) ions (one type of heavy ion found in space) on tissue from the heart and the BM of exposed mice. We gave adult male CBA/CaJ mice a whole-body exposure to a total dose of 0, 0.1, 0.25, or 0.5 Gy of 300 MeV/nucleon (n) ²⁸Si ions, using a fractionated schedule (two exposures, 15 days apart that totaled each selected dose). The heart and BM were collected from 5 mice per treatment group at various times up to 6 months post-irradiation. In each mouse, we obtained tissue lysates from the heart and from the total population of BM cells for measuring the levels of cleaved poly (ADP-ribose) polymerase (cleaved PARP, a marker of apoptotic cell death) and the levels of activated nuclear factor-kappa B (NF-κB) and selected NF-κB-regulated cytokines known to be involved in inflammatory responses. Our data showed that, up to 6 months post-irradiation, the levels of apoptotic cell death and inflammatory responses in tissues from the heart and BM collected from exposed mice were statistically higher than those in sham controls. Hence, these findings are suggestive of chronic apoptotic cell death and inflammation in both tissues after exposure to ²⁸Si ions. In summary, our data are indicative of a possible association between exposure to ²⁸Si ions during space flight and long-term health risk.

It has been well established that the bone marrow (BM) is a radiosensitive tissue, but the radiosensitivity of the heart is poorly understood. In this study, we investigated the comparative effects of Silicon (Si) ions (one type of heavy ion found in space) on tissue from the heart and the BM of exposed mice. We gave adult male CBA/CaJ mice a whole-body exposure to a total dose of 0, 0.1, 0.25, or 0.5 Gy of 300 MeV/nucleon (n) Si ions, using a fractionated schedule (two exposures, 15 days apart that totaled each selected dose). The heart and BM were collected from 5 mice per treatment group at various times up to 6 months post-irradiation. In each mouse, we obtained tissue lysates from the heart and from the total population of BM cells for measuring the levels of cleaved poly (ADP-ribose) polymerase (cleaved PARP, a marker of apoptotic cell death) and the levels of activated nuclear factor-kappa B (NF-κB) and selected NF-κB-regulated cytokines known to be involved in inflammatory responses. Our data showed that, up to 6 months post-irradiation, the levels of apoptotic cell death and inflammatory responses in tissues from the heart and BM collected from exposed mice were statistically higher than those in sham controls. Hence, these findings are suggestive of chronic apoptotic cell death and inflammation in both tissues after exposure to Si ions. In summary, our data are indicative of a possible association between exposure to Si ions during space flight and long-term health risk. [ABSTRACT FROM AUTHOR]

Abstract: Little is known about in vivo cytogenetic effects of protons delivered at the dose and dose rates encountered in space. We determined the effects of 100MeV protons, one of the most abundant type of protons produced during solar particle events (SPE), on the induction of chromosome aberrations (CAs) in bone marrow (BM) cells collected at early (3 and 24h) and late (6 months) time-points from groups of BALB/cJ mice (a known radiosensitive strain) exposed whole-body to 0 (sham-controls), 0.5, or 1.0Gy of 100MeV protons, delivered at 0.5 or 1.0cGy/min. These doses and dose-rates are comparable to those produced during SPE events. Additionally, groups of mice were exposed to 0 or 1Gy of 137Cs γ rays (delivered at 1cGy/min) as a reference radiation. The kinetics of formation/reduction of gamma-histone 2-AX (γH2AX) were determined in BM cells collected at 1.5, 3, and 24h post-irradiation to assess the early-response. There were five mice per treatment-group per harvest-time. Our data indicated that the kinetics of γH2AX formation/reduction differed, depending on the dose and dose rate of protons. Highly significant numbers of abnormal cells and chromatid breaks (p <0.01), related to those in sham-control groups, were detected in BM cells collected at each time-point, regardless of dose or dose-rate. The finding of significant increases in the frequencies of delayed non-clonal and clonal CAs in BM cells collected at a late time-point from exposed mice suggested that 0.5 or 1Gy of 100MeV protons is capable of inducing genomic instability in BM cells. However, the extent of effects induced by these two low dose rates was comparable. Further, the results showed that the in vivo cytogenetic effects induced by 1Gy of 100MeV protons or 137Cs γ rays (delivered at 1cGy/min) were similar. [Copyright &y& Elsevier]

Abstract: In this study, we examined the induction of chromosomal damage at day 7 following whole-body exposure of male CBA/CaJ mice to different doses of 1GeV/amu 56Fe ions (0, 0.1, 0.5, and 1.0Gy) or 137Cs γ rays as the reference radiation (0, 0.5, 1.0, and 3.0Gy, using a GammaCell40). Two cytogenetic assays were used to evaluate dose–response relationships for the induction of chromosomal damage. These include: (1) the whole-genome multi-color fluorescence in situ hybridization (mFISH) technique to examine chromosomal damage in metaphases prepared from bone marrow (BM) cells and (2) the mouse in vivo micronucleus (MN) assay to evaluate chromosomal damage (induced in the bone marrow) in blood erythrocytes. By means of the mFISH method, we detected all types of aberrations from mice exposed to either 56Fe ions or 137Cs γ rays. These were translocations (Robertsonian, reciprocal and incomplete one-way types), dicentrics and breaks (both chromatid- and chromosome-types). Each type of radiation-induced significant dose-dependent increases (ANOVA, p <0.01) in the frequencies of chromosomal damage (including the numbers of abnormal cells). Our data indicated that the 56Fe ions were more effective (per unit dose) than 137Cs γ rays in inducing damage: about four times for abnormal cells or breaks (both chromatid- and chromosome-types), and 1.6 times for exchanges (all types). Complex chromosome rearrangements were also found in BM cells of mice exposed to 1.0Gy of 56Fe ions or 3.0Gy of 137Cs γ rays, but their frequencies were low. Moreover, the frequencies of complex exchanges found at day 7 after exposure of mice to 1.0Gy of 56Fe ions or 3.0Gy of 137Cs γ rays were similar. By means of the blood MN assay, we detected dose-dependent increases in the frequencies of MN in normochromatic erythrocytes (NCE or mature red blood cells) at day 7 following in vivo exposure to 56Fe ions or 137Cs γ rays. In contrast, only a slight increase in the frequency of MN in polychromatic erythrocytes (PCE or immature red blood cells) was detected at day 7 in blood samples of mice exposed to 56Fe ions, but not 137Cs γ rays. The MN–NCE data showed that 56Fe ions were approximately four times more efficient in inducing chromosomal damage than 137Cs γ rays. The results demonstrated the sensitivity of the mouse in vivo MN assay in detecting chromosomal damage that was induced in the bone marrow of mice exposed in vivo to varying doses of 56Fe ions, when appropriate cell types were used for the analysis at a specific time post-irradiation. However, the MN assay is incapable of detecting stable-type chromosomal damage (e.g., translocation) making the MN assay less informative than the mFISH method. [Copyright &y& Elsevier]