The effect of cold after whole-body irradiation of the mouse

Journal of Thermal Biology, 2004

Mild whole body hyperthermia (WBH) treatment when given prior to radiation exposure is known to protect mice against radiation-induced hemopoietic death. This radioprotective effect seems to be mediated through WBH-induced cytokines and growth factors. Exposure to total body irradiation (TBI) also induces cell death by apoptosis in animal cells. The present studies were therefore carried out to investigate whether WBH pretreatment could protect mice against radiation-induced apoptotic death. The extent of apoptosis in bone marrow cells derived from mice at different time intervals after WBH, TBI and whole body hyperthermia treatment given 20 h prior to total body irradiation (WBH+TBI) treatments was studied by three independent methods namely DNA ladder assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay and caspase-3 assay. The studies have revealed that the mild WBH treatment (39 C, 1 h) when given 20 h prior to TBI (8 Gy) results in reduction in TBI-induced apoptosis. The results imply that WBH-induced impairment of apoptosis may have some role in WBHinduced radioprotection in Swiss mice. r

Acta Oncologica, 2014

The aim of this work was to investigate the impact of intercellular contact during radiation exposure on cell survival in regions of reduced dose. Methods. The PC3 human prostate adenocarcinoma cell line was irradiated using a 6 MV x-ray beam to assess clonogenic cell deaths with the specifi c aim to investigate cell survival in a dose cold spot. Radiation-induced cell survival in a 20% lower dose region, compared to that of cells receiving 100% of the prescribed dose (2 Gy), was assessed for experimental set-ups when under-irradiated cells were either in direct contact with cells receiving 2 Gy or irradiated separately. In addition, the results were compared against non-irradiated controls. Results. A signifi cant (p Ͻ 0.001) decrease in cell survival was found when cells, collocated in the same fl ask, received either 100% or 80% of the prescribed dose (the dose distribution contained a cold spot of 20% lower dose) compared to non-irradiated cells. However, in the experiment in which the entire fl ask was exposed to only 80% of the prescribed dose, the mean difference in cell survival compared to non-irradiated control was not signifi cant (p Ͼ 0.05). This was contrary to a signifi cant decrease (p Ͻ 0.001) in survival of cells receiving 100% of the prescribed dose versus the control. Additionally, signifi cant reduction (p Ͻ 0.05) in cell survival was observed for cells which were under-irradiated by 20% but collocated in the same fl ask with cells receiving 100% dose compared to cells where the entire fl ask was irradiated with 80% of the prescribed dose. Conclusion. For the given cell line, under existing growing and treatment conditions, the cell survival in the dose cold spot region was signifi cantly lower when under-irradiated cells were in contact with the cells receiving 100% of the prescribed dose compared to survival of cells under-irradiated by the same amount of radiation but treated separately to cells receiving 100% dose.

Acta veterinaria, 2005

Phenotypic changes of thymic epithelial cells (TEC) were studied in male Wistar rats subjected to radioprotector WR-638 (358 mg/kg b.w. ip) and/or whole body X-ray irradiation (3.5 Gy) 15 days after its application. Phenotypic changes were identified in situ on cryostat thymic sections using immunohistochemical staining by a panel of monoclonal anti-cytokeratin antibodies. It was shown that WR-638 significantly reduced changes in the structure of the thymus caused by X-ray irradiation. In the primary involution phase some phenotypic characteristic changes of TEC can be explained mostly by lymphoid destruction, although factors directly connected to the protector can not be excluded. However, in the primary regenerative phase WR-638 caused prominent changes of antigen expression on subcapsular and medullary TEC in irradiated rats. Therefore, WR-638 not only protects thymocytes, but also causes alterations of phenotypic characteristics of TEC which may contribute to its beneficial radioprotective effect on the irradiated rat thymus.

The Journal of Immunology, 2017

Total body irradiation (TBI) damages hematopoietic cells in the bone marrow and thymus; however, the long-term effects of irradiation with aging remain unclear. In this study, we found that the impact of radiation on thymopoiesis in mice varied by sex and dose but, overall, thymopoiesis remained suppressed for ‡12 mo after a single exposure. Male and female mice showed a long-term dose-dependent reduction in thymic cKit + lymphoid progenitors that was maintained throughout life. Damage to hematopoietic stem cells (HSCs) in the bone marrow was dose dependent, with as little as 0.5 Gy causing a significant long-term reduction. In addition, the potential for T lineage commitment was radiation sensitive with aging. Overall, the impact of irradiation on the hematopoietic lineage was more severe in females. In contrast, the rate of decline in thymic epithelial cell numbers with age was radiation-sensitive only in males, and other characteristics including Ccl25 transcription were unaffected. Taken together, these data suggest that long-term suppression of thymopoiesis after sublethal irradiation was primarily due to fewer progenitors in the BM combined with reduced potential for T lineage commitment. A single irradiation dose also caused synchronization of thymopoiesis, with a periodic thymocyte differentiation profile persisting for at least 12 mo postirradiation. This study suggests that the number and capability of HSCs for T cell production can be dramatically and permanently damaged after a single relatively low TBI dose, accelerating aging-associated thymic involution. Our findings may impact evaluation and therapeutic intervention of human TBI events.

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 1998

To investigate the effect of ex vivo hyperthermia HT and Cs-irradiation on micronucleus MN production in Ž. cytokinesis-blocked lymphocytes, we obtained the peripheral blood samples from the same cancer patients n s 6 before Ž. and during fractionated partial-body radiotherapy xRT. The whole blood cultures were heated at 43.58C for 60 min, 137 Ž. followed by Cs irradiation 0-4 Gy. The control cultures from the same patients were incubated at 378C after being exposed to radiation. The lymphocytes were then stimulated with PHA. Cytochalasin B was applied at 44 h, and lymphocytes were harvested at 72 h. MN frequency was determined on Giemsa-stained slides. We found that in patients Ž. Ž. before xRT, HT 43.58C significantly increased the MN yield mean " SEM in unirradiated lymphocytes from 15.6 " 2.8 Ž. Ž. 378C to 39.7 " 10.9. Further, in patients either before or during xRT, when the lymphocytes were treated with HT 43.58C Ž. and combined with ex vivo irradiation, the MN yield Y could be estimated by a linear equation Y s C q a D. Our findings indicate that as measured by the MN production in cytokinesis-blocked lymphocytes, HT alone at 43.58C induced DNA damage. Moreover, it enhanced the radiation-induced cytogenetic damage. Therefore, the application of HT may impair the T-cell function in cancer patients who are receiving radiotherapy.

Journal of Thermal Biology, 2002

Studies were carried out to gain an insight into the mechanisms underlying WBH induced radioprotection. The plasma levels of IL-1a, IL-6, TNF-a and GM-CSF, were elevated in WBH treated mice between 2 and 6 h after treatment. The total nucleated cell count of hemopoietic tissues such as spleen, thymus, bone marrow and peripheral blood showed drastic reduction without recovery until death in mice treated with TBI. However, the nucleated cell count in the above tissues showed significant recovery after initial drop in WBH and WBH+TBI treated groups and reached to a normal level by day 7 and day 28, respectively. The total WBC and RBC count in peripheral blood recovered to a control level by day 28 after treatment. Significant number of endogenous spleen colonies were detected, 14 days after TBI in WBH pre-treated mice whereas no such spleen colonies could be detected in TBI treated group. The transplantation of bone marrow derived from control, WBH, TBI and WBH+TBI treated groups of mice to lethally irradiated mice (8 Gy) showed formation of spleen colonies only in mice which received bone marrow from control, WBH and WBH+TBI treated groups. Transplantation of the bone marrow from these groups of mice resulted in prolonged survival of lethally irradiated mice as compared to mice receiving bone marrow from TBI treated mice. These results seem to suggest that WBH induced radioprotection of mice could be due to immunomodulation manifested through induction of cytokines responsible for protection and proliferative response, leading to accelerated recovery from hemopoietic damage-a major cause of radiation induced death. #

Proceedings of the National Academy of Sciences, 1989

After sublethal (6 Gy) whole-body irradiation, the C57BL/Ba (Thy-1.1) murine thymus regenerated in two waves, on days 3-10 and 25-32, separated by a severe relapse. The second phase of depletion-reconstitution reproduced the first one, in a less synchronous manner. The depletion affected all cell subsets, but CD4+ CD8- cells decreased later than immature cells. Cell proliferation, measured by BrdUrd incorporation, started on day 3 after irradiation and concerned CD4- CD8-, CD4- CD8+, and CD4+ CD8+ cells, sequentially. CD4+ CD8- cells never represented a significant percentage of cycling cells. When irradiation was immediately followed by an intrathymic injection of 10(5) C57BL/Ka (Thy-1.2) bone marrow cells, the relapse in thymus reconstitution was no longer observed. Detected with anti-Thy-1.2 antibodies, donor cells started cycling on day 14 and showed only one wave of proliferation. In these chimeras, recipient thymocytes behave exactly like thymocytes of solely irradiated mice. ...

In vivo (Athens, Greece)

The major aim of this study was to quantify long-term changes in bone marrow-derived cell populations after exposure to radiations of differing quality. Mice were whole-body irradiated to 2 Gy gamma, proton, carbon or iron radiation, and euthanized approximately 110 days later for immunocyte phenotyping. Splenic lymphocytes and mono/macrophages increased after gamma-rays when compared to 0 Gy and one or more of the other groups. There were high T cells (carbon vs. 0 Gy), high B cells (gamma-rays vs. 0 Gy), and low natural killer (NK) cells (proton and carbon vs. 0 Gy). All radiations, except gamma-rays, increased CD62L+ memory T cell counts, whereas CD62L+ B cells increased only after gamma-rays. There were significant aberrations in many immune parameters nearly 4 months after exposure to various forms of radiation. This suggests radiation exposure can have long-term health consequences.

Mutation research, 1991

To evaluate the application of the cytokinesis-block (CB) micronucleus (MN) assay as a biological dosimeter following in vivo exposure to ionising radiation we determined the micronucleus frequency in spleen and peripheral blood lymphocytes of the mouse, serially, for 14 days following acute whole-body irradiation. The baseline MN frequency of spleen lymphocytes (7.86 +/- 0.68, mean +/- 1 SD) was significantly (p less than 0.001) elevated when compared to that for peripheral blood lymphocytes (4.10 +/- 0.53). Immediately after irradiation there was a substantial dose-related increase in MN, but the MN frequencies in spleen lymphocytes (120.2 +/- 9.4 for 1 Gy; 409.5 +/- 38.4 for 2 Gy) were significantly (p less than 0.009) elevated compared to those in peripheral blood lymphocytes (78.0 +/- 7.0 for 1 Gy; 200.2 +/- 10.9 for 2 Gy). During the 14 days after irradiation, the MN frequency in spleen lymphocytes declined gradually to approximately half of the value observed immediately afte...

Developmental Immunology, 1995

Sublethal irradiation of the murine thymus has been a useful tool for depleting the thymus of dividing immature thymocyte subsets, to sequence thymocyte differentiation events occurring from radiation-resistant precursors. This massive reduction in thymocytes also represents a model in which the bidirectional interplay between the thymic stromal cells and lymphocytes can be investigated. The purpose of this study was thus twofold: to precisely map the initiation of thymopoiesis as a prelude to assessing the effects of injected mAb to novel thymic antigens; and to use a panel of mAbs to determine the alterations in the thymic stroma during the T-cell depletion and reconstitution phases. The striking finding from this study was that following T-cell depletion, there was a marked upregulation of specific stromal antigens, which retracted with the reappearance of T cells. Thus, following sublethal irradiation, there are modifications in the thymic microenvironment that may be necessary ...