References of "International Journal of Radiation Biology"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailProteomic and genomic modulations induced by gamma-irradiation of human blood lymphocytes.
Turtoi, Andrei ULg; Sharan, Rajesh; Srivastava, Alok et al

in International Journal of Radiation Biology (2010), 86(10), 888-904

PURPOSE: Quantitative evaluation of early response proteins (ERPRO) and early response genes (ERG) following γ-irradiation of human lymphocytes; identification of specific proteins and genes as candidate ... [more ▼]

PURPOSE: Quantitative evaluation of early response proteins (ERPRO) and early response genes (ERG) following γ-irradiation of human lymphocytes; identification of specific proteins and genes as candidate biomarkers for the development of a novel biodosimeter. MATERIALS AND METHODS: Human peripheral blood lymphocytes were exposed to clinically relevant doses (1, 2 and 4 Gy) of γ-radiation ex-vivo. Analyses of protein and gene expression modulation were conducted 2 h post-irradiation. Global modulations were monitored using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and DNA microarray analyses of the samples originating from one human donor. On the proteome level, both phosphorylated and non-phosphorylated proteins were considered. Proteins and genes of specific interest were further targeted using Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) techniques, employing samples from several human donors (n=3). RESULTS: A set of ERPRO and ERG showing significant alterations 2 h post-γ-irradiation have been identified in human lymphocytes. The most radiation responsive genes and proteins indicated alterations of cellular structure (ß-actin, talin-1 [TLN1], talin-2, zyxin-2), immune and defence reactions (major histocompatibility complex binding protein-2 [MBP2], interleukin-17E and interferon-γ), cell cycle control (cyclin-dependent kinase inhibitor-1A [CDKN1A], mouse double minute-2, annexin-A6 [ANXA6], growth arrest and DNA-damage-inducible protein-α [GADD45A], proliferating cell nuclear antigen [PCNA], dual specificity phosphatase-2 and 8 [DUSP8]) as well as detoxification processes (peroxin-1) and apoptosis (B-cell lymphoma-2 binding component-3 [BBC3]). SUMMARY: The estimations of protein concentration modulation of TLN1 and CDKN1A, phosphorylation status of ANXA6 (dose range 0-2 Gy) and MBP2 as well as the alterations in the level of gene expressions of BBC3, DUSP8, GADD45A and PCNA appears to be of potential value for future biodosimetric applications. [less ▲]

Detailed reference viewed: 31 (3 ULg)
Full Text
Peer Reviewed
See detailEffect of 211At alpha-particle irradiation on expression of selected radiation responsive genes in human lymphocytes
Turtoi, Andrei ULg; Schneeweiss, Frank H.A.

in International Journal of Radiation Biology (2009), 85(5), 403-12

Detailed reference viewed: 19 (8 ULg)
Full Text
Peer Reviewed
See detailEarly gene expression in human lymphocytes after gamma-irradiation-a genetic pattern with potential for biodosimetry.
Turtoi, Andrei ULg; Brown, Ian; Oskamp, Dominik et al

in International Journal of Radiation Biology (2008), 84(5), 375-87

PURPOSE: Identification of early radiation response genes (ERG) in human lymphocytes after gamma-irradiation by using the whole-human-genome DNA-microarrays and the evaluation of their possible role in ... [more ▼]

PURPOSE: Identification of early radiation response genes (ERG) in human lymphocytes after gamma-irradiation by using the whole-human-genome DNA-microarrays and the evaluation of their possible role in rapid radiation biodosimetry by applying real-time quantitative polymerase chain reaction (RT-qPCR) methodology for validation in a small group of human individuals. MATERIALS AND METHODS: Whole blood from a healthy human donor was exposed at 37 degrees C to 137Cs gamma-radiations (absorbed dose: 1-4 Gy). Fifteen minutes following irradiation the lymphocytes were isolated from the blood (for 2 h at 20 degrees C) and their gene expression was investigated using the DNA-microarrays. Subsequently, 14 genes were selected and validated using the TaqMan probes based upon the RT-qPCR assay within a group of 6 human donors. RESULTS: A dose-related relative change in quantitative gene expression using the DNA-microarray assay was demonstrated in 24 of 102 genes. Up-regulation of expression was observed in 15 genes: CD69 (CD69 molecule), CDKN1A (cyclin-dependent kinase inhibitor 1A), EGR1 (early growth response 1), EGR4 (early growth response 4), FLJ35725 (chromosome 4 ORF 23), hCG2041177 (hCG - human Celera Genome), hCG1643466.2, IFN-gamma (interferon-gamma), ISG20L (interferon stimulated exonuclease gene 20 kDa - like 1), c-JUN (jun oncogene), MDM2 (mouse double minute 2), MUC5B (mucine), PLK2 (polo-like kinase 2), RND1 (rho-family GTPase 1) and TNFSF9 (tumour necrosis factor superfamily member 9). Down-regulation of expression was found in the remaining nine genes: GRIK3 (glutamate receptor ionotropic kainate 3), hCG1985174, hCG1998530, hCG2038519, OCLN (occludin), RPL10A (ribosomal protein L10a), SERHL2 (serine hydrolase-like 2), SGK3 (serum/glucocorticoid regulated kinase 3) and STARD13 (START domain containing 13). CONCLUSION: A significant correlation between absorbed radiation dose and change in relative gene expression was particularly evident for EGR1, EGR4, IFN-gamma, c-JUN and TNFSF9 (p < or = 0.05). Results warrant the further investigation of these ERG as potential biodosimetric markers. [less ▲]

Detailed reference viewed: 42 (5 ULg)
Full Text
Peer Reviewed
See detailNew rationales for using TGFbeta inhibitors in radiotherapy.
Andarawewa, Kumari L.; Paupert, Jenny ULg; Pal, Anupama et al

in International journal of radiation biology (2007), 83(11-12), 803-11

PURPOSE: The first reports that ionizing radiation (IR) induces rapid and persistent activation of transforming growth factor beta1 (TGFbeta) were nearly two decades ago. Subsequent studies have shown ... [more ▼]

PURPOSE: The first reports that ionizing radiation (IR) induces rapid and persistent activation of transforming growth factor beta1 (TGFbeta) were nearly two decades ago. Subsequent studies have shown that TGFbeta is a major mediator of cellular and tissue responses to IR and have revealed novel facets of its complex biology. RESULTS: We and others have recently shown that inhibition of production or signaling of TGFbeta in epithelial cells modulates radiosensitivity and impedes activation of the DNA damage response program. The primary transducer of cellular response to DNA damage caused by ionizing radiation is the nuclear protein kinase ataxia telangiectasia mutated, whose activity is severely compromised when TGFbeta is inhibited. Thus, in conjunction, with its well-recognized contribution to normal tissue fibrosis, the role of TGFbeta in the genotoxic stress program provides a previously unsuspected avenue to modulate radiotherapy. CONCLUSIONS: We hypothesize that identification of the circumstances and tumors in which TGFbeta manipulation enhances tumor cell radiosensitivity, while protecting normal tissues, could significantly increase therapeutic index. [less ▲]

Detailed reference viewed: 10 (0 ULg)
Full Text
Peer Reviewed
See detailMarrow stromal cell recovery after radiation-induced aplasia in mice
Almohamad, Khaled; Thiry, Albert ULg; Hubin, Frédérique et al

in International Journal of Radiation Biology (2003), 79(4), 259-67

Detailed reference viewed: 17 (2 ULg)
Peer Reviewed
See detailTranslocation Frequencies Measured in Patients One Year after Radioactive Iodine Therapy for Thyrotoxicosis
Lambert, Vincent ULg; Thierens, H.; Monsieurs, M. et al

in International Journal of Radiation Biology (2001), 77(6), 679-85

PURPOSE: To investigate the incidence of translocations induced by iodine-131 therapy in thyrotoxicosis patients 1 year after the administration of the radiolabelled compound. MATERIALS AND METHODS ... [more ▼]

PURPOSE: To investigate the incidence of translocations induced by iodine-131 therapy in thyrotoxicosis patients 1 year after the administration of the radiolabelled compound. MATERIALS AND METHODS: Tricolour FISH with whole-chromosome-specific probes for chromosomes 2, 4 and 8 was used for scoring translocations. From the genomic translocation frequencies, derived using the Lucas formula, equivalent whole-body doses were calculated, based on the in vitro (60)Co gamma-ray dose-response curve. RESULTS: A total of 101 translocations were observed in 4864 metaphases, 63% being of the two-way type. In the control group used for obtaining dose-response data, nine translocations were observed in 5278 metaphases, 55% being two-way translocations. No correlation was found between the observed frequency of translocations and administered radioactivity. Using the in vitro dose-response, an estimated average dose for the group of nine patients of 0.79 +/- 0.22Gy was obtained. Compared with frequencies following the assumption that the involvement of a particular chromosome in a two-break exchange-type aberration is proportional to its DNA content, chromosome 4 was more frequently involved and chromosomes 2 and 8 less frequently involved in chromosomal rearrangements. CONCLUSION: This study shows that (131)I therapy for thyrotoxicosis patients induced translocations, especially in chromosome 4, which could be detected 1 year after the administration of the radiolabelled compound. [less ▲]

Detailed reference viewed: 10 (1 ULg)
Peer Reviewed
See detailCellular Events in Radiation-Induced Lymphomagenesis
Boniver, Jacques ULg; Humblet, Chantal ULg; Rongy, A. M. et al

in International Journal of Radiation Biology (1990), 57(4), 693-8

Fractionated whole-body irradiation induces thymic lymphomas in most of treated C57Bl/Ka mice. The cellular events occurring during the latency period consist of the emergence of preleukaemic cells and of ... [more ▼]

Fractionated whole-body irradiation induces thymic lymphomas in most of treated C57Bl/Ka mice. The cellular events occurring during the latency period consist of the emergence of preleukaemic cells and of marked alterations to the T-cell lineage and the microenvironment within the thymus. The proportions of the various thymocyte subsets are modified, suggesting a blockage in the normal differentiation process. Thymic epithelial cells are functionally modified, leading to decreased interactions with immature thymocytes. Interestingly, bone marrow grafting early after irradiation, which inhibits the development of lymphomas, induces the disappearance of preleukaemic cells from the thymus, whereas thymocyte subpopulations and thymic epithelium are restored. Interferon gamma and tumor necrosis factor alpha also prevent the onset of lymphomas. Studies on the effect of bone marrow transplantation and cytokine inoculation in split-dose irradiated mice should allow characterization of the factors that modulate the progression of preleukaemic cells towards the neoplastic state. [less ▲]

Detailed reference viewed: 15 (3 ULg)