Repopulation in irradiated pig skin: late versus early effects

International Nuclear Information System (INIS)

Redpath, J.L.; Peel, D.M.; Dodd, P.; Simmonds, R.H.; Hopewell, J.W.

1985-01-01

In the first 16 weeks after irradiation, two distinct waves of reaction can be observed in pig skin, the first wave (3-9 weeks) represents the expression of damage to the epithelium while the second is indicative of primary damage to the dermis, mediated through vascular injury. Comparison of single doses with two equal doses separated by 28 days produced a D 2 -D 1 value of 14.0 Gy at the doses which produced moist desquamation in 50% of fields (ED 50 ) after strontium-90 irradiation. After X-irradiation, comparison of ED 50 doses for the later dermal reaction suggested a D 2 -D 1 value of 4.2 Gy. These values of D 2 -D 1 for epithelial and dermal reactions in pig skin were compared with earlier data from this laboratory for similar split-dose experiments with a one-day interval. Such a comparison allowed for the estimation of the component of recovery in the present 28-day interval experiments due to repopulation. This component was found to be 6.5 Gy for the early epithelial damage, but was zero for the later dermal damage. (Auth.)

The increased susceptibility of hematopoietic stem cells to Friend leukemia virus in the repopulating period

International Nuclear Information System (INIS)

Hirashima, Kunitake; Kumatori, Toshiyuki

1977-01-01

The present study considers two fundamental problems of leukemia and stem cells: (1) whether the target cells for malignant transformation of Friend leukemia virus (FV) are the pluripotential stem cells; (2) whether the susceptibility of the target cell is changeable depending on the proliferating state of the cell. In the experiments, inbred 8- to 12-week-old C3H/He and BC3Fl hybrid mice were used. As target cells for FV, two candidate cell populations should be considered. These are the pluripotential stem cells expressed as CFUs and the committed stem cells expressed as erythropoietin-responsive cells (ERC). According to our preliminary experiments on the recovery patterns of CFUs or ERC, after a single 150 rads X-irradiation (X) or administration of 215 mg/kg of cyclophosphamide (CY), it was clear that the repopulation of CFUs was quite different from that of ERC. The target cells for FV-induced transformation are the stem cells expressed as CFUs and the susceptibility of these increases under conditions of active repopulation after X-irradiation and cyclophosphamide administration. After the irradiation especially, this effect is dose-dependent for doses over 25 rads at 2 weeks after irradiation. (Auth.)

Repair, redistribution and repopulation in V79 spheroids during multifraction irradiation

International Nuclear Information System (INIS)

Brown, R.C.; Durand, R.E.

1994-01-01

We used cells growing as multicell spheroids to determine whether the initial radiation response would be predictive for multifraction exposures, or whether other factors including repopulation rate should be considered. Potential problems of hypoxia and reoxygenation were avoided by using small spheroids which had not yet developed radiobiologically hypoxic regions. Repair and redistribution dominated the responses in the first two or three exposures, with repopulation playing a minor role. As the fractionation schedule was extended, however, repopulation between fractions largely determined the number of viable cells per spheroid. We conclude that the radiation response of cells from untreated spheroids provides a general indication of net sensitivity, but that repair and redistribution produces considerable variation in radiosensitivity throughout a fractionation protocol. Ultimately, repopulation effects may dominate the multifraction response. (Author)

Repopulation of FaDu human squamous cell carcinoma during fractionated radiotherapy correlates with reoxygenation

International Nuclear Information System (INIS)

Petersen, Cordula; Zips, Daniel; Krause, Mechthild; Schoene, Kerstin; Eicheler, Wolfgang; Hoinkis, Cordelia; Thames, Howard D.; Baumann, Michael

2001-01-01

Purpose: FaDu human squamous cell carcinoma (FaDu-hSCC) showed a clear-cut time factor during fractionated radiotherapy (RT) under ambient blood flow. It remained unclear whether this is caused solely by proliferation or if radioresistance resulting from increasing hypoxia contributed to this phenomenon. To address this question, repopulation of clonogenic FaDu cells during fractionated RT under clamp hypoxia was determined by local tumor control assays, and compared to the results after irradiation with the same regimen under ambient blood flow. Methods and Materials: FaDu-hSCC was transplanted into the right hind leg of NMRI nu/nu mice. In the first set of experiments, irradiation was performed under clamp hypoxia. After increasing numbers of 3 Gy fractions (time intervals 24 h or 48 h), graded top-up doses were given to determine the TCD 50 (dose required to control 50% of the tumors). In the second set of experiments, all 3 Gy fractions were applied under ambient conditions, but as in the previous experiments the graded top-up doses were given under clamp hypoxia. A total of 26 TCD 50 assays were performed and analyzed using maximum likelihood techniques. Results: With increasing numbers of daily fractions, the top-up TCD 50 under clamp hypoxia decreased from 39.4 Gy [95% CI 36, 42] after single dose to 19.8 Gy [15, 24] after 18 fractions in 18 days and to 37.8 Gy [31, 44] after 18 fractions in 36 days. The results were consistent with biphasic repopulation, with a switch to rapid repopulation after about 22 days [13, 30]. The clonogen doubling time (T clon ) decreased from 9.8 days [0, 21] in the beginning of RT to 3.4 days after 22 days. Under ambient blood flow the top-up TCD 50 decreased from 37.6 Gy [34, 40] after single dose irradiation to 0 Gy [0, 1] after 18 fractions in 18 days and 22.4 Gy [18, 27] after 18 fractions in 36 days. Similar to results from irradiations under clamp hypoxia, the ambient data were consistent with a biphasic course of clonogen

Modelling of post-irradiation accelerated repopulation in squamous cell carcinomas

International Nuclear Information System (INIS)

Marcu, L; Doorn, T van; Olver, I

2004-01-01

The mechanisms postulated to be responsible for the accelerated repopulation of squamous cell carcinomas during radiotherapy are the loss of asymmetry of stem cell division, acceleration of stem cell division, abortive division and/or recruitment of the non-cycling cell with proliferative capacity. Although accelerated repopulation was observed with recruitment and accelerated cell cycles, it was not sufficient to cause an observable change to the survival curve. However, modelling the loss of asymmetry in stem cell division has reshaped the curve with a 'growth' shoulder. Cell recruitment was not found to be a major contributor to accelerated tumour repopulation. A more significant contribution was provided through the multiplication of surviving tumour stem cells during radiotherapy, by reducing their cell cycle time, and due to loss of asymmetry of stem cell division

Acute skin reaction after fractionated irradiation

International Nuclear Information System (INIS)

Kozubek, S.

1983-01-01

Experimental data on acute mouse and pig skin reaction after fractionated γ or X irradiation have been analysed in terms of a new cell tissue kinetic model. The exponential-quadratic and generalized Huggett formulae have been used for cell lethality description. Fairly better results could be demonstrated with generalized Huggett formula. The speed of repopulation has been determined for fractionated regimes as well as for some irregular schedules. The repopulation is slower in the case of fractionated treatment. On considering the normal cell loss factor in the tissue, minimum cell cycle time has been calculated. Its value differs for various strains (Tsub(d)=28.8 hours for SAS/TO mice and Tsub(d) < or approximately 17 hours for WHT/Ht mice) and does not differ for plucked skin. The repopulation has been shown to follow exponential dependence after some latent period. Other factors influencing the effectiveness of radiation treatment (the length of the latent period or the changes of the survival curve during fractionated irradiation) have been considered, too

Repopulation capacity during fractionated irradiation of squamous cell carcinomas and glioblastomas in vitro

Energy Technology Data Exchange (ETDEWEB)

Budach, Wilfried; Gioioso, Danielle; Taghian, Alphonse; Stuschke, Martin; Suit, Herman D

1997-10-01

Purpose: Determination of clonogenic cell proliferation of three highly malignant squamous cell carcinomas (SCC) and two glioblastoma cell lines during a 20-day course of fractionated irradiation under in vitro conditions. Methods and Materials: Tumor cells in exponential growth phase were plated in 24-well plastic flasks and irradiated 24 h after plating with 250 kV x-rays at room temperature. Six fractions with single doses between 0.6 and 9 Gy were administered in 1.67, 5, 10, 15, and 20 days. Colony growth was monitored for at least 60 days after completion of irradiation. Wells with confluent colonies were considered as 'recurrences' and wells without colonies as 'controlled'. The dose required to control 50% of irradiated wells (WCD{sub 50}) was estimated by a logistic regression for the different overall treatment times. The effective doubling time of clonogenic cells (T{sub eff}) was determined by a direct fit using the maximum likelihood method. Results: The increase of WCD{sub 50} within 18.3 days was highly significant for all tumor cell lines accounting for 7.9 and 12.0 Gy in the two glioblastoma cell lines and for 12.7, 14.0, and 21.7 Gy in the three SCC cell lines. The corresponding T{sub eff}s were 4.4 and 2.0 days for glioblastoma cell lines and 2.4, 4.2, and 1.8 days for SCC cell lines. Population doubling times (PDT) of untreated tumor cells ranged from 1.0 to 1.9 days, showing no correlation with T{sub eff}s. T{sub eff} was significantly longer than PDT in three of five tumor cell lines. No significant differences were observed comparing glioblastomas and SCC. Increase of WCD{sub 50} with time did not correlate with T{sub eff} but with T{sub eff}* InSF2 (surviving fraction at 2 Gy). Conclusion: The intrinsic ability of SCC and glioblastoma cells to repopulate during fractionated irradiation could be demonstrated. Repopulation induced dose loss per day depends on T{sub eff} and intrinsic radiation sensitivity. Proliferation during treatment was

Numbers and dispersion of repopulating hematopoietic cell clones in radiation chimeras as functions of injected cell dose

International Nuclear Information System (INIS)

Micklem, H.S.; Lennon, J.E.; Ansell, J.D.; Gray, R.A.

1987-01-01

Lethally irradiated mice were repopulated with low (10(5)), medium (10(6)) or high (10(7)) doses of congenic bone marrow cells. Marrow donors were heterozygous for the X-chromosome-encoded allozyme marker phosphoglycerate kinase (PGK-1). A second allozyme marker, phosphoglucose isomerase (GPI-1), distinguished between donor and radioresistant host cells. Use of these markers allowed the numbers and dispersion of repopulating hematopoietic clones to be estimated by binomial statistics. The number of major repopulating clones was related to the injected cell dose in a linear fashion, the inferred frequency of clonogenic cells in donor bone marrow being about 1:40,000. In high-dose recipients, the clones grew locally, with little or no dispersion between bones. Low-dose recipients, in contrast, carried widely dispersed clones; these tended to become reduced in number with increasing time after repopulation. Most of the (few) bone marrow clones present in low-dose recipients were also present in the thymus. In contrast, only about 10% of bone marrow clones in high-dose recipients were substantially represented in the thymus at any one time--about 16 clones in each lobe

Increase of survival of x-irradiated mice by postirradiation injections of a splenic extract prepared from vaccine or endotoxin-treated syngeneic animals

Energy Technology Data Exchange (ETDEWEB)

Tsuneoka, K; Takagi, Y; Shikita, M [National Inst. of Radiological Sciences, Chiba (Japan)

1977-05-01

Spleens of mice which had been treated with E. coli endotoxin or typhoid-paratyphoid vaccine were extracted with isotonic saline. The extract was filtered through an asbestos filter and chromatographed on a Sephadex G-200 column. The fraction which was excluded at around 2.5-void volume (molecular weight, about 20,000) was significantly effective in increasing survival of animals when it was repeatedly injected in mice after x irradiation (600 R). The injection caused an increase of the weight of spleen of the animals with an increased number of endogenous spleen colonies. The result suggests that the life-saving effect of the spleen extract is based on its effect of stimulating repopulation of autochthonous hematopoietic cells in the x-irradiated animals. A similar splenic extract prepared from normal mice had an ambiguous effect on the survival of x-irradiated animals.

Characterizing newly repopulated microglia in the adult mouse: impacts on animal behavior, cell morphology, and neuroinflammation.

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Monica R P Elmore

Full Text Available Microglia are the primary immune cell in the brain and are postulated to play important roles outside of immunity. Administration of the dual colony-stimulating factor 1 receptor (CSF1R/c-Kit kinase inhibitor, PLX3397, to adult mice results in the elimination of ~99% of microglia, which remain eliminated for as long as treatment continues. Upon removal of the inhibitor, microglia rapidly repopulate the entire adult brain, stemming from a central nervous system (CNS resident progenitor cell. Using this method of microglial elimination and repopulation, the role of microglia in both healthy and diseased states can be explored. Here, we examine the responsiveness of newly repopulated microglia to an inflammatory stimulus, as well as determine the impact of these cells on behavior, cognition, and neuroinflammation. Two month-old wild-type mice were placed on either control or PLX3397 diet for 21 d to eliminate microglia. PLX3397 diet was then removed in a subset of animals to allow microglia to repopulate and behavioral testing conducted beginning at 14 d repopulation. Finally, inflammatory profiling of the microglia-repopulated brain in response to lipopolysaccharide (LPS; 0.25 mg/kg or phosphate buffered saline (PBS was determined 21 d after inhibitor removal using quantitative real time polymerase chain reaction (RT-PCR, as well as detailed analyses of microglial morphologies. We find mice with repopulated microglia to perform similarly to controls by measures of behavior, cognition, and motor function. Compared to control/resident microglia, repopulated microglia had larger cell bodies and less complex branching in their processes, which resolved over time after inhibitor removal. Inflammatory profiling revealed that the mRNA gene expression of repopulated microglia was similar to normal resident microglia and that these new cells appear functional and responsive to LPS. Overall, these data demonstrate that newly repopulated microglia function

Interplay of thymus and bone marrow regeneration in x-irradiated mice

International Nuclear Information System (INIS)

Hiesche, K.-D.

1975-01-01

aim of the prepresent investigation was to study the modifying effects of bone marrow cells on regeneration, after X-irradiation, of thymus and bone marrow cell populations. Data are presented which indicate that the cellular composition of the thymus and, in particular, the frequency of the stem cells in the organ at the time of radiation exposure determines thymic regeneration for about two weeks after irradiation. After this period, regeneration depends on new precursors from the bone marrow which have previously seeded the thymus. In contrast to the thymus, cellular restoration of the bone marrow is already initially dependent on the number of protected or transplanted marrow cells. Two phases in the recovery of thymic PHA-reactivity after irradiation were observed: one initial phase which is independent on the number of the available bone marrow cells, and a subsequent phase during which PHA-reactivity is slightly increased in mice irradiated with partly protected bone marrow in comparison to in total body irradiated animals. During the entire observation period, PHA-reactivity remains at a low level not exeeding 50 % of that in untreated mice. In contrast the thymus is fully repopulated with regard to the number of nonreactive cells. Alternative pathways of thymocyte development within the thymus are discussed. Bone marrow X cells were shown to be as sensitive to in vitro treatment with a specific H-2 antiserum as were lymphocytes from normal bone marrow. This finding was teken to indicate that the X cells represent a particular lymphoid cell type. A xenogeneic rabbit-anti-mouse embryo antiserum was more toxic to pre-irradiated bone marrow, with high proportion of X cells, than to bone marrow from untreated mice, using in vitro cytotoxicity test. A possible embryonic character of the X cells is discussed. (author)

Interplay of thymus and bone marrow regeneration in x-irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Hiesche, K D

1975-01-01

The aim of the present investigation was to study the modifying effects of bone marrow cells on regeneration, after X-irradiation, of thymus and bone marrow cell populations. Data are presented which indicate that the cellular composition of the thymus and, in particular, the frequency of the stem cells in the organ at the time of radiation exposure determines thymic regeneration for about two weeks after irradiation. After this period, regeneration depends on new precursors from the bone marrow which have previously seeded the thymus. In contrast to the thymus, cellular restoration of the bone marrow is already initially dependent on the number of protected or transplanted marrow cells. Two phases in the recovery of thymic PHA-reactivity after irradiation were observed: one initial phase which is independent on the number of the available bone marrow cells, and a subsequent phase during which PHA-reactivity is slightly increased in mice irradiated with partly protected bone marrow in comparison to in total body irradiated animals. During the entire observation period, PHA-reactivity remains at a low level not exeeding 50 % of that in untreated mice. In contrast the thymus is fully repopulated with regard to the number of nonreactive cells. Alternative pathways of thymocyte development within the thymus are discussed. Bone marrow X cells were shown to be as sensitive to in vitro treatment with a specific H-2 antiserum as were lymphocytes from normal bone marrow. This finding was teken to indicate that the X cells represent a particular lymphoid cell type. A xenogeneic rabbit-anti-mouse embryo antiserum was more toxic to pre-irradiated bone marrow, with high proportion of X cells, than to bone marrow from untreated mice, using in vitro cytotoxicity test. A possible embryonic character of the X cells is discussed.

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A. [Academy of Sciences of the Czech Republic, Inst. of Biophysics, Brno (Czech Republic); Znojil, V.; Vacha, J. [Masaryk Univ., Medical Faculty, Brno (Czech Republic)

1998-03-01

The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of {sup 60}Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au) 43 refs.

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

International Nuclear Information System (INIS)

Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A.; Znojil, V.; Vacha, J.

1998-01-01

The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of 60 Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au)

Phenotypic characterization of early events of thymus repopulation in radiation bone marrow chimeras

International Nuclear Information System (INIS)

Sharrow, S.O.; Singer, A.; Hammerling, U.; Mathieson, B.J.

1983-01-01

The phenotype of murine thymocytes repopulating the thymus of radiation bone marrow chimeras shortly after irradiation and bone marrow reconstitution was analyzed by immunofluorescence and flow microfluorometry. Thymuses in these chimeras, while essentially devoid of lymphoid cells at day 7, were repopulated by days 10 to 12 after irradiation. It was found that this initial repopulation arose from a radioresistant intrathymic precursor that expanded to an almost complete complement of host-type thymocytes. However, these host-derived thymocytes were unusual in that they were relatively deficient in Lyt 1+2- and peanut agglutinin ''dull'' cells as compared with normal thymocytes. Donor bone-marrow-derived cells first appeared in the irradiated chimeric thymuses between days 12 and 15 after irradiation and bone marrow transfer. By day 19, chimeric thymuses contained more than 98% donor cells. This course was identical for three chimeric combinations, each made across different genetic barriers. In contrast to the cells that populate the fetal thymus during normal ontogeny, the first donor bone-marrow-derived cells that can be detected within the irradiated chimeric thymuses already expressed phenotypically normal adult T cell subpopulations in that they contained significant numbers both of Lyt 1+2- and of Lyt 1+2+ thymocytes. Thus, the Lyt phenotype of donor cells that initially repopulate an adult thymus after irradiation is markedly different from the Lyt phenotype of cells that initially populate the fetal thymus. The differences between adult and fetal thymic development that are observed in radiation bone marrow chimeras may be important in our understanding of T cell differentiation in these animals

Protective effects of a preparation(hemoHIM) of herb mixture on self-renewal tissues and immune system in whole body irradiated mice

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Park, Hae-Ran; Oh, Heon; Jo, Sung-Kee [Korea Atomic Energy Research Institute, Daejon (Korea, Republic of); Kim, Sung-Ho [Chonnam National Univ., Kwangju (Korea, Republic of); Yee, Sung-Tae [Sunchon National Univ., Sunchon (Korea, Republic of)

2002-07-01

A preparation (HemoHIM) of herb mixture was designed to protect the gastrointestine and hematopoietic organs and to promote recovery of the immune system against radiation damage. The mixture of 3 edible medicinal herbs (Angelica gagantis Radix, etc.) was decocted with hot water and the extract was fractionated with ethanol. The preparation HemoHIM was made up with addition of ethanol- insoluble fraction yielded from one half of the total water extract to the other half of the total water extract. In vitro, lymphocytes were protected by HemoHIM, its polysaccharide and ethanol fractions against radiation. The proliferation of lymphocytes and bone marrow cells by HemoHIM was due to its polysaccharide fraction. In mice administered with the preparation (HemoHIM) before gamma- irradiation, the jejunal crypt survival was increased and the apoptosis of crypt cells was decreased. HemoHIM administration increased the survival of bone marrow stem cells and promoted the repopulation of blood cells following irradiation. In the analysis of the repopulated lymphocyte subsets, B cells were firstly regenerated and then T cells were recovered in mice administrated with HemoHIM. The antibody production against T-dependent antigen DNP-KLH was augmented by HemoHIM in irradiated mice. These results indicated that HemoHIM, a preparation of the herb mixture, protected the stem cells of self-renewal tissues and hematopoietic organs and promoted recovery of the immune system against radiation damage. Since the preparation of herb mixture is a relatively nontoxic natural product, it might be a useful modifier for prevention and control of radiation damages.

Competitive proliferation in the hematopoietic tissues of irradiated hybrid mice engrafted with parental bone marrow and spleen

International Nuclear Information System (INIS)

Muramatsu, S.; Monnot, P.; Duplan, J.F.

1976-01-01

e kinetics of growth and differentiation of hematopoietic stem cells differ markedly according to their origin. A study of the ability of CFU from bone marrow (BM) or spleen to repopulate hemopoietic organs has been carried out in lethally irradiated mice restored with BM cells admixed with spleen cells bearing different chromosomal markers. Hemopoietic cells originating from AKR (40 acbrocentrics) and AKR/T1ALD (36 acrocentrics + 2 metacentrics) mice were engrafted into lethally irradiated (AKR x AKR/T1ALD)F1 or (C3H x AKR/T1ALD)F1 hybrid recipients. Within 10 days, the BM-derived elements outnumbered the spleen-derived population in BM and spleen. This held even when the number of injected spleen-CFU was twice that of BM-CFU. This difference of growth rate subsided within 20 days. The first cells to reappear in the thymus bore the recipient karyotype (endoregeneration); they were later replaced by BM-derived elements but spleen-derived cecells were never present in thymus in the case of competitive engraftment. In contrast, the lymph node cells bore the BM karyotype as well as the spleen karyotype. Injecting the spleen cells 3 days prior to the BM cells partially counterbalanced the overgrowth of the BM-derived elements in the BM and spleen but did not affect the thymic repopulation which remained strictly derived from BM-CFU. When mice were injected only with BM-CFU, or only with spleen-CFU, BM-derived cells were found in the thymus as early as 10-12 days after engraftment, whereas the spleen-derived cells did not appear in the thymus until days 18-20. (author)

The repopulation of lymph nodes of dogs after 1200 R whole-body x-irradiation and intravenous administration of mononuclear blood leukocytes.

Science.gov (United States)

Nelson, B; Calvo, W; Fliedner, T M; Herbst, E; Bruch, C; Schnappauf, H P; Flad, H D

1976-08-01

Fresh and cryopreserved autologous or allogeneic mononuclear blood cells (MBCs) intravenously injected in 1200 R total-body x-irradiated dogs repopulated lymph nodes within 10 days after tranfusion. Several parameters of the lymphopoietic regeneration were correlated with the number of cells transfused and with the number of colony-forming units contained in the cell suspension when they were cultured in agar (CFUc). Values within the normal or close to normal range were reached in the mesenteric nodes of most of the animals transfused with 10 X 10(9) MBC or more. These values were obtained when 5 X 10(5) CFUc or more were transfused. Axillary nodes showed lower values than mesenteric nodes. They were mostly under the normal range but well over those of the irradiated controls. Frozen and thawed MBCs seem to be as effective as fresh cells for lymphopoietic restoration. The mesenteric nodes of dogs transfused with allogeneic MBCs showed higher cellularity and larger cortical-paracortical areas than those of dogs tranfused with approximately the same number of autologous cells. The repopulation of lymph nodes parallels that of the marrow.

Repopulation of lymph nodes of dogs after 1200 R whole-body x-irradiation and intravenous administration of mononuclear blood leukocytes

International Nuclear Information System (INIS)

Nelson, B.; Calvo, W.; Fliedner, T.M.; Herbst, E.; Bruch, C.; Schnappauf, H.P.; Flad, H.D.

1976-01-01

Fresh and cryopreserved autologous or allogeneic mononuclear blood cells (MBCs) intravenously injected in 1200 R total-body x-irradiated dogs repopulated lymph nodes within 10 days after transfusion. Several parameters of the lymphopoietic regeneration were correlated with the number of cells transfused and with the number of colony-forming units contained in the cell suspension when they were cultured in agar (CFU/sub c/). Values within the normal or close to normal range were reached in the mesenteric nodes of most of the animals transfused with 10 x 10 9 MBC or more. These values were obtained when 5 x 10 5 CFU/sub c/ or more were transfused. Axillary nodes showed lower values than mesenteric nodes. They were mostly under the normal range but well over those of the irradiated controls. Frozen and thawed MBCs seem to be as effective as fresh cells for lymphopoietic restoration. The mesenteric nodes of dogs transfused with allogeneic MBCs showed higher cellularity and larger cortical-paracortical areas than those of dogs transfused with approximately the same number of autologous cells. The repopulation of lymph nodes parallels that of the marrow

Transformation of bone marrow stem-cells and radiation-induced myeloid leukemia in mice

International Nuclear Information System (INIS)

Hirashima, K.; Bessho, M.; Hayata, I.; Nara, N.; Kawase, Y.; Ohtani, M.

1982-01-01

After a single whole-body X-irradiation of 300R to male RFM/MsNrs strain mice, the occurrence of myeloid leukemia initiated since four months and ceased at eleven months after irradiation. The cumulative incidence reached 24.5%. A time course study on the kinetics of pluripotential stem-cells (CFU-S) and granuloid committed stem-cells (CFU-C) in the marrow after 300R was also performed. The repopulation of CFU-S was accomplished within one month whereas that of CFU-C needed 210 days after irradiation. The incidence of leukemia was very rare after the complete repopulation of CFU-C. Simultaneously, collected spleen cells from the irradiated mice without overt leukemia were transplanted into 300-600R irradiated recipients of another sex. Three months thereafter, recipients were sacrificed to detect leukemic changes and the origin of leukemic cells by chromosome analysis. The results revealed that leukemic cell transformation of donor cells began 18 days after irradiation and on an average, 37.1% of the irradiated mice carried potentially leukemic cells for seven months after exposure, whereas none of the unirradiated mice carried leukemic cells at 7 months after irradiation. To investigate host factor(s) contributing to the proliferation of leukemic cells, the suppression of cellular immunity after 300R was measured by GVH mortality assay. However, the recovery of cellular immunity was observed until three months after irradiation and the role of cellular immunity to proliferation of leukemic cells after three months was negligible. (author)

Expression of T cell antigen receptor genes in the thymus of irradiated mice after bone marrow transplantation

International Nuclear Information System (INIS)

Matsuzaki, G.; Yoshikai, Y.; Kishihara, K.; Nomoto, K.

1988-01-01

Sequential appearance of the expression of T cell antigen receptor genes was investigated in the thymus of irradiated mice at the early stage after transplantation of Thy-1 congeneic H-2 compatible allogeneic bone marrow cells. The first cells to repopulate the thymus on day 7 after bone marrow transplantation were intrathymic radioresistant T cell precursors, which expanded mainly to CD4+CD8+ host-type thymocytes by day 14. A high level of gamma gene expression but a much reduced level of alpha and beta gene expression were detected in the host-type thymocytes on day 7. During regeneration of these cells, gamma-chain messages fell to low level and alpha and beta mRNA levels increased. The thymus of the recipients began to be repopulated by donor-derived T cells about 2 wk after bone marrow transplantation and was almost completely replaced by the third week. An ordered expression of gamma then beta and alpha-chain gene transcript was also observed in the donor-type thymocytes at the early stage after bone marrow transplantation. The use of thymocytes at early stage in whole-body irradiated bone marrow chimera provides a pertinent source for investigating the molecular mechanism of T cell differentiation in adult thymus

Decreased repopulation as well as increased reoxygenation contribute to the improvement in local control after targeting of the EGFR by C225 during fractionated irradiation.

NARCIS (Netherlands)

Krause, M.; Ostermann, G.; Petersen, C.; Yaromina, A.; Hessel, F.; Harstrick, A.; Kogel, A.J. van der; Thames, H.D.; Baumann, M.

2005-01-01

BACKGROUND AND PURPOSE: Inhibition of repopulation and enhanced reoxygenation has been suggested to contribute to improvement of local tumour control after fractionated irradiation combined with inhibitors of the epidermal growth factor receptor (EGFR). The present study addresses this hypothesis in

Dose-response studies of depletion and repopulation of rat intestinal mucosal mast cells after irradiation

International Nuclear Information System (INIS)

Sedgwick, D.M.; Ferguson, A.

1994-01-01

The effects of radiation on gut mucosal mast cells (MMC) and tissue eosinophils were examined. Groups of rats were given single doses of whole-body irradiation from 0.5 to 5 Gy. Serum rat mast cell protease II (RMCPII) concentration showed a significant dose-dependent fall after 1 Gy on day 3 and 1.5 Gy on day 7. MMC counts and tissue RMCPII values on day 7 decreased significantly by 70% after 1 Gy and were undetectable with larger doses. Rats with normal and expanded MMC populations were irradiated or given anaphylaxis. Serum RMCPII concentrations did not change after irradiation, but there was a 10-fold increase in RMCPII after anaphylaxis. Tissue eosinophils in jejunum were 50% of control at 7 days after 2 Gy, and this effect was progressively more marked with higher doses. Similar effects on MMC and eosinophils were demonstrated in ileum, ascending colon and rectum. After 4.5 Gy, repopulation of the gut with MMC did not occur until week 3-4 postirradiation and MMC counts were still 50% below those of controls at 5 weeks postirradiation. Counts of tisse eosinophils 5 weeks after 4.5 Gy irradiation had returned to control levels in jejunum but were still significantly depleted in colon. (Author)

Evaluation of stem cell reserve using serial bone marrow transplantation and competitive repopulation in a murine model of chronic hemolytic anemia

International Nuclear Information System (INIS)

Maggio-Price, L.; Wolf, N.S.; Priestley, G.V.; Pietrzyk, M.E.; Bernstein, S.E.

1988-01-01

Serial transplantation and competitive repopulation were used to evaluate any loss of self-replicative capacity of bone marrow stem cells in a mouse model with increased and persistent hemopoietic demands. Congenic marrows from old control and from young and old mice with hereditary spherocytic anemia (sphha/sphha) were serially transplanted at 35-day intervals into normal irradiated recipients. Old anemic marrow failed or reverted to recipient karyotype at a mean of 3.5 transplants, and young anemic marrow reverted at a mean of 4.0 transplants, whereas controls did so at a mean of 5.0 transplants. In a competitive assay in which a mixture of anemic and control marrow was transplanted, the anemic marrow persisted to 10 months following transplantation; anemic marrow repopulation was greater if anemic marrow sex matched with the host. It is possible that lifelong stress of severe anemia decreases stem cell reserve in the anemic sphha/sphha mouse marrow. However, marginal differences in serial transplantation number and the maintenance of anemic marrow in a competition assay would suggest that marrow stem cells, under prolonged stress, are capable of exhibiting good repopulating and self-replicating abilities

The effect of recovery from potentially lethal damage on the determination of repair and repopulation in a murine tumour

International Nuclear Information System (INIS)

Sheldon, P.W.; Fowler, J.F.

1985-01-01

Repair and repopulation following X irradiation of clamped-off murine anaplastic MT tumours was investigated using the established method of (Dsub(n)-D 1 )/(n-1). Repair was complete in 4 h, similar in extent to that reported in other tumours, and within the range of that reported for normal tissues. Subsequent repopulation commenced after 4 days and was equivalent to 1.8 Gy/day recovered dose, corresponding to a clonogenic cell number doubling time of 1.8 days. However, estimates of repair and repopulation may have been in error because the chronically hypoxic cells in this tumour alone have the ability to recover from potentially lethal damage (PLD) and so are more radioresistant than cells rendered acutely hypoxic by clamping. Because of this, even clamping off tumours at irradiation does not render all cell populations equally radioresistant, and so reoxygenation between fractions could result in an underestimate of repair and repopulation. Further, the differing sensitivity between acutely and chronically hypoxic cells renders the apparent OER a function of dose (i.e., oxygen not truly dose-modifying to chronically hypoxic cells). Consequently it is incorrect to assume a constant OER in order to compare repair in tumours irradiated under hypoxic conditions with that in normal tissues irradiated under aerobic conditions. (author)

Repopulation of the seminiferous epithelium of the rhesus monkey after X irradiation

International Nuclear Information System (INIS)

van Alphen, M.M.; van de Kant, H.J.; de Rooij, D.G.

1988-01-01

Repopulation of the seminiferous epithelium became evident from Day 75 postirradiation onward after doses of 0.5, 1.0, and 2.0 Gy of X rays. Cell counts in cross sections of seminiferous tubules revealed that during this repopulation the numbers of Apale (Ap) spermatogonia, Adark (Ad) spermatogonia, and B spermatogonia increased simultaneously. After 0.5 Gy the number of spermatogonia increased from approximately 10% of the control level at Day 44 to 90% at Day 200. After 1.0 and 2.0 Gy the numbers of spermatogonia increased from less than 5% at Day 44 to 70% at Days 200 and 370. The number of Ad and B spermatogonia, which are considered to be resting and differentiating spermatogonia, respectively, already had increased when the number of proliferating Ap spermatogonia was still very low. This early inactivation and differentiation of a large part of the population of Ap spermatogonia slows down repopulation of the seminiferous epithelium of the primates. By studying repopulating colonies in whole mounts of seminiferous tubules various types of colonies were found. In colonies consisting of only A spermatogonia, 40% of the A spermatogonia were found to be of the Ad type, which indicates that even before the colony had differentiated, 40% of the A spermatogonia were inactivated into Ad. Differentiating colonies were also found in which one or two generations of germ cells were missing. In some of those colonies it was found that the Ap spermatogonia did not form any B spermatogonia during one or two cycles of the seminiferous epithelium, while in other colonies all Ap spermatogonia present had differentiated into B spermatogonia. This indicates that the differentiation of Ap into B spermatogonia is a stochastic process

Effects of cell concentrations on the survival and repopulation of haemopoietic stem cells in irradiated bone marrow cell culture in vitro

International Nuclear Information System (INIS)

Fujitake, Hideki; Okamoto, Yuruko; Okubo, Hiroshi; Miyanomae, Takeshi; Kumagai, Keiko; Mori, K.J.

1981-01-01

Effects of cell concentrations on the survival and repopulation of haemopoietic stem cells after irradiation were studied in the long-term culture of mouse bone marrow cells in vitro. No difference was observed in the survival of the stem cells among cultures in which 0 - 10 7 cells were re-inoculated on the adherent cell colonies in the culture flask. Stem cells showed a significant proliferation within 1 week and the number of the stem cells exceeded the control in 3 weeks after irradiation in the cultures with less than 10 6 re-inoculated cells per flask. In contrast, there was a considerable delay in the onset of stem cell proliferation after irradiation in the culture with 10 7 cells per flask. Based on these results, a possibility that a stimulator of stem cell proliferation, released from irradiated stromal cells, is cancelled by an inhibitory factor produced by irradiated or unirradiated haemopoietic cells is postulated. (author)

Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification.

Science.gov (United States)

Douglas, Gillian; Van Kampen, Erik; Hale, Ashley B; McNeill, Eileen; Patel, Jyoti; Crabtree, Mark J; Ali, Ziad; Hoerr, Robert A; Alp, Nicholas J; Channon, Keith M

2013-11-01

Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell repopulation post-stenting, comparing the response of drug-eluting stents with a primary genetic modification to improve endothelial cell function. Endothelial cell repopulation was assessed en face in stented arteries in ApoE(-/-) mice with endothelial-specific LacZ expression. Stent deployment resulted in near-complete denudation of endothelium, but was followed by endothelial cell repopulation, by cells originating from both bone marrow-derived endothelial progenitor cells and from the adjacent vasculature. Paclitaxel-eluting stents reduced neointima formation (0.423 ± 0.065 vs. 0.240 ± 0.040 mm(2), P = 0.038), but decreased endothelial cell repopulation (238 ± 17 vs. 154 ± 22 nuclei/mm(2), P = 0.018), despite complete strut coverage. To test the effects of selectively improving endothelial cell function, we used transgenic mice with endothelial-specific overexpression of GTP-cyclohydrolase 1 (GCH-Tg) as a model of enhanced endothelial cell function and increased NO production. GCH-Tg ApoE(-/-) mice had less neointima formation compared with ApoE(-/-) littermates (0.52 ± 0.08 vs. 0.26 ± 0.09 mm(2), P = 0.039). In contrast to paclitaxel-eluting stents, reduced neointima formation in GCH-Tg mice was accompanied by increased endothelial cell coverage (156 ± 17 vs. 209 ± 23 nuclei/mm(2), P = 0.043). Drug-eluting stents reduce not only neointima formation but also endothelial cell repopulation, independent of strut coverage. In contrast, selective targeting of endothelial cell function is sufficient to improve endothelial cell repopulation and reduce neointima formation. Targeting endothelial cell function is a rational therapeutic strategy to improve vascular healing and decrease neointima formation after stenting.

Differential Secondary Reconstitution of In Vivo-Selected Human SCID-Repopulating Cells in NOD/SCID versus NOD/SCID/γ chainnull Mice

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Shanbao Cai

2011-01-01

Full Text Available Humanized bone-marrow xenograft models that can monitor the long-term impact of gene-therapy strategies will help facilitate evaluation of clinical utility. The ability of the murine bone-marrow microenvironment in NOD/SCID versus NOD/SCID/γ chainnull mice to support long-term engraftment of MGMTP140K-transduced human-hematopoietic cells following alkylator-mediated in vivo selection was investigated. Mice were transplanted with MGMTP140K-transduced CD34+ cells and transduced cells selected in vivo. At 4 months after transplantation, levels of human-cell engraftment, and MGMTP140K-transduced cells in the bone marrow of NOD/SCID versus NSG mice varied slightly in vehicle- and drug-treated mice. In secondary transplants, although equal numbers of MGMTP140K-transduced human cells were transplanted, engraftment was significantly higher in NOD/SCID/γ chainnull mice compared to NOD/SCID mice at 2 months after transplantation. These data indicate that reconstitution of NOD/SCID/γ chainnull mice with human-hematopoietic cells represents a more promising model in which to test for genotoxicity and efficacy of strategies that focus on manipulation of long-term repopulating cells of human origin.

Repopulation with IgA-containing cells of bronchial and intestinal lamina propria after transfer of homologous peyer's patch and bronchial lymphocytes

International Nuclear Information System (INIS)

Rudzik, R.; Clancy, R.L.; Perey, D.Y.E.; Day, R.P.; Bienenstock, J.

1975-01-01

Transfer of 50 million rabbit allogeneic lymphocytes from either bronchus-associated lymphoid tissue (BALT) or Peyer's patches into 1000 R x-irradiated recipients results, 6 days later, in predominant repopulation of gut and bronchial lamina propria, as well as spleen, with IgA-containing cells. After repopulation with BALT or Peyer's patch cells, lymphoid follicles in both gut and lung showed peripheral cellular membrane type of fluorescence with fluorescein-conjugated anti-IgA antisera only. Six days after x-irradiation alone, little evidence of repopulation was seen and immunofluorescent qualitative observations of gut and lung, and quantitative data in the spleen, confirmed these findings. After transfer of 50 million lymph node cells, very few immunoglobulin-containing cells were seen in the gut or bronchial lamina propria. These results suggest that there may be a common mucosal immunologic system, and that repopulation of gut and lung lamina propria may be through the organized lymphoid tissue therein. (U.S.)

The capacity of peripheral blood stem cells mobilised with chemotherapy plus G-CSF to repopulate irradiated marrow stroma in vitro is similar to that of bone marrow

International Nuclear Information System (INIS)

Demuynck, H.; Dexter, T.M.; Testa, N.G.; Pettengell, R.; Campos, E. de

1992-01-01

After treatment of patients with intermediate or high grade non-Hodgkin lymphoma with chemotherapy plus G-CSF the numbers of haemopoietic progenitor cells in the circulation increased to a mean of 226-fold for mixed CFC (Mix-CFC), 278-fold for GM-CFC and 29-fold for erythroid burst forming unit (BFU-E). The mean increase was modest (7-12-fold) for patients treated with chemotherapy alone. Peripheral blood mononuclear cells harvested at the time of the peak in the numbers of progenitors, or 2-4 days before the peak, seeded onto irradiated marrow stroma in vitro, repopulated the stroma and generated active haemopoiesis at least as effectively as bone marrow cells on a cell per cell basis. This is in contrast to the poor repopulating capacity of pretreatment blood. The results indicate that not only the progenitor cells, but also the repopulating stem cells migrated into the blood after chemotherapy plus G-CSF in sufficient numbers to allow harvesting and successful grafting without the possible complication of late haemopoietic failure. (author)

Modelling of tumour repopulation after chemotherapy

International Nuclear Information System (INIS)

Marcu, Loredana; Bezak, Eva

2010-01-01

Full text: While repopulation is a clinically observed phe nomenon after radiotherapy, repopulation of tumour cells between cycles of chemotherapy is usually a neglected factor in cancer treatment. As the effect of both radiotherapy and chemotherapy on tumour cells is the same (attack on cancer cells), the response of the tumour to injury and cell loss from the two treatment methods should be similar, including repopulation. Cell recruitment is known to be a possible mechanism responsible for tumour regrowth after radio therapy. The literature data regarding mechanisms of repopulation after chemotherapy is very limited. The current paper employs a Monte Carlo modelling approach to implement the pharmacokinetics of a widely used drug (cisplatin) into a previously developed vit1ual head and neck tumour and to study the effect of cisplatin on tumour regres sion and regrowth during treatment. The mechanism of cell recruitment was modelled by releasing various percentages (5-50%) of quiescent cells into the mitotic cycle after each chemotherapy cell kill. The onset of repopulation was also simulated, with both immediate onset and late onset of cell recruitment. Repopulation during chemotherapy, if occu ring, is a highly potent phenomenon, similar to drug resis tance, therefore it should not be neglected during treatment.

Human progenitor cells rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased frequency in comparison to cells from the same donor mobilized by granulocyte colony stimulating factor

DEFF Research Database (Denmark)

Hess, David A; Bonde, Jesper; Craft, Timothy P

2007-01-01

) or purified CD34(+) cells was compared at limiting dilution into NOD/SCID mice. Human AMD3100-mobilized MNC possessed enhanced repopulating frequency in comparison to G-CSF-mobilized MNC from paired donors, and purified CD34(+) progenitors were at least as efficient as the G-CSF mobilized cells....... The frequencies of NOD/SCID repopulating cells (SRC) were 1 SRC in 8.7 x 10(6) AMD3100-mobilized MNC compared to 1 SRC in 29.0 x 10(6) G-CSF-mobilized MNC, and 1 SRC in 1.2 x 10(5) AMD3100-mobilized CD34(+) cells compared to 1 SRC in 1.8 x 10(5) G-CSF-mobilized CD34(+) cells. Hematopoietic differentiation...

Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells

Science.gov (United States)

Butler, Jason M.; Nolan, Daniel J.; L.Vertes, Eva; Varnum-Finney, Barbara; Kobayashi, Hideki; Hooper, Andrea T.; Seandel, Marco; Shido, Koji; White, Ian A.; Kobayashi, Mariko; Witte, Larry; May, Chad; Shawber, Carrie; Kimura, Yuki; Kitajewski, Jan; Rosenwaks, Zev; Bernstein, Irwin D.; Rafii, Shahin

2010-01-01

Bone marrow endothelial cells (ECs) are essential for reconstitution of hematopoiesis, but their role in self-renewal of long term-hematopoietic stem cells (LT-HSCs) is unknown. We have developed angiogenic models to demonstrate that EC-derived angiocrine growth factors support in vitro self-renewal and in vivo repopulation of authentic LT-HSCs. In serum/cytokine-free co-cultures, ECs through direct cellular contact, stimulated incremental expansion of repopulating CD34−Flt3−cKit+Lineage−Sca1+ LT-HSCs, which retained their self-renewal ability, as determined by single cell and serial transplantation assays. Angiocrine expression of Notch-ligands by ECs promoted proliferation and prevented exhaustion of LT-HSCs derived from wild-type, but not Notch1/Notch2 deficient mice. In transgenic notch-reporter (TNR.Gfp) mice, regenerating TNR.Gfp+ LT-HSCs were detected in cellular contact with sinusoidal ECs and interfering with angiocrine, but not perfusion function, of SECs impaired repopulation of TNR.Gfp+ LT-HSCs. ECs establish an instructive vascular niche for clinical scale expansion of LT-HSCs and a cellular platform to identify stem cell-active trophogens. PMID:20207228

Immunity to Trichinella spiralis in irradiated mice

International Nuclear Information System (INIS)

Wakelin, D.; Wilson, M.M.

1980-01-01

Irradiation prevented the accelerated expulsion of Trichinella spiralis from mice immunized by transfer of immune mesenteric lymph node cells (IMLNC) or by prior infection. Nevertheless, worms in irradiated immune mice were smaller and less fecund than those in controls. In adoptively immunized and irradiated mice expulsion could not be achieved by increasing the numbers of IMLNC transferred, although the effect upon worm length was more severe. Thus IMLNC express a direct, anti-worm immunity which is independent of their role in worm expulsion. IMLNC cause expulsion in irradiated mice only when adequate levels of bone marrow-derived cells are available. The results are discussed in terms of a possible antibody-mediated basis for direct anti-worm immunity. (author)

Differential androgenesis in gamma irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Kim, Jihyang; Yoon, Yongdal [Hanyang Univ., Seoul (Korea, Republic of); Kim, Jin Kyu [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

2002-07-01

The Leydig cells of the testis account for at least 75% of the total testosterone produced in the normal adult male. Whereas the production of estrogen from androgen is catalyzed by aromatase cytochrome P450, which is found in many tissues, including gonad, brain, adipose tissue, bone, and heart. The gamma-irradiation causes the impairment of spermatogenesis and steroidogenesis in male mice. The present study was performed to analyze changes in testosterone concentrations and expression of steroidogenic enzyme of mice after whole body gamma-irradiation. Eight-week-old male ICR mice were irradiated with 6.5 or 10 Gy. At days 1, 2, 3, 4, and 5 after irradiation, testes were removed and processed for paraffin sections and isolation of mRNA. We calculated the gonad index from body and testis weight, and checked the testis volume. Hormonal analysis was performed by means of radioimmunoassay (RIA) in serum and intratesticular fluid. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression kinetics of the apoptotic gene and the cytochrome P450 aromatase gene after irradiation. In gamma-irradiated mice, the body weight reduced in comparison to that of the control group. Therefore, gonad indices increased. The testosterone concentrations in serum and intratesticular fluid were significantly reduced. RT- PCR data represented that the expression of Fas, Fas ligand, and aromatase cytochrome P450 showed the specific patterns against control groups. These results indicated that gamma- irradiation of adult mice induced the alteration of androgenesis and suggested that might counteract the spermatogenesis.

Genetic effects of feeding irradiated wheat to mice

International Nuclear Information System (INIS)

Vijayalaxmi

1976-01-01

The effects of feeding irradiated wheat in mice on bone marrow and testis chromosomes, germ cell numbers and dominant lethal mutations were investigated. Feeding of freshly irradiated wheat resulted in significantly increased incidence of polyploid cells in bone marrow, aneuploid cells in testis, reduction in number of spermatogonia of types A, B and resting primary spermatocytes as well as a higher mutagenic index. Such a response was not observed when mice were fed stored irradiated wheat. Also there was no difference between the mice fed un-irradiated wheat and stored irradiated wheat. (author)

Natural killer activity and suppressor cells in irradiated mice repopulated with a mixture of cells from normal and 89Sr-treated donors

International Nuclear Information System (INIS)

Levy, E.M.; Kumar, V.; Bennett, M.

1981-01-01

Mice that have been injected with 89 Sr have fairly normal B and T cell function, but are abnormal in that they lack natural killer (NK) activity and other functions that require an intact bone marrow. These mice also have an increased potential for suppressor cell activity. We had previously shown that spleen cells from 89 Sr-treated mice could transfer low NK activity and increased suppressor cell function to lethally irradiated syngeneic recipients. To investigate the mechanisms involved in perpetuating these defects, groups of normal spleen or bone marrow cells. Recipients were assayed for their NK activity and suppressor cell function 5 to 14 wk later. it was found that the addition of normal cells in the donor inoculum resulted in normal NK activity. This indicates that low NK activity in 89 Sr-treated mice was not due to the presence of a suppressor cell that prevented NK cell generation. It was additionally found that low NK activity in recipient mice could be boosted by interferon inducers. This would indicate that NK activity in the recipients was not due to a lack of interferon-sensitive pre-NK cells. Suppressor cell function in recipient mice depended on the type and number of normal cells in the donor inoculum. Bone marrow cells were very efficient in overcoming the tendency to produce suppressor cells. It took approximately 20 times more normal spleen cells to produce the same results. The implications of these findings are discussed

Usage of adenovirus expressing thymidine kinase mediated hepatocellular damage for enabling mouse liver repopulation with allogenic or xenogenic hepatocytes.

Directory of Open Access Journals (Sweden)

Daniel Moreno

Full Text Available It has been shown that the liver of immunodeficient mice can be efficiently repopulated with human hepatocytes when subjected to chronic hepatocellular damage. Mice with such chimeric livers represent useful reagents for medical and clinical studies. However all previously reported models of humanized livers are difficult to implement as they involve cross-breeding of immunodeficient mice with mice exhibiting genetic alterations causing sustained hepatic injury. In this paper we attempted to create chimeric livers by inducing persistent hepatocellular damage in immunodeficient Rag2(-/- γc(-/- mice using an adenovirus encoding herpes virus thymidine kinase (AdTk and two consecutive doses of ganciclovir (GCV. We found that this treatment resulted in hepatocellular damage persisting for at least 10 weeks and enabled efficient engraftment and proliferation within the liver of either human or allogenic hepatocytes. Interestingly, while the nodules generated from the transplanted mouse hepatocytes were well vascularized, the human hepatocytes experienced progressive depolarization and exhibited reduced numbers of murine endothelial cells inside the nodules. In conclusion, AdTk/GCV-induced liver damage licenses the liver of immunodeficient mice for allogenic and xenogenic hepatocyte repopulation. This approach represents a simple alternative strategy for chimeric liver generation using immunodeficient mice without additional genetic manipulation of the germ line.

Prenatal effects of ancestral irradiation in inbred mice

International Nuclear Information System (INIS)

Sprackling, L.E.S.

1975-01-01

Mice from 13 inbred strains (S, Z, E, Bab, BaB, BrR, C, K, N, Q, G, CFW, CF1) received continuous cobalt 60 irradiation at low dose rates for varying numbers of consecutive generations. Some Bab and BaB mice had received continuous irradiation for from 24 to 31 generations and the other mice had up to six generations of continuous irradiation in their ancestry. At weaning, the mice were removed from the irradiation room and were mated within strains either to sibs or nonsibs. Ancestral and direct irradiation doses were calculated. The ancestral dose was the effective accumulated dose to the progeny of the mated mice. The direct dose was the amount of irradiation received by any mated female from her conception to her weaning. Each irradiated or control female was scored as fertile or sterile and in utero litter counts were made in pregnant females that were dissected past the tenth day of pregnancy; the sum of moles, dead embryos, and live embryos was the total in utero litter size. A ratio of the living embryos to the total number of embryos in utero was determined for each litter. An increase in ancestral or direct irradiation dose significantly decreased fertility in 11 of the 13 strains. The fertility curves for the pooled data were sigmoid in the area of the doses below those that caused complete sterility. Among the controls, there were significant strain differences in total litter size and in the ratio. Strain X--Y plots, with ancestral or direct doses plotted against total litter size or ratio, revealed the tendency for litter size to decrease as dose increased. The only trend shown for ratio was for the litters with ratios of 0.50 or less to appear more frequently among the irradiated mice. The few corpora lutea counts revealed nothing of significance. Generally, there was a definite trend toward fewer mice alive in utero among the irradiated mice

Evaluation of hematopoietic potential generated by transplantation of muscle-derived stem cells in mice.

Science.gov (United States)

Farace, Francoise; Prestoz, Laetitita; Badaoui, Sabrina; Guillier, Martine; Haond, Celine; Opolon, Paule; Thomas, Jean-Leon; Zalc, Bernard; Vainchenker, William; Turhan, Ali G

2004-02-01

Muscle tissue of adult mice has been shown to contain stem cells with hematopoietic repopulation ability in vivo. To determine the functional characteristics of stem cells giving rise to this hematopoietic activity, we have performed hematopoietic reconstitution experiments by the use of muscle versus marrow transplantation in lethally irradiated mice and followed the fate of transplanted cells by Y-chimerism using PCR and fluorescence in situ hybridization (FISH) analysis. We report here that transplantation of murine muscle generate a major hematopoietic chimerism at the level of CFU-C, CFU-S, and terminally-differentiated cells in three generations of lethally irradiated mice followed up to 1 year after transplantation. This potential is totally abolished when muscle grafts were performed by the use of muscle from previously irradiated mice. As compared to marrow transplantation, muscle transplants were able to generate similar potencies to give rise to myeloid, T, B, and natural killer (NK) cells. Interestingly, marrow stem cells that have been generated in primary and then in secondary recipients were able to contribute efficiently to myofibers in the muscle tissue of tertiary recipients. Altogether, our data demonstrate that muscle-derived stem cells present a major hematopoietic repopulating ability with evidence of self-replication in vivo. They are radiation-sensitive and similar to marrow-derived stem cells in terms of their ability to generate multilineage hematopoiesis. Finally, our data demonstrate that muscle-derived hematopoietic stem cells do not lose their ability to contribute to myofiber generation after at least two rounds of serial transplantation, suggesting a potential that is probably equivalent to that generated by marrow transplantation.

Radioprotective effect of RSP-CM on mice irradiated with different doses

International Nuclear Information System (INIS)

Zhang Xia; Yang Rujun; Zhang Xin; Yang Yunfang; Jin Zhijun; Xiang Yingsong

2000-01-01

Objective: To investigate the radioprotective effects of cytokines on hematopoietic impairment of irradiated mice. Methods: Using RSP-CM and LP3-CM respectively originated GM-CSF and G-CSF to treat ICR mice irradiated with different doses of 60 Co γ-rays. The 30-day survival rate of mice, the mean survival days of dead mice were determined and the numbers of peripheral white blood cells and BMC of part of the mice were counted. At the same time, GM clonogenic activity of BM was assayed. Results:RSP-CM could effectively raise 30-day survival rate of mice irradiated with 7.5 Gy. However, LP3-CM had no obvious effect. Judging from the comparative survival ratio, only the RSP-CM treated group showed protective effect on the 8.0 Gy -irradiated mice. The 8.5 Gy-irradiated mice all died within 30 days, indicating that GM-CSF had weak effect on higher dose-irradiated mice. Conclusion: GM-CSF can stimulate the hematopoietic system of irradiated mice, and has dose-effect and time-effect relations. M-CSF used singly has no obvious effect

The entry of the prothymocyte into the thymus after lethal irradiation and bone marrow transplantation. 2

International Nuclear Information System (INIS)

Mulder, A.H.; Visser, J.W.M.; Zoetelief, J.; Bekkum, D.W. van

1988-01-01

The time of entry of prothymocytes into the thymus after lethal irradiation and bone marrow transplantation (BMT) was determined by exposing the thymus only or the whole body with the thymus shielded to a second irradiation after different intervals. The repopulation of the thymus by donor type cells was determined by a thymus repopulation assay using donor specific markers. Reirradiation of the thymus kills the prothymocytes that have entered the thymus during the interval. It was found that reirradiation of the thymus from 48 hours after BMT onwards increasingly delayed thymus regeneration. This shows that donor prothymocytes do not enter the thymus until about 2 days after BMT and that they continue to do so during at least 3 subsequent days. In the second reirradiation protocol thymus regeneration occurred earlier in the shielded thymus than in thymuses of whole body irradiated mice. Earlier thymus regeneration was not seen in mice that were reirradiated at 24 hours after BMT, but occurred only when irradiation took place at 48 hours and later. These data are consistent with those obtained in the first protocol. The results are in contradiction with results of direct homing experiments, which showed entrance of donor cells within 3 hours after BMT. A functional assay demonstrated that the early appearing cells cannot be prothymocytes. In retransplantation experiments it was shown that the bone marrow may indeed be the initial homing site of prothymocytes. 14 refs.; 5 figs.; 1 table

Influence of intensity of bone marrow erythropoietic activity on radiosensitivity of mice. Part 2. Effects of carbon monoxide induced hypererythropoiesis and polycythemia on ability of bone marrow to restitute erythropoiesis in irradiated recipients

International Nuclear Information System (INIS)

Kwiek, S.

1986-01-01

Hypererythropoiesis was induced in mice by exposure to carbon monoxide, and they got polycythemic after transfer to normal air. Erythropoietic repopulation ability (ERA) of transplanted bone marrow decreased to one-third by day 6 of carbon monoxide hypoxia, and returned to normal level during subsequent polycythemia. These changes did not correlate with alteration of CFU-S counts. The found discrepances are ascribed to lack of unipotential erythroid progenitor cells in hypererythropoietic bone marrow. Possibility of assessment of the part of ERA due to the latter cells on the basis of parallel determinations of ERA and CFU-S counts in polycythemic and hypererythropoietic or normal mice is discussed. Complete lack of endogenous haemopoietic macrocolonies was noted in irradiated polycythemic mice. The cells constituting the cellular basis of ERA were found to be insensitive to hydroxyurea. 13 refs., 3 tabs. (author)

Enhanced normal short-term human myelopoiesis in mice engineered to express human-specific myeloid growth factors.

Science.gov (United States)

Miller, Paul H; Cheung, Alice M S; Beer, Philip A; Knapp, David J H F; Dhillon, Kiran; Rabu, Gabrielle; Rostamirad, Shabnam; Humphries, R Keith; Eaves, Connie J

2013-01-31

Better methods to characterize normal human hematopoietic cells with short-term repopulating activity cells (STRCs) are needed to facilitate improving recovery rates in transplanted patients.We now show that 5-fold more human myeloid cells are produced in sublethally irradiated NOD/SCID-IL-2Receptor-γchain-null (NSG) mice engineered to constitutively produce human interleukin-3, granulocyte-macrophage colony-stimulating factor and Steel factor (NSG-3GS mice) than in regular NSG mice 3 weeks after an intravenous injection of CD34 human cord blood cells. Importantly, the NSG-3GS mice also show a concomitant and matched increase in circulating mature human neutrophils. Imaging NSG-3GS recipients of lenti-luciferase-transduced cells showed that human cells being produced 3 weeks posttransplant were heterogeneously distributed, validating the blood as a more representative measure of transplanted STRC activity. Limiting dilution transplants further demonstrated that the early increase in human granulopoiesis in NSG-3GS mice reflects an expanded output of differentiated cells per STRC rather than an increase in STRC detection. NSG-3GS mice support enhanced clonal outputs from human short-term repopulating cells (STRCs) without affecting their engrafting efficiency. Increased human STRC clone sizes enable their more precise and efficient measurement by peripheral blood monitoring.

Radioprotective effects of a preparation (HemoHIM) of herb mixture on self-renewal tissues and immune system in mice

Energy Technology Data Exchange (ETDEWEB)

Jo, Sung Kee; Park, Hae Ran; Jung, Uhee; Oh, Heon [KAERI, Taejon (Korea, Republic of); Kim, Sung Ho [Chonnam National Univ. Seoul (Korea, Republic of); Yee, Sung Tae [Sunchon National Univ., Seoul (Korea, Republic of)

2004-07-01

A preparation (HemoHIM) of herb mixture was designed to protect the gastrointestine and hematopoietic organs and to promote recovery of the immune system against radiation damage. The mixture of 3 edible medicinal herbs was decocted with hot water and the extract was fractionated with ethanol. The preparation HemoHIM was made up with addition of ethanol-insoluble fraction to the total water extract. In vitro, HemoHIM, its polysaccharide and ethanol fractions protected lymphocytes against radiation and scavenged hydroxyl radicals. The proliferation of lymphocytes and bone marrow cells by HemoHIM was due to its polysaccharide fraction. In mice administered with the preparation (HemoHIM) before gamma-irradiation the jejunal crypt survival was increased and the apoptosis of crypt cells was decreased. HemoHIM administration increased the survival of bone marrow stem cells and promoted the repopulation of blood cells following irradiation. In the analysis of the repopulated lymphocyte subsets, B cells were firstly regenerated and then T cells were recovered in mice administrated with HemoHIM. The antibody production against T-dependent antigen DNP-KLH was augmented by HemoHIM in irradiated mice. Finally, oral or intraperitoneal administration of HemoHIM augmented the 30 day survival rate after irradiation. These results indicated that HemoHIM, a preparation of the herb mixture, protected the stem cells of self-renewal tissues and hematopoietic organs and promoted recovery of the immune system against radiation damage, thus increasing the survival following lethal irradiation. Since the preparation of herb mixture is a relatively nontoxic natural product, it might be a useful modifier for prevention and control of radiation damages.

Mechanisms of an increased level of serum iron in gamma-irradiated mice

International Nuclear Information System (INIS)

Xie, Li-hua; Zhang, Xiao-hong; Hu, Xiao-dan; Min, Xuan-yu; Zhou, Qi-fu; Zhang, Hai-qian

2016-01-01

The potential mechanisms underlying the increase in serum iron concentration in gamma-irradiated mice were studied. The gamma irradiation dose used was 4 Gy, and cobalt-60 ( 60 Co) source was used for the irradiation. The dose rate was 0.25 Gy/min. In the serum of irradiated mice, the concentration of ferrous ions decreased, whereas the serum iron concentration increased. The concentration of ferrous ions in irradiated mice returned to normal at 21 day post-exposure. The concentration of reactive oxygen species in irradiated mice increased immediately following irradiation but returned to normal at 7 day post-exposure. Serum iron concentration in gamma-irradiated mice that were pretreated with reduced glutathione was significant lower (p < 0.01) than that in mice exposed to gamma radiation only. However, the serum iron concentration was still higher than that in normal mice (p < 0.01). This change was biphasic, characterized by a maximal decrease phase occurring immediately after gamma irradiation (relative to the irradiated mice) and a recovery plateau observed during the 7th and 21st day post-irradiation, but serum iron recovery was still less than that in the gamma-irradiated mice (4 Gy). In gamma-irradiated mice, ceruloplasmin activity increased and serum copper concentration decreased immediately after irradiation, and both of them were constant during the 7th and 21st day post-irradiation. It was concluded that ferrous ions in irradiated mice were oxidized to ferric ions by ionizing radiation. Free radicals induced by gamma radiation and ceruloplasmin mutually participated in this oxidation process. The ferroxidase effect of ceruloplasmin was achieved by transfer of electrons from ferrous ions to cupric ions. (orig.)

Cycling G1 CD34+/CD38+ cells potentiate the motility and engraftment of quiescent G0 CD34+/CD38-/low severe combined immunodeficiency repopulating cells.

Science.gov (United States)

Byk, Tamara; Kahn, Joy; Kollet, Orit; Petit, Isabelle; Samira, Sarit; Shivtiel, Shoham; Ben-Hur, Herzl; Peled, Amnon; Piacibello, Wanda; Lapidot, Tsvee

2005-04-01

The mechanism of human stem cell expansion ex vivo is not fully understood. Furthermore, little is known about the mechanisms of human stem cell homing/repopulation and the role that differentiating progenitor cells may play in these processes. We report that 2- to 3-day in vitro cytokine stimulation of human cord blood CD34(+)-enriched cells induces the production of short-term repopulating, cycling G1 CD34(+)/CD38(+) cells with increased matrix metalloproteinase (MMP)-9 secretion as well as increased migration capacity to the chemokine stromal cell-derived factor-1 (SDF-1) and homing to the bone marrow of irradiated nonobese diabetic severe/combined immunodeficiency (NOD/SCID) mice. These cycling G1 cells enhance SDF-1-mediated in vitro migration and in vivo homing of quiescent G0 CD34(+) cells, which is partially abrogated after inhibition of MMP-2/-9 activity. Moreover, the engraftment potential of quiescent G0 SCID repopulating cells (SRCs) is also increased by the cycling G1 CD34(+)/CD38(+) cells. This effect is significantly abrogated after incubation of cycling G1 cells with a neutralizing anti-CXCR4 antibody. Our data suggest synergistic interactions between accessory cycling G1 CD34(+)/CD38(+) committed progenitor cells and quiescent, primitive G0 CD34(+)/CD38(-/low) SRC/stem cells, the former increasing the motility and engraftment potential of the latter, partly via secretion of MMP-9.

Effect of ultraviolet irradiation on mast cell-deficient W/Wv mice

International Nuclear Information System (INIS)

Ikai, K.; Danno, K.; Horio, T.; Narumiya, S.

1985-01-01

The effect of UV irradiation on the skin was investigated in (WB-W/+) X (C57BL/6J-Wv/+)F1-W/Wv mice, which are genetically deficient in tissue mast cells. Their congenic littermates (+/+) and normal albino mice (ICR or BALB/c) were used as controls. Mice were irradiated with 500 mJ/cm2 of UVB and the increment of ear thickness was measured before and 6, 12, and 24 h after irradiation. Ear swelling in W/Wv mice at 12 and 24 h after irradiation was significantly smaller than that in +/+ and ICR mice. In contrast, the number of sunburn cells formed 24 h after UVB irradiation (200 or 500 mJ/cm2) was similar in W/Wv, +/+ and ICR mice. On the other hand, when mice were treated with 8-methoxy-psoralen (0.5%) plus UVA irradiation (4 J/cm2) (topical PUVA), ears of W/Wv and BALB/c mice, which were both white in color, were thickened similarly 72 h after treatment, but less swelling was observed in +/+ mice, which were black in skin color. The amount of prostaglandin D2 (PGD2) in ears, determined by radioimmunoassay specific for PGD2, was elevated 3-fold in +/+ and ICR mice at 3 h after irradiation with 500 mJ/cm2 of UVB in comparison with basal level without irradiation. However, such elevation was not observed in W/Wv mice. These results suggest that mast cells play an important role in UVB-induced inflammation, and PGs from mast cells are responsible at least in part for the development of this reaction. However, neither mast cells nor PGs contribute to the sunburn cell formation and ear swelling response by PUVA treatment

Protection effect of ginkgo albumin extract on γ-ray irradiated mice

International Nuclear Information System (INIS)

Deng Qianchun; Duan Huike; Wang Lan; Xie Bijun; Chen Chunyan

2005-01-01

Water soluble ginkgo albumin extract (GAE), which was extracted for the first time from seeds of Ginkgo bilbo L in our laboratory has good antioxidant and anti-aging activity. In this paper, protective effect of GAE on γ-rays irradiated mice was studied. The results showed that the mice irradiated to 8.5 Gy were zero, whereas survival rate of the high dosage GAE group was 20 percent. Blood picture of the 8.5 Gy irradiated mice suffered damages of different degrees, while blood picture index of the GAE group decreased slower and recovered faster significantly than the irradiation control group. GAE and Vitamin C could significantly enhance serum SOD activity in serum and increase DNA content in bone marrow cells, and also promote recovery of damaged immunology function of the irradiated mice. These suggest that GAE may protect mice from the radiation damages by enhancement of antioxidant activity, hemopoiesis function and immunologic function of mice. (authors)

Radioprotective effect of chitosan in sub-lethally X-ray irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Nishimura, Yoshikazu; Ikota, Nobuo; Arima, Hiromi; Watanabe, Yoshito; Yukawa, Masae; Ozawa, Toshihiko [National Inst. of Radiological Sciences, Chiba (Japan); Kim, Hee-Sun [Korea Hydro and Nuclear Power Corp., Seoul (Korea, Republic of). Radiation Health Research Inst.; Bom, Hee-Seung; Kim, Young-Ho [Chonnam Univ., Kwangju (Korea, Republic of). Hospital

2003-03-01

The radioprotective effect of chitosan was studied in mice following whole-body X-ray irradiation. C3H/He mice were exposed to 7 Gy, and their survival rates were examined. The survival rates of chitosan-diet mice were about 20% higher than those of mice on a standard diet, and the rates dropped sharply to a plateau at day 10 after X-ray irradiation. The chitosan-diet mice had an increased weight ratio of spleen to body within the experimental period. The leukocyte, thrombocyte, and erythrocyte counts as well as the hematocrit and hemoglobin levels were recovered significantly and more rapidly in the chitosan-diet mice than the standard-diet mice at day 14 after irradiation. The scavenging abilities of chitosan were evaluated by the electron spin resonance (ESR) spin-trapping method. These observations suggested that chitosan led to hematopoetic activation and leuko-cytogenesis in mice after sub-lethal dose irradiation, and that the biological response might be caused by radical trapping or scavenging. (author)

The early effects in the brain after irradiation with carbon ions using mice

International Nuclear Information System (INIS)

Takai, Nobuhiko; Nakamura, Saori; Ohba, Yoshihito; Uzawa, Akiko; Furusawa, Yoshiya; Koike, Sachiko; Matsumoto, Yoshitaka; Hirayama, Ryoichi

2011-01-01

This study investigated both early and late effects in the brain after irradiation with carbon ions using mice. The irradiation dose was set at level known to produce vascular change followed by necrosis, which appeared the late period after irradiation with 30 Gy. The whole of brain was irradiated, excluding eyes and brain stem. The mice irradiated with single dose of 30 Gy showed deficit in short-term working memory assessed at 36 hr after irradiation, whereas mice receiving carbon irradiation showed no deficit in long-term reference memory. At 16 weeks after irradiation, the irradiated mice showed marked learning impairment compared with age-matched controls and the irradiated mice showed substantial impairment of working memory. Histopathological observation revealed no abnormal finding in the irradiated brain at 36 hr after irradiation, although irradiated mice showed marked neuronal degeneration at the hippocampus within CA1 to CA3 layers at 16 weeks after irradiation. In the irradiated group, neuronal cells in the hippocampal CA1-3 areas were reduced by 30-49%. These results suggest that although irradiation-induced hippocampal degeneration is associated with learning disability, cognitive deficits may also be detected on the early stage, not associated with hippocampal degeneration. (author)

The effect of embryonal thymic calf extracts on neonatally thymectomized mice and on mice lethally irradiated with gamma rays

International Nuclear Information System (INIS)

Czaplicki, J.; Blonska, B.; Stec, L.

1981-01-01

The effect of embryonal thymic calf extracts (ETCE) on mice thymectomized at birth was investigated. ETCE was found to induce an increase in leukopenia and decrease in the level of serum gamma globulins; it also reduced survival time in mice. The effect of ETCE on lethally irradiated mice was also examined. Only long-term administration of ETCE prior to gamma irradiation at 750 rad prolonged the survival time of mice (40% permanent survival) as compared with irradiated controls; the leukocytes from mice retained mitotic capability. Neither long-term treatment with ETCE prior to irradiation at 1000 rad, nor short-term administration prior to 750 rad affected survival time. ETCE administered after irradiation of mice with 750 rad caused a rapid decrease in blood leukocytes and a significantly lowered survival time. (Auth.)

The effect of local irradiation on the immune response in mice. I. Effect of sham-irradiation

International Nuclear Information System (INIS)

Gauci, C.L.; Gerber, M.; Dubois, J.-B.; Serrou, B.

1979-01-01

In C57BL/6 mice exposed to 1600 rads to the left foot pad, an important decrease of non-specific inflammatory responsiveness initiated by the injection of oyster glycogen into the peritoneal cavity was observed on the one hand and a diminution of the delayed hypersensitivity response following tuberculin injection, on the other hand. Nevertheless, the same immunosuppression was noted both in sham irradiated mice and in those receiving hydrocortisone. In irradiated mice this transient immunosuppression was related to a normal adrenal function. Bi-laterally adrenalectomised mice did not exhibit this reaction which reappeared after hydrocortisone administration. The reduction of delayed hypersensitivity is irrespective of the irradiated zone, but the duration of immune depression is longer in irradiated than in unirradiated tissue. During the depression of delayed hypersensitivity response an increase in the number of splenic B-lymphocytes and macrophages and a decrease of the number of splenic T-lymphocytes was observed these observations suggest that immunosuppression following irradiation is related to acute stress

Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma.

Science.gov (United States)

Wu, Licun; Blum, Walter; Zhu, Chang-Qi; Yun, Zhihong; Pecze, Laszlo; Kohno, Mikihiro; Chan, Mei-Lin; Zhao, Yidan; Felley-Bosco, Emanuela; Schwaller, Beat; de Perrot, Marc

2018-04-27

Cancer cell repopulation during chemotherapy or radiotherapy is a major factor limiting the efficacy of treatment. Cancer stem cells (CSC) may play critical roles during this process. We aim to demonstrate the role of mesothelioma stem cells (MSC) in treatment failure and eventually to design specific target therapies against MSC to improve the efficacy of treatment in malignant mesothelioma. Murine mesothelioma AB12 and RN5 cells were used to compare tumorigenicity in mice. The expression of CSC-associated genes was evaluated by quantitative real-time PCR in both cell lines treated with chemo-radiation. Stemness properties of MSC-enriched RN5-EOS-Puro2 cells were characterized with flow cytometry and immunostaining. A MSC-specific gene profile was screened by microarray assay and confirmed thereafter. Gene Ontology analysis of the selected genes was performed by GOMiner. Tumor growth delay of murine mesothelioma AB12 cells was achieved after each cycle of cisplatin treatment, however, tumors grew back rapidly due to cancer cell repopulation between courses of chemotherapy. Strikingly, a 10-times lower number of irradiated cells in both cell lines led to a similar tumor incidence and growth rate as with untreated cells. The expression of CSC-associated genes such as CD24, CD133, CD90 and uPAR was dramatically up-regulated, while others did not change significantly after chemoradiation. Highly enriched MSC after selection with puromycin displayed an increasing GFP-positive population and showed typical properties of stemness. Comparatively, the proportion of MSC significantly increased after RN5-EOS parental cells were treated with either chemotherapy, γ-ray radiation, or a combination of the two, while MSC showed more resistance to the above treatments. A group of identified genes are most likely MSC-specific, and major pathways related to regulation of cell growth or apoptosis are involved. Upregulation of the gene transcripts Tnfsf18, Serpinb9b, Ly6a

Rate of lens lesion development and the age of mice at time of irradiation

International Nuclear Information System (INIS)

Gajewski, A.K.; Majewska, K.; Slowikowska, M.G.

1976-01-01

The rate of lens lesion development has been studied in mice irradiated at different age ranging from one day up to one year old mice. The time needed for the first appearance of lens lesion was shortest in groups of mice irradiated at the age of one, two and three days of life, and longest in groups of mice irradiated at the age of 5 days, 1 week and 2 weeks of life. The time needed for the first appearance of lens lesion for mice irradiated between the third week and one year of life was constant. It was longer than for mice irradiated during the first three days of life and shorter than for mice irradiated at 5 up to 14 days of life. In all but one irradiated groups the age at which the first lens lesion occurred differed significantly from the age at which the first senile changes occurred in the lens of control mice. The one exception was the group of mice irradiated at the age of one year. (author)

Apoptosis in spermatogonia irradiated P53 null mice

International Nuclear Information System (INIS)

Streit-Bianchi, M.; Hendry, J.H.; Roberts, S.A.; Morris, J.D.; Durgaryan, A.A.

2007-01-01

Complete text of publication follows. The exposure of germ cells to ionizing radiations is of concern both from high-dose therapeutic exposures and from low doses causing deleterious trans-generational mutations. P53 protein plays an important role in cellular damage and is expressed in the testis normally during meiosis, its expression being localised to the preleptotene and early/mid pachytene spermatocytes. P53 null mice, heterozygotes possessing a 129 Sv/C57BL6 genetic background and B6D2F1 mice have been irradiated to 1 and 2 Gy single doses. Fractionated exposures of 1+1 Gy at 4 hours interval were also carried out. Apoptosis induction, spermatogonia and spermatocytes survival were assessed by microscope analysis of histological samples at 4 to 96 hours after irradiation in time-course experiments. The same end-points were also assessed at 72 and 96 hours after irradiation to single doses in the region between 20cGy to 2Gy. A dose dependent level of p53 expression was observed at 4 hours after irradiation to 1 and 2 Gy which returned to normal level by 24 hours. Our data support a two process mode of apoptosis with a first wave around 12 hours followed by a second wave at 2-3 days. The first wave apoptosis is substantially reduced in p53 null mice whereas the second wave is reduced in B6D2F1 mice. The initial increase in apoptosis was delayed in some stages of the of germ cells development which were identified by the spermatids shape. Clear correlation exists between apoptosis and survival assessed in stage XI-XII Tubules 72 hours after irradiation. The data are in agreement with other data in literature indicating that irradiated spermatogonia die through apoptosis. The lack of apoptosis observed in p53 null mice results in a very high survival rate of daughter cells assessed later. Theses spermatocytes and the following progenitor cells are likely to carry mutations as most will not die in the smaller second wave of apoptosis observed 3 days after

Changes with age in swimming performance of X-irradiated mice

International Nuclear Information System (INIS)

Norimura, T.; Yoshikawa, I.; Okajima, S.

1980-01-01

The time required to swim 250 cm was determined once weekly for the entire life of fifteen pairs of male dd/K mice. The irradiated group was exposed to a single 224 rad of X-rays at 20 weeks of age. Median survival time (ST 50 ) for the control was 88.9 weeks and that for the irradiated group was 77.4 weeks, and both regression lines relating to death rate and age were parallel. The swimming ability of control mice began to decrease when the mice were 40 weeks of age, after which there was a gradual reduction with age at 0.00646/day. In the irradiated group, the swimming ability decreased from seven weeks after irradiation. The time of 50% reduction of swimming speed (TRS 50 ) for the control was 78.9 weeks and that for the irradiated group was 66.3 weeks, and the slopes of the regression lines relating reduction rate and age were similar. Differences between ST 50 and TRS 50 were 10 weeks in the control and 11 weeks in the irradiated group, respectively. These results indicate that there is no basic difference in the reduction in swimming ability between control and irradiated mice. The X-irradiation may simply mean that the reduction in the swimming ability is displaced to an earlier time with no alteration in the rate of reduction, and that the earlier appearance in the irradiated group is related to premature aging as induced by irradiation. (author)

Bacterial repopulation of drinking water pipe walls after chlorination.

Science.gov (United States)

Mathieu, Laurence; Francius, Grégory; El Zein, Racha; Angel, Edith; Block, Jean-Claude

2016-09-01

The short-term kinetics of bacterial repopulation were evaluated after chlorination of high-density polyethylene (HDPE) colonized with drinking water biofilms and compared with bare HDPE surfaces. The effect of chlorination was partial as a residual biofilm persisted and was time-limited as repopulation occurred immediately after water resupply. The total number of bacteria reached the same levels on both the bare and chlorinated biofilm-fouled HDPE after a seven-day exposure to drinking water. Due to the presence of a residual biofilm, the hydrophobicity of chlorinated biofilm-fouled surface exhibited much lower adhesion forces (2.1 nN) compared to bare surfaces (8.9 nN). This could explain the rapid repopulation after chlorination, with a twofold faster bacterial accumulation rate on the bare HDPE surface. γ-Proteobacteria dominated the early stages of repopulation of both surfaces and a shift in the dominance occurred over the colonization time. Such observations define a timescale for cleaning frequency in industrial environments and guidelines for a rinsing procedure using drinking water.

Dominant lethal mutations in male mice fed γ-irradiated diet

International Nuclear Information System (INIS)

Chauhan, P.S.; Aravindakshan, M.; Aiyer, A.S.; Sundaram, K.

1975-01-01

Three groups of Swiss male mice were fed a stock ration of an unirradiated or irradiated (2.5 Mrad) test diet for 8 wk. After the feeding period, the males were mated with groups of untreated female mice for 4 consecutive weeks. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. Numbers of dead implantations, including deciduomas and dead embryos, showed no significant differences among the different groups, thus producing no evidence of any induced post-implantation lethality in mice fed on irradiated diet. Similarly, there was no indication of preimplantation lethality, since implantation rates remained comparable among different groups. Consumption of irradiated diet did not affect the fertility of mice. Total pre- and post-implantation loss, as indicated by the numbers of live implantations remained comparable among all the groups of mice. (author)

The effect of thymus cells on bone marrow transplants into sublethally irradiated mice

International Nuclear Information System (INIS)

Kruszewski, J.A.; Szcylik, C.; Wiktor-Jedrzejczak, W.

1984-01-01

Bone marrow cells formed similar numbers of 10-days spleen colonies in sublethally (6 Gy) irradiated C57B1/6 mice as in lethally (7.5 Gy) irradiated mice i.e. approximately 20 per 10 5 cells. Numbers of 10 day endogenous spleen colonies in sublethally irradiated mice (0.2 to 0.6 per spleen) did not differ significantly from the numbers in lethally irradiated mice. Yet, transplants of 10 7 coisogenic marrow cells into sublethally irradiated mice resulted in predominantly endogenous recovery of granulocyte system as evidenced by utilization of ''beige'' marker for transplanted cells. Nevertheless, transplanted cells engrafted into sublethally irradiated mice were present in their hemopoietic tissues throughout the observation period of 2 months never exceeding 5 to 10% of cells. Thymus cells stimulated endogenous and exogenous spleen colony formation as well as endogenous granulopoietic recovery. Additionally, they increased both the frequency and absolute numbers of graft-derived granulocytic cells in hemopoietic organs of transplanted mice. They failed, however, to essentially change the quantitative relationships between endogenous and exogenous hemopoietic recovery. These results may suggest that spleen colony studies are not suitable for prediction of events following bone marrow transplant into sublethally irradiated mice. Simultaneously, they have strengthened the necessity for appropriate conditioning of recipients of marrow transplants. (orig.) [de

Effect of head-irradiation upon epidermal mitotic activity during wound healing in the adrenalectomized mice

International Nuclear Information System (INIS)

Kobayashi, Koshi

1977-01-01

Epidermal mitotic activity during wound healing was estimated both in the adrenalectomized, head-irradiated mice and in the adrenalectomized, non-irradiated mice, and was compared with those obtained previously from the unoperated, head-irradiated mice. It was found that head-irradiation caused a mitotic depression to a much smaller extent in the adrenalectomized mice than it did in the unoperated mice, though adrenalectomy itself had exerted a great inhibitory effect upon the mitosis induced by an injury. Whether this abscopal effect of head-irradiation upon the mitotic activity was mediated via the adrenals, and whether in the adrenalectomized mice the head-irradiation acted to increase epidermal response to injury, making the mitotic pattern of adrenalectomized mice to come near that of control mice were discussed. (auth.)

Effects of low-dose rate irradiation on two types of type II diabetes model mice

International Nuclear Information System (INIS)

Nomura, Takaji; Sakai, Kazuo

2004-01-01

The effects of low-dose rate gamma-irradiation were investigated in two mouse strains - C57BL/KsJ-db/db (db mouse) and AKITA (AKITA mouse)-for type II diabetes mellitus. Both strains develop the developed type II diabetes by about 8 weeks of age due to dysfunction of the insulin/insulin receptor. The db Mouse' shows obese and exhibits hyperinsulinism, and the onset of Type II diabetes like resembles that for Westerners. On the other hand, the AKITA mouse has exhibits disordered insulin secretion, and the diabetes such as resembles that of Asians. Ten-week old female mice, in groups of 8 or 12, were irradiated at 0.65 mGy/hr in the low-dose rate irradiation facility in the Low Dose Radiation Research Center. The level of urine glucose was measured with test slips. The urine glucose levels of all of the mice were highly elevated the beginning of the irradiation. In the irradiated group of db mice, three mice showed decrease in glucose level compare to the level of non-irradiated diabetes mice after 35, 52 or 80 weeks of irradiation. All had maintained a normal level thereafter. No such improvement in diabetes was ever observed in the 12 mice of in the non-irradiated control group. The AKITA mice, however, did not decrease the glucose level regardless of the irradiation. Both the db mice and AKITA mice had their lives prolonged their life by the irradiation. The survival rate of db mice at the age of 90 weeks was 75% in the irradiated group, but 50% in the non-irradiated group. The average life span was 104 weeks in the irradiated group and 87 weeks in the control group. Furthermore, a marked difference was furthermore observed in the appearance of the coat hair, skin, and tail; appearances were well preserved in the irradiated group. The average life span in the irradiated AKITA mice was also longer than that for the non-irradiated mice, 51 weeks and 41 weeks in the irradiated and non-irradiated group respectively. These results suggest that the low-dose irradiation

Radioprotection of mice by lactoferrin against irradiation with sublethal X-rays

International Nuclear Information System (INIS)

Nishimura, Yoshikazu; Homma-Takeda, Shino; Kim, Hee-Sun; Kakuta, Izuru

2014-01-01

The influence of a host defense protein, lactoferrin (LF), contained in exocrine secretions such as milk, on radiation disorder was investigated. A total of 25 C3H/He mice in each of two groups were maintained with 0.1% LF-added and LF-free diets, respectively, for one month. The mice were then treated with single whole-body X-ray irradiation at a sublethal dose (6.8 Gy), and the survival rate after irradiation was investigated. The survival rate at 30 d after irradiation was relatively higher in the LF group than in the control group (LF-free), (85 and 62%, respectively). The body weight 15 d after X-ray irradiation was also significantly greater in the LF group than in the control group. The hemoglobin level and hematocrit value were higher in the LF group at 5 d before X-ray irradiation. Another 52 mice underwent whole-body X-ray irradiation at the sublethal dose (6.8 Gy), and then LF was intraperitoneally injected once at 4 mg/animal to half of them. The survival rate in LF-treated mice 30 d after irradiation was 92%, significantly higher than in mice treated with saline (50%) (P = 0.0012). In addition, LF showed hydroxyl radical scavenger activity in vitro. These findings suggest that LF may inhibit radiation damage. (author)

Life shortening and carcinogenesis in mice irradiated at the perinatal period with gamma rays

International Nuclear Information System (INIS)

Sasaki, S.; Kasuga, T.

1986-01-01

This study elucidates the life-span radiation effects in mice irradiated at the perinatal period in comparison to mice irradiated at the young adult period. B6C3F 1 female mice were irradiated at 17 days of prenatal age, at 0 days of postnatal age, or as young adults at 15 weeks of age with 190, 380, or 570 rads of 137 Cs gamma rays. Mice irradiated at the late fetal period showed dose-dependent life shortening of somewhat lesser magnitude than that seen after neonatal or young adult irradiation. Mice exposed at the late fetal period were highly susceptible to induction of pituitary tumors for which the latent period was the longest of all induced neoplasms. Incidence of lung tumors in mice irradiated at the late fetal period with 190 and 380 rads was higher than in controls. Malignant lymphomas of the lymphocytic type developed in excess, after a short latent period, in mice irradiated fetally with the highest dose; susceptibility of prenatally exposed mice was lower than that of early postnatally exposed mice. Liver tumors developed more frequently in mice irradiated in utero than in controls; susceptibility to induction of this type of neoplasm was highest at the neonatal period. In general, carcinogenic response of mice exposed at the late fetal period resembled that of neonatally exposed mice but was quite different from that of young adult mice. Mice exposed as young adults have no, or low, susceptibility to induction of pituitary, lung, and liver tumors; and a higher susceptibility to induction of myeloid leukemias and Harderian gland tumors. 19 refs., 4 figs., 3 tabs

Functional State of Haemopoietic Stem Cells in the Irradiated Mouse

Energy Technology Data Exchange (ETDEWEB)

Silini, G.; Pozzi, Laura V. [Laboratorio di Radiobiologica Animale, Centro Studi Nucleari, Casaccia, Rome (Italy)

1968-08-15

The repopulation kinetics of bone marrow in irradiated (C3H x C57BL) F{sub 1} hybrid mice were followed at different time intervals after a single whole-body dose of 150 rad X -rays. The changes in the number of total nucleated cells and of colony-forming cells were estimated and expressed as number of cells per femur shaft of fixed length. For the evaluation of the progenitor cell compartment an exogenous test of transplantation into heavily irradiated hosts followed by spleen colony counts was employed. In an attempt to distinguish between cycling and dormant cells in the progenitor pool, vinblastine was also administered under various schedules of treatment with respect to time and dosage to follow the changes induced by this drug in the irradiated recovering marrow. The depopulation of total bone-m arrow cells caused by vinblastine proceeded at a comparable rate in both the irradiated and the normal mouse. On the other hand, depopulation of the colony-formers is faster in animals irradiated 1 -2 days previously as compared with normal animals or mice irradiated 1 week or 2 weeks earlier. The data were interpreted to show that in the marrow of a newly-irradiated animal more cells are in a fast cycle than in a normal or a recovering animal. Data are finally presented and discussed concerning the use of vinblastine for studies of stem cell kinetics in haemopoietic tissues. (author)

Reduction of allergenicity of irradiated ovalbumin in ovalbumin-allergic mice

International Nuclear Information System (INIS)

Seo, Ji-Hyun; Lee, Ju-Woon; Kim, Jae-Hun; Byun, Eui-Baek; Lee, Soo-Young; Kang, Il-Jun; Byun, Myung-Woo

2007-01-01

Egg allergy is one of the most serious of the immediate hypersensitivity reactions to foods. Such an allergic disorder is mediated by IgE antibodies stimulated by T-helper type 2 (Th2) lymphocytes. This study was undertaken to evaluate changes of allergenicity and cytokine profiles by exposure of irradiated ovalbumin (OVA), a major allergen of egg white, in the OVA-allergic mice model. OVA solutions (2 mg/ml in 0.01 M phosphate buffered saline (PBS) were gamma-irradiated to 50 and 100 kGy. The allergenicity in the OVA-allergy-induced mice model was remarkably reduced when challenged with irradiated OVA. Cultures of spleen cells harvested from OVA-sensitized mice showed a significant decrease in Th2 cytokine levels of ILs-4 and -5 with a concomitant increase in Th1 cytokine levels of IL-12 when co-cultured with irradiated OVA. However, IFN-γ level decreased dependant on the radiation dose of co-cultured OVA. The levels of IgEs and Th2-cytokine were reduced dependant on the radiation dose. These data show that the irradiated OVA could downregulate the activity of Th2 lymphocytes in OVA-sensitized mice

Radiation damage, repopulation and cell recovery analysis of in vitro tumour cell megacolony culture data using a non-Poissonian cell repopulation TCP model

International Nuclear Information System (INIS)

Stavrev, P; Weldon, M; Warkentin, B; Stavreva, N; Fallone, B G

2005-01-01

The effects of radiation damage, tumour repopulation and cell sublethal damage repair and the possibility of extracting information about the model parameters describing them are investigated in this work. Previously published data on two different cultured cell lines were analysed with the help of a tumour control probability (TCP) model that describes tumour cell dynamics properly. Different versions of a TCP model representing the cases of full or partial cell recovery between fractions of radiation, accompanied by repopulation or no repopulation were used to fit the data and were ranked according to statistical criteria. The data analysis shows the importance of the linear-quadratic mechanism of cell damage for the description of the in vitro cell dynamics. In a previous work where in vivo data were analysed, the employment of the single hit model of cell kill and cell repopulation produced the best fit, while ignoring the quadratic term of cell damage in the current analysis leads to poor fits. It is also concluded that more experiments using different fractionation regimes producing diverse data are needed to help model analysis and better ranking of the models

Evidence for the re-establishment of a heterogeneity in radiosensitivity among spermatogonial stem cells repopulating the mouse testis following depletion by X-rays

International Nuclear Information System (INIS)

Cattanach, B.M.; Barlow, J.H.

1984-01-01

Earlier studies have shown that the spermatogonial stem cells of the mouse testis recovering from previous radiation or chemical mutagen exposure give subnormal yields of genetic damage with subsequent X-irradiation. This response has been investigated further: (a) with a high, 9-Gy X-ray dose given 4, 12 or 21 days after a 1-Gy conditioning dose and (b) with a 1 + 7-Gy, 24-h fractionation regime given 4 or 14 days after a 1-Gy conditioning dose. The results of the experiments suggest that a heterogeneity in radiosensitivity, such as exists in unirradiated stem cell populations and absent 24-48 h after radiation depletion, is quickly re-established among the stem cells repopulating the testis. And that the newly established heterogeneity is removed by the second 1-Gy conditioning dose. With longer intervals between treatments, genetic yields consistent with additivity were obtained in Expt. 1; less clear results were obtained in Expt. 2. Comparison with earlier data generally suggested that the duration of the repopulating period is dose-dependent. In a third experiment evidence was obtained that genetic damage induced by X-irradiation can be reduced by a subsequent treatment with triethylenemelamine (TEM) during the repopulating phase. This confirmed an earlier finding. Such an interaction could not be demonstrated with two X-ray treatments. An explanation for the X-ray/TEM interaction is offered. (Auth.)

Experimental transmission of M. leprae into the testes of mice born from 60Co-irradiated pregnant mice

International Nuclear Information System (INIS)

Sushida, Kiyo; Tanemura, Mutsuko

1979-01-01

R 1 -mice, which were born from pregnant mice (R-P) irradiated with 60 CO 300 R were inoculated with leprosy bacilli into the testis. Recently, the author reported that the skin homograft survival duration in 60 CO-irradiated mice (R-P) was shown to be longer than the duration in the R 1 -F mice. The acid-fast bacilli, the so-called globi, were often found at the inoculated site of R-P mice, but not in the R 1 -F mice. The R 1 -F females bred with normal males and the R 2 -F females bred with normal males were both irradiated with 60 CO 300 R, and the R 2 -F male offspring from this R 1 -F and the R 3 -F male offspring from this R 2 -F showed the same increase in sensitivity to leprosy bacilli as the R-P generation. Acid-fast bacilli (globi, +G) were also found in the testes of the R 2 -F and R 3 -F males. IR-F mice which had received 131 I-Na 100 μci injections and also 60 CO 300 R irradiations during their fetus-term, showed few increase in sensitivity to infection of leprosy bacilli. (author)

Radioprotective effects of Cordyceps sinensis extracts on {gamma}-irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Yoo, Beong Gyu [Wongwang Health Science College, Iri (Korea, Republic of); Kim, On Joong; Kim, Jae Young [Dongguk University, Seoul (Korea, Republic of)

1999-06-01

Effect of single intraperitoneal administration of Cordyceps sinensis (Cs) extract at 24 hour before whole-body {gamma} - irradiation on the survival ratio, body weight, organ weight changes and serum metabolites in the irradiated mice were investigated. The single pre-administration of Cs extract increased the 40-day survival ration of irradiated mice from 66.7 percent to 83.4 percent. The administration of Cs extract completely prevented weight reductions of spleen and thymus produced by {gamma} - irradiation (P < 0.05, P < 0.01). Similar but somewhat less radioprotective effect was also found in the testis of the Cs treated mice. The administration of Cs inhibited the serum hyperglycemia produced by irradiation on the day 7th(P < 0.01). However, it did not influence the serum cholesterol and protein levels on the days examined. The present study is the first report regarding Cs which was tested and found to be radioprotective. (Author)

Radioprotective effects of Cordyceps sinensis extracts on γ-irradiated mice

International Nuclear Information System (INIS)

Yoo, Beong Gyu; Kim, On Joong; Kim, Jae Young

1999-01-01

Effect of single intraperitoneal administration of Cordyceps sinensis (Cs) extract at 24 hour before whole-body γ - irradiation on the survival ratio, body weight, organ weight changes and serum metabolites in the irradiated mice were investigated. The single pre-administration of Cs extract increased the 40-day survival ration of irradiated mice from 66.7 percent to 83.4 percent. The administration of Cs extract completely prevented weight reductions of spleen and thymus produced by γ - irradiation (P < 0.05, P < 0.01). Similar but somewhat less radioprotective effect was also found in the testis of the Cs treated mice. The administration of Cs inhibited the serum hyperglycemia produced by irradiation on the day 7th(P < 0.01). However, it did not influence the serum cholesterol and protein levels on the days examined. The present study is the first report regarding Cs which was tested and found to be radioprotective. (Author)

Ginsan activated the antioxidant defense systems in irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Song, Jie Young; Son, Soo Jung; Ahn, Ji Yeon; Shim, Ji Young; Han, Young Soo; Jung, In Sung; Yun, Yeon Sook [KIRMS Daegu (Korea, Republic of)

2003-07-01

Ginsan, a polysaccharide extracted from Panax ginseng, has hematopoietic activity and is also known as a good biological-response modifier. In this investigation, we studied the effects of ginsan on the {gamma}-radiation induced alterations of some antioxidant systems in spleen of Balb/c mice. There are many data that irradiation induces Reactive Oxygen Species (ROS), which plays an important causative role in radiation damage of cell. The level of ROS in cells is regulated by enzymatic and nonenzymatic antioxidant systems. The most powerful ones among them are superoxide dismutases (SODs) catalyzing the dismutation of superoxide anion radical o{sub 2} to H{sub 2}O{sub 2}, catalase deactivating h-2O{sub 2} and reduced glutathion (GSH) detoxifying H{sub 2}O{sub 2} and other ROS> At the 5{sub th} day after sublethal whole body irradiation, splenocytes of irradiated mice expressed only marginally increased levels of Mn-SOD, however, Cu/Zn-SOD, catalase, thioredoxine reductase (TR) and thioredoxine (TRX) mRNA (135% increase compared to control), however, the combination of irradiation with ginsan increased the SODs and GPX production more effectively. In addition to the above results, we obtained the similar data of protein expression. The enzyme activities of SOD, catalase, and GPX of ginsan-treated and irradiated mice were significantly enhanced by 140, 115, 126% respectively, compared with those of irradiated mice. Based on these results, we propose that the induction of antioxidant enzymes of ginsan is at least in part due to its capacity to protect against radiation.

Reproductive function in mice exposed to ancestral and direct irradiation

International Nuclear Information System (INIS)

Nash, D.J.; Sprackling, L.S.

1978-01-01

Reproduction was studied in 13 inbred strains of mice that had been exposed continuously to 60 Co gamma radiation for varying numbers of generations. At weaning the mice were removed from the irradiation chamber and were tested for reproductive performance. Ancestral and direct levels of irradiation were determined for each animal. Each irradiated or control female was scored as fertile or sterile, and in utero litter counts were made in pregnant females that were dissected past the 10th day of pregnancy. The number of resorptions, dead embryos, and live embryos were counted, and the ratio of living embryos to the total number of embryos was determined for each litter. The overall fertility curves were sigmoid in the range of doses below those which caused complete sterility, which indicated some sort of cumulative damage. In 11 of the 13 strains studied, an increase in ancestral and/or direct irradiation led to significant decreases in fertility. The means of the number alive in the litters for the control and irradiated mice in each strain showed a definite trend toward fewer live mice in utero after irradiation. Least-squares analyses of variance were made to detect possible effects of any of six irradiation variables (ancestral linear, ancestral quadratic, ancestral cubic, direct linear, direct quadratic, or direct cubic) or of strain differences on total litter size and on ratio. Strain effects were significant in each instance. Litter size was more likely to be affected by radiation variables than ratios were

A comparison of foamy and lentiviral vector genotoxicity in SCID-repopulating cells shows foamy vectors are less prone to clonal dominance

Directory of Open Access Journals (Sweden)

Elizabeth M Everson

2016-01-01

Full Text Available Hematopoietic stem cell (HSC gene therapy using retroviral vectors has immense potential, but vector-mediated genotoxicity limits use in the clinic. Lentiviral vectors are less genotoxic than gammaretroviral vectors and have become the vector of choice in clinical trials. Foamy retroviral vectors have a promising integration profile and are less prone to read-through transcription than gammaretroviral or lentiviral vectors. Here, we directly compared the safety and efficacy of foamy vectors to lentiviral vectors in human CD34+ repopulating cells in immunodeficient mice. To increase their genotoxic potential, foamy and lentiviral vectors with identical transgene cassettes with a known genotoxic spleen focus forming virus promoter were used. Both vectors resulted in efficient marking in vivo and a total of 825 foamy and 460 lentiviral vector unique integration sites were recovered in repopulating cells 19 weeks after transplantation. Foamy vector proviruses were observed less often near RefSeq gene and proto-oncogene transcription start sites than lentiviral vectors. The foamy vector group were also more polyclonal with fewer dominant clones (two out of six mice than the lentiviral vector group (eight out of eight mice, and only lentiviral vectors had integrants near known proto-oncogenes in dominant clones. Our data further support the relative safety of foamy vectors for HSC gene therapy.

The influence of Listeria monocytogenes cells on the primary immunologic response in irradiated mice

International Nuclear Information System (INIS)

Borowski, J.; Jokoniuk, P.

1977-01-01

The influence of killed Listeria monocytogenes cells on the primary immunologic response in mice irradiated with 300 or 500 R was studied. The immunologic response of the mice to sheep red blood cells used as antigen was assessed at the cellular level (by counting PFC) and humoral level. Injection of killed Listeria monocytogenes cells before irradiation of the mice diminished the immunosuppressive effect of roentgen radiation. Injection of the cells after irradiation accelerated regeneration of immunologic reactivity in the irradiated mice. (author)

Effects of ginger extract on testis enzymes of X-ray irradiated mice

International Nuclear Information System (INIS)

Zhao Shuhua; Li Jingshun; Wang Chunhua; Pan Qin; Yang Qiong

2005-01-01

Objective: To research the effects of extract of ginger on testis enzymes of X-ray irradiated mice. Methods: Mice were treated with three different doses of extract of ginger: high dose (9.3 mL·kg -1 ), middle dose (4.7 mL·kg -1 ), and low dose (2.3 mL·kg -1 ). All mice were irradiated once with 2.0 Gy X-ray. At the same time, the negative group (treated with vegetable oil only) and positive one (irradiated as well as extract of ginger groups after treated with vegetable oil) were set up. The changes of activities of enzymes in testes of mice were observed. Results: After irradiated, in the group of high dose the activity of G-6-PD was decreased but the activity of LDH was increased (P 0.05). In every group, SDH had no significant difference (P>0.05). Conclusion: The proper dose of extract of ginger has significant effects on stabilization of testis enzymes of X-ray irradiated mice. (authors)

Radioprotective effect of cimitidine on acutely irradiated mice survival and hematopoietic system

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Qing-rong WANG

2017-02-01

Full Text Available Objective　To investigate the radioprotective effect of cimetidine on survival rate and hematopoietic system in acutely irradiated mice. Methods　The total body irradiation doses were 6.0Gy and 8.0Gy respectively at 1.01Gy/min rate. Sixty healthy male C57BL/6 mice were randomly divided into control group, model group, positive-drug (523 group and cimetidine groups (33.3mg/kg, 100mg/kg and 300mg/kg. Each group had ten mice. The mice were given intragastric administration of cimetidine for 6d before the irradiation in cimetidine groups, and 523 was administered before irradiation once a day for one day in 523 group, and at 5h after irradiation, was given again. The 30d survival rate after 8.0Gy irradiation was recorded. The peripheral blood cells, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMNPCE were determined 30d after 6.0Gy irradiation. Results　After 8.0Gy irradiation, all the mice died on 21th day in model control group. The survival rates in cimetidine groups were 50%, 20% and 30%, respectively. After 6.0Gy irradiation on 30th day, compared with control group, the peripheral white blood cells (WBC and bone marrow DNA content were decreased significantly (P<0.01, P<0.05 in model group, and fMNPCE was increased significantly (P<0.05. Compared with model group, WBC was significantly increased in 300mg/kg cimetidine group (P<0.01. In cimetidine groups, the bone marrow DNA content was increased significantly after irradiation (P<0.01 or P<0.05, and the fMNPCE was decreased significantly (P<0.01 or P<0.05and tended towards normal. Conclusion　Cimetidine could improve 30d survival rate of acutely irradiated mice and has good protective effect on hematopoietic system. DOI: 10.11855/j.issn.0577-7402.2017.01.12

Radioprotective effects of melatonin on carbon-ion and X ray irradiation in mice

International Nuclear Information System (INIS)

Saito, Masayoshi; Kawata, Tetsuya; Liu, C.; Sakurai, Akiko; Ito, Hisao; Ando, Koichi

2004-01-01

The radioprotective ability of melatonin was investigated in C3H mice irradiated to a whole-body X-ray (150 Kv, 20 mA) and carbon-ion (290 MeV/u). Mice exposed to X-ray, 13 KeV/μm and 50 KeV/μm carbon-ion dose of 7.0-7.5 Gy, 6.5-7.25 Gy and 6.0-6.5 Gy, respectively. One hour before the irradiation, mice were given an intraperitoneal injection of 0.2 ml of either solvent (soybean oil) or melatonin (250 mg/kg, uniform suspension in soybean oil). Mice were observed for mortality over a period of 30 days following irradiation. Results obtained the first year are as follows. The toxicity of melatonin (at a dose 250 mg/kg) intraperitoneal administered to mice could not be observed. A pretreatment of melatonin is effective in protecting mice from lethal damage of low-linear energy transfer (LET) irradiation (X-ray and 13 KeV/μm carbon-ion). In the high-LET irradiated mice with 50 KeV/μm carbon-ion, melatonin exhibited a slight increase in their survival. (author)

Late effects of chronic low dose-rate γ-rays irradiation on mice

International Nuclear Information System (INIS)

Tanaka, Satoshi; Sasagawa, Sumiko; Ichinohe, Kazuaki; Matsumoto, Tsuneya; Otsu, Hiroshi; Sato, Fumiaki

2002-01-01

To evaluate late biological effects of chronic low dose-rate radiation, we are conducting two experiments. Experiment 1 - Late effects of chronic low dose-rate g-rays irradiation on SPF mice, using life-span and pathological changes as parameters. Continuous irradiation with g-rays for 400 days was performed using 137 Cs γ-rays at dose-rates of 20 mGy/day, 1 mGy/day and 0.05 mGy/day with accumulated doses equivalent to 8,000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. As of 2002 March 31, 3,999 of the total 4,000 mice have died. Preliminary analyses of data show that 20 mGy/day suggested a shortened life span in both sexes. Partial results show that the most common lethal neoplasms in the pooled data of non-irradiated control and irradiated male mice, in order of frequency, were neoplasms of the lymphohematopoietic system, liver, and lung. In female mice, neoplasms of the lymphohematopoietic system, soft tissue, and endocrine system were common. Experiment 2 - Effects on the progeny of chronic low dose-rate g-ray irradiated SPF mice: pilot study, was started in 1999 and is currently in progress. (author)

Stability in Effects of gamma-Irradiated Chinese Medicinal Prescriptions on Protection of Mice from Radiation

International Nuclear Information System (INIS)

Yang Jung-Ah; Kim Sung-Ho

2000-01-01

The radioprotective effects of irradiated medicinal plants on biological system were studied to apply the irradiation technology for hygienic purpose that is usually performed by chemical preservatives. We previously reported that the three Chinese medicinal prescriptions, Si-Wu-Tang, Bu-Zhong-Yi-Qi-Tang and San-Ling-Bai-Shu-San, showed radioprotective effects in mice. In these experiments, to investigate the difference in radioprotective effects between irradiated (10 kGy) and non-irradiated medicinal plants, mice were administered with the irradiated or non-irradiated prescriptions and then the mice were exposed to gamma-rays with low and high dosage. Non-exposed mice were also prepared as a control. The effects of prescriptions on the jejunal crypt survival, endogenous spleen colony formation, and apoptosis of jejunal crypt cells in mice were investigated after exposure. All of the prescriptions showed the protective effects of the jejunal crypt (p0.05) and the adminstration of the prescriptions increased the formation of endogenous spleen colony (p0.05) and reduced the frequency of radiation-induced apoptosis (p0.05). No significant difference in effects between irradiated and non-irradiated prescreption on the parameters was found in mice administered with each prescription before exposure to gamma-rays. In non-exposed mice, there were no different findings in the parameters between irradiated and non-irradiated prescription

Effect of pulmonary irradiation from inhaled 90Y on immunity to Listeria monocytogenes in mice

International Nuclear Information System (INIS)

Sanchez, A.; Lundgren, D.L.; McClellan, R.O.

1976-01-01

The immunological response of mice subjected to irradiation from particles deposited in the lungs and challenged with Listeria monocytogenes was investigated. Mice, exposed by inhalation to 90 Y (a beta-emitting radionuclide) in relatively insoluble fused aluminosilicate particles, were immunized with L. monocytogenes either before or after exposure. Two additional groups of mice were either immunized or irradiated only. A group of control mice received no irradiation or immunization. The beta radiation dose absorbed by the lungs of each mouse at time of challenge averaged 10,000 rads. Fourteen days after immunization, all mice were challenged with 2 LD 50 doses of L. monocytogenes via the respiratory route. Survival of all immunized mice either with or without exposure to 90 Y varied from 90 to 100% as compared to 10 to 20% for the mice irradiated only and for control mice through 14 days after challenge. Pulmonary clearance of inhaled L. monocytogenes during the first 4 hr after challenge was suppressed in the mice irradiated only but not in those immunized only, or in the immunized and irradiated groups, and control mice. There appeared to be a suppression of proliferation of L. monocytogenes in lungs and spleen in the immunized groups 72 hr after challenge, whereas the lungs and spleens of the mice irradiated only and the control mice had extensive bacterial invasion. It was concluded that the 10,000 rads of beta radiation absorbed by the lungs did not suppress the immune mechanisms of the immunized mice

Effect of semiconductor GaAs laser irradiation on pain perception in mice

Energy Technology Data Exchange (ETDEWEB)

Zarkovic, N.; Manev, H.; Pericic, D.; Skala, K.; Jurin, M.; Persin, A.; Kubovic, M.

1989-01-01

The influence of subacute exposure (11 exposures within 16 days) of mice to the low power (GaAs) semiconductive laser-stimulated irradiation on pain perception was investigated. The pain perception was determined by the latency of foot-licking or jumping from the surface of a 53 degrees C hot plate. Repeated hot-plate testing resulted in shortening of latencies in both sham- and laser-irradiated mice. Laser treatment (wavelength, 905 nm; frequency, 256 Hz; irradiation time, 50 sec; pulse duration, 100 nsec; distance, 3 cm; peak irradiance, 50 W/cm2 in irradiated area; and total exposure, 0.41 mJ/cm2) induced further shortening of latencies, suggesting its stimulatory influence on pain perception. Administration of morphine (20 mg/kg) prolonged the latency of response to the hot plate in both sham- and laser-irradiated mice. This prolongation tended to be lesser in laser-irradiated animals. Further investigations are required to elucidate the mechanism of the observed effect of laser.

Adrenaline and serotonin therapeutic effect on the hemopoietic system of irradiated mice

International Nuclear Information System (INIS)

Smirnova, I.B.; Dontsova, G.V.; Rakhmanina, O.N.; Konstantinova, M.M.

1984-01-01

Post-irradiation effect of adrenaline and serotonin on the hemopoietic system of irradiated mice has been studied. The pharmaceuticals were injected subcutaneously 15 minutes before the X-radiation exposure at a dose of 7 Gy or immediately after it. The degree of radiation injury has been estimated from 30-day survival fraction of the animals, cell state of the bone marrow, mass of spleen, cfu quantity in the bone marrow at exo- and endocolonial growth (following implantation of bone marrow cells from mice that had been injected with these drugs to irradiated recipients). Post-irradiation effect of adrenaline turned to be weaker than that of serotonin, the latter increasing the survival rate of irradiated mice to 50%. It is stated that post-irradiation therapeutic effect of adrenaline and serotonin expressed in acceleration of the irradiated hemopoietic tissue repair can be realized under direct effect of drugs on the viable hemopoietic cells, probably, by enchancement of their proliferation

Effect of local x-irradiation on mice reproduction in two successive generations

International Nuclear Information System (INIS)

Strel'nikova, N.K.; Lisenkova, L.N.

1978-01-01

For an experimental assessment of the biologic effectiveness of a single exposure to local irradiation exposure in simulating the conditions of exposure in X ray studies, an experiment was carried out on white mice. Mice of two successive generations were exposed to local X irradiation in the eye region. The radiation was found to bring about changes in the reproductive function (such as sterility, reduced litter size and fertility of females); these changes being dose-dependent in a nonlinear manner. The biologic effect of irradiation was greater in the second-generation mice

Effects on the glucose metabolism in type II diabetes model mice treated with dose-rates irradiation

International Nuclear Information System (INIS)

Nomura, Takaharu; Sakai, Kazuo

2004-01-01

The effects of low-dose rate gamma-irradiation on the type II diabetes mellitus were investigated in C57BL/KsJ-ab/db (db mouse). This mouse develops the type II diabetes within 8 weeks of the birth due to a dysfunction of the insulin receptors. As a result the db mouse shows obese and exhibits hyperinsulinism. Ten-week old female mice (12 mice in each group) were irradiated with gamma-rays at 0.35 mGy/hr, 0.65 mGy/hr or 1.2 mGy/hr in the low-dose rate irradiation facility in the Low Dose Radiation Research Center. The level of plasma glucose and insulin was measured. After 2 weeks irradiation, the glucose level slightly increased, however the difference between the irradiated mice and non-irradiated groups was not significant. The plasma insulin concentration decreased in the non-irradiated group to half of the initial level. In the irradiated group, it also decreased but in the group of 0.65 mGy/hr and 0.35 mGy/hr, it was significantly differed from that in the non-irradiated group. In the glucose tolerance test, plasma glucose level increased shortly after 0.1 mg/head glucose injection by mouth and reached to a peak at 90-120 min after the injection. The glucose level of the non-irradiated mice was slightly higher than that of irradiated mice. The plasma insulin level of non-irradiated group was enhanced after the injection and maintained the level during the test. However the levels of irradiated mice were decreased at 30-60 min after the injection. Both the level of non-irradiated an irradiated was almost same but the non-irradiated one was a little high. In all of mice, the plasma insulin level was highly elevated right after the 0.05 units/head insulin injection by i.p. and the levels were also gradually decreased. The level of the non-irradiated group was slowly decreased and was higher than the irradiated mice. The plasma glucose levels of all mice did not change after the test; however, the levels of irradiated mice were slightly lower than that of non-irradiated

Studies on the mutagenic and cytogenetic effects of irradiated wheat in mice

International Nuclear Information System (INIS)

Reddy, P.P.; Reddi, O.S.; Ebenezer, D.N.; Naidu, N.V.; Goud, S.N.

1978-01-01

A series of experiments were conducted to test the mutagenic and cytogenetic potentials of freshly and stored irradiated wheat in mice. In the first series, the effects of feeding of CBA mice for 8 weeks with the diet containing 60% of wheat freshly irradiated ( 3 H/He mice were undertaken. Feeding of both freshly and stored irradiated wheat showed neither an increase in dominant lethals and chromosomal aberrations nor a reduction in germ cells. In another series, the reproductive performance of the CBA females fed stored irradiated (75 krad) wheat was investigated and it was observed that the average total number of litters and the litter size did not vary from those of the females fed unirradiated wheat. (author)

Effect of bifidobacteria implantation on the survival time of whole-body irradiated mice

International Nuclear Information System (INIS)

Yokokura, Teruo; Onoue, Masaharu; Mutai, Masahiko

1980-01-01

Letahl dose (2 KR) of gamma-ray was irradiated on the whole bodies of mice. Survival time after irradiation was significantly longer in mice with administration of both Bifidobacterium breve YIT 4008 and transgalactosyl oligosaccharide than in mice with administration of either of the two or nothing. (Tsunoda, M.)

Quiescent Oct4+ Neural Stem Cells (NSCs) Repopulate Ablated Glial Fibrillary Acidic Protein+ NSCs in the Adult Mouse Brain.

Science.gov (United States)

Reeve, Rachel L; Yammine, Samantha Z; Morshead, Cindi M; van der Kooy, Derek

2017-09-01

Adult primitive neural stem cells (pNSCs) are a rare population of glial fibrillary acidic protein (GFAP) - Oct4 + cells in the mouse forebrain subependymal zone bordering the lateral ventricles that give rise to clonal neurospheres in leukemia inhibitory factor in vitro. pNSC neurospheres can be passaged to self-renew or give rise to GFAP + NSCs that form neurospheres in epidermal growth factor and fibroblast growth factor 2, which we collectively refer to as definitive NSCs (dNSCs). Label retention experiments using doxycycline-inducible histone-2B (H2B)-green fluorescent protein (GFP) mice and several chase periods of up to 1 year quantified the adult pNSC cell cycle time as 3-5 months. We hypothesized that while pNSCs are not very proliferative at baseline, they may exist as a reserve pool of NSCs in case of injury. To test this function of pNSCs, we obtained conditional Oct4 knockout mice, Oct4 fl/fl ;Sox1 Cre (Oct4 CKO ), which do not yield adult pNSC-derived neurospheres. When we ablated the progeny of pNSCs, namely all GFAP + dNSCs, in these Oct4 CKO mice, we found that dNSCs did not recover as they do in wild-type mice, suggesting that pNSCs are necessary for dNSC repopulation. Returning to the H2B-GFP mice, we observed that the cytosine β-d-arabinofuranoside ablation of proliferating cells including dNSCs-induced quiescent pNSCs to proliferate and significantly dilute their H2B-GFP label. In conclusion, we demonstrate that pNSCs are the most quiescent stem cells in the adult brain reported to date and that their lineage position upstream of GFAP + dNSCs allows them to repopulate a depleted neural lineage. Stem Cells 2017;35:2071-2082. © 2017 AlphaMed Press.

High-energy proton irradiation of C57Bl6 mice under hindlimb unloading

Science.gov (United States)

Mendonca, Marc; Todd, Paul; Orschell, Christie; Chin-Sinex, Helen; Farr, Jonathan; Klein, Susan; Sokol, Paul

2012-07-01

Solar proton events (SPEs) pose substantial risk for crewmembers on deep space missions. It has been shown that low gravity and ionizing radiation both produce transient anemia and immunodeficiencies. We utilized the C57Bl/6 based hindlimb suspension model to investigate the consequences of hindlimb-unloading induced immune suppression on the sensitivity to whole body irradiation with modulated 208 MeV protons. Eight-week old C57Bl/6 female mice were conditioned by hindlimb-unloading. Serial CBC and hematocrit assays by HEMAVET were accumulated for the hindlimb-unloaded mice and parallel control animals subjected to identical conditions without unloading. One week of hindlimb-unloading resulted in a persistent, statistically significant 10% reduction in RBC count and a persistent, statistically significant 35% drop in lymphocyte count. This inhibition is consistent with published observations of low Earth orbit flown mice and with crewmember blood analyses. In our experiments the cell count suppression was sustained for the entire six-week period of observation and persisted for at least 7 days beyond the period of active hindlimb-unloading. C57Bl/6 mice were also irradiated with 208 MeV Spread Out Bragg Peak (SOBP) protons at the Midwest Proton Radiotherapy Institute at the Indiana University Cyclotron Facility. We found that at 8.5 Gy hindlimb-unloaded mice were significantly more radiation sensitive with 35 lethalities out of 51 mice versus 15 out of 45 control (non-suspended) mice within 30 days of receiving 8.5 Gy of SOBP protons (p =0.001). Both control and hindlimb-unloaded stocktickerCBC analyses of 8.5 Gy proton irradiated and control mice by HEMAVET demonstrated severe reductions in WBC counts (Lymphocytes and PMNs) by day 2 post-irradiation, followed a week to ten days later by reductions in platelets, and then reductions in RBCs about 2 weeks post-irradiation. Recovery of all blood components commenced by three weeks post-irradiation. CBC analyses of 8

Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution

International Nuclear Information System (INIS)

Tulunay, O.; Good, R.A.; Yunis, E.J.

1975-01-01

After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection

Irradiation effects on the tumor and adjacent tissues of brain tumor-bearing mice

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Maki, Yutaka; Tsunemoto, Hiroshi; Koike, Sachiko; Furukawa, Shigeo.

1979-01-01

C 3 H mice aged 56 - 70 days, weighing 27 - 37 g were used throughout this experiment. A transplantable fibrosarcoma arising spontaneously from C 3 H mice was used. For experiment, 10 4 tumor cells suspended in 0.025 ml of saline solution were injected into the cerebral hemisphere by a 26 gauge needle with a micrometer syringe under nembutal anesthesia. Whole brain irradiation was performed at 7 days after injection of the tumor cells and the radiation doses were 2,000 and 20,000 rads, respectively. The feature of x-rays were 200 kVp, 20 mA, 0.5 mm Cu + 0.5 mm Al filtration and TSD 20 cm. The dose-rate was 340 - 360 R/min. The articles of this study were as follows: a) Determination of LD 50 values for the mice, tumor-bearing in the brain or non-tumor-bearing; and b) Observation of clinical features and gross autopsy findings of the mice following irradiation. The LD 50 values for 2,000 rad irradiation in the tumor-bearing or non-tumor-bearing mice were 10.9 and 11.4 days, respectively. LD 50 values of 3.7 days and 4.3 days were the results for the tumor-bearing and non-tumor-bearing mice irradiated by 20,000 rad, respectively. On the other hand, the LD 50 value for the control group, i.e. non-irradiated mice, was 6.7 days. At postmortem examinations, gastrointestinal bleeding was observed frequently in mice bearing tumor in the brain. Whole brain irradiation is effective to prolong the life of tumor-bearing mice. However, in some instances, deaths have occurred earlier in tumor-bearing mice compared to the control group. (author)

Regeneration of CFUs in the marrow of mice exposed to 300 rads after having recovered from 950 rads

International Nuclear Information System (INIS)

Kedo, A.; Barone, J.; Fried, W.

1976-01-01

Exposure to 950 rads 60 Co radiation has been reported to cause long-lasting damage to the hematopoietic stroma (HS), although the size of the CFUs population recovers to pre-irradiation levels. In these studies HS damage was detected only after subcutaneously implanting the femurs of the irradiated mice into syngeneic hosts. To exclude the possibility that what was considered to be HS damage was merely caused by artifacts due to the process of implantation in a new host, the rate of regeneration of CFUs in mice which had recovered from 950 rads prior to receiving 300 rads 60 Co radiation (950 + 300 rads group) was compared with that of mice which received only 300 rads (0 + 300 rads group). The CFUs population in the 950 + 300 rads group grew exponentially for 2 weeks at a rate which did not differ significantly from that of CFUs in the 0 + 300 rads group. However, the rate of CFUs growth reached a plateau before full recovery was achieved in contrast to that in the 0 + 300 rads mice. It was therefore concluded that the incomplete regeneration of CFUs in the marrows of 950 + 300 rads mice was most likely caused by X-irradiation-induced damage to the HS rather than damage to the inherent repopulation potential of the CFUs per se. (author)

Suppression of carcinogenesis in mice by adaptive responses to low dose rate irradiation

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Sakai, Kazuo; Iwasaki, Toshiyasu; Hoshi, Yuko; Nomura, Takaharu; Ina, Yasuhiro; Tanooka, Hiroshi [Central Research Institute of Electric Power Industry, Low Dose Radiation Research Center, Komae, Tokyo (Japan)

2003-07-01

Effects of prolonged low-dose-rate irradiation on the process of carcinogenesis were examined in mice treated with chemical carcinogen or irradiated with high doses of X-rays. Female ICR mice, 5 week-old, 35 in each group, were exposed to gamma-rays from a {sup 137}Cs source in the long-term low dose rate irradiation facility at CRIEPI. The dose rate was 2.6 mGy/hr (A), 0.96 mGy/hr (B), or 0.30 mGy/hr (C). Thirty-five days later, the mice were injected into the groin with 0.5 mg of methylcholanthrene (MC) dissolved in olive oil and irradiation was continued. Cumulative tumor incidences after 216 days following MC injection were 89% in group A, 76% in group B, and 94% in group C. That in non-irradiated control group was 94%. The difference in the tumor incidence between the control and position B was statistically significant, indicating the suppressive effect of the low dose rate irradiation on the process of MC-induced carcinogenesis with an optimum dose rate around 1 mGy/hr. In B6C3F1 mice, although the suppression of tumor incidence was not observed, there was a significant delay in tumor appearance in the irradiated mice between 100-150 days after MC injection. A group of 20 female C57BL/6N mice, 5 weeks old, were exposed to gamma-rays at 0.95 mGy/hr for 5 weeks. Then, they were exposed weekly to 1.8 Gy whole body X-irradiation (300 kVp) for consecutive 4 weeks to induce thymic lymphoma. Another group received only the fractionated irradiation. The first mouse died from thymic lymphoma appeared 89 days after the last irradiation in the group received only the fractionated irradiation, while 110 days in the group combined with the low dose rate irradiation. (author)

Changes of natural killer activity following local 60Co irradiation in intracranial tumor-bearing mice

International Nuclear Information System (INIS)

Otsuka, Shin-ichi; Suda, Kinya; Yamashita, Junkoh; Takeuchi, Juji; Handa, Hajime

1982-01-01

Changes of natural killer activity (NK activity) by local 60 Co irradiation in intracranial tumor-bearing mice were studied by the method of 51 Cr release assay. Local irradiation was administered 10 days after intracranial transplantation of 203-Glioma which had been originally induced by 20-methylcholanthrene in C57BL mice. Irradiation suppressed the growth of tumor and prolonged the mean survival time. The 50% survival time of untreated mice was about 2.5 weeks but that of mice treated by a single dose of 1000 rad and 1500 rad of irradiation was about 4.5 weeks and 6.5 weeks respectively. NK activity of spleen cells in these mice was serially examined. NK activity was gradually increased in mice treated by local irradiation, while it was gradually decreased in mice without treatment. On the other hand, NK activity remained unchanged in non-tumor-bearing control mice. Mice treated with 1000 rad and 1500 rad of irradiation showed 44.0% and 47.6% of % specific 51 Cr release respectively 11 days after irradiation while normal mice showed 18.0%. The increased NK activity after local irradiation suggested that local irradiation might have enhanced the immunological defence mechanisms against the tumor in the tumor-bearing hosts. Some characteristics of effector cells in this assay system were examined. The cytotoxicity of spleen cells was removed by the treatment of anti-BAT serum and complement but was not removed by the treatment of anti-Thy-1.2 serum and complement. Since NK activity reflects the immunological resistance to tumors to some extent, it is felt important to clarify the significance of changes of NK activity in patients with brain tumors in relation to various treatments including surgery, radiotherapy, chemotherapy and immunotherapy in the next step. (author)

Therapeutic effect of recombinant human interleukin-11 and curcumin on jejunal damage in mice after neutron irradiation

International Nuclear Information System (INIS)

Chang Gongmin; Peng Ruiyun; Gao Yabing; Wang Shuiming; Li Yang; Xu Xinping; Wang Lifeng; Dong Ji; Zhao Li

2010-01-01

Objective: To explore the therapeutic effect of recombinant human interleukin (rhIL-11) and curcumin on jejunal damage in mice after neutron irradiation. Methods: 140 male BALB/c mice were randomly divided into 4 groups: 20 mice in healthy control group, 60 mice in mere irradiation group, 30 mice in IL-11 treatment group and 30 mice in curcumin treatment group. The mere irradiation group mice were wholly exposed to 3 Gy neutron irradiation. The treatment groups mice were imtraperitoneally injected with rhIL-11 at the dosage of 500 μg·kg -1 ·d -1 and ourcumin of 200 mg·kg -1 ·/ -1 through enterocoelia once a day for a d after irradiation. The mortality of the mice were observed. The mice in the control and mere irradiation groups were killed 6 h, 1, 3, and 6 d post-irradiation, respectively, and the mice of the 2 treatment groups were killed 3 and 6 d post-irradiation, respectively and the samples of jujunum were colleted. HE staining, argyrophilic of nucleolar organizer staining, Feulgen staining, and image analysis were used to observe the pathology and levels of argyrophilic proteins and DNA. Results: The mice in the mere irradiation group all died at 5 d post-irradiation, while 2 mice in the IL-11 treatment group and 3 in the curcumin group survived. Large area necrosis and exfoliation were found in the intestinal epithelial mucosa of the mere irradiated group mice since 6 h to 3 d after irradiation. Crypt cell regeneration was seen occasionally found 3 days later and much more 5 days later. Crypt cell regeneration was obviously found in the intestinal epithelial mucosa and lots of new villi were observed 5 d after irradiation in both treatment groups, however, the amounts of crypt cells and new villi of the curcumin treatment group were less than those of the IL-11 treatment group. The contents of AgNOR and DNA in the intestinal epithelial cells 5 days after irradiation of the 2 treatment groups were all significantly higher than those of the mere

The role of repopulation in early and late radiation reactions in pig skin

International Nuclear Information System (INIS)

Redpath, J.L.; Peel, D.M.; Dodd, P.; Simmonds, R.H.; Hopewell, J.W.

1984-01-01

The role of repopulation in early and late radiation reactions in pig skin has been assessed by comparing split dose recovery doses (D/sub 2/-D/sub 1/) for a 1-day interval and a 28-day interval. For a 1-day interval, repair of sublethal damage is the major contribution to any recovery observed, whereas for a 28-day interval, repopulation may also play a role. The early reaction studied was moist desquamation and the late reactions studied were a later dermal erythema and necrosis. The data show that over a 28-day interval, repopulation contributes -- 7.0 Gy to a total D/sub 2/-D/sub 1/, of --14.0 Gy for the early moist desquamation (epidermal) reaction. Data for the role of repopulation in the late (dermal) reactions are also presented

Survival of Lymphatic Cells after X-Irradiation in Mice

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Vos, O. [Medical Biological Laboratory, National Defense Research Organization TNO, Ruswuk, Z.H. (Netherlands)

1967-07-15

Lymphatic tissues are generally classified among the most radiosensitive tissues of the body. The main reason for this is that histologically extensive destruction is found within a few hours after irradiation. We tried to estimate the degree of cellular degeneration by making cell suspensions from lymph nodes and thymus of mice at different times after X-irradiation with 800 R or at 24 h after radiation with different doses. The numbers of normal viable cells we obtained were expressed as percentages of the cells recovered from unirradiated control mice.

The analysis of the defense mechanism against indigenous bacterial translocation in X-irradiated mice

International Nuclear Information System (INIS)

Kobayashi, Toshiya; Ohmori, Toshihiro; Yanai, Minoru; Kawanishi, Gosei; Mitsuyama, Masao; Nomoto, Kikuo.

1991-01-01

The defense mechanism against indigenous bacterial translocation was studied using a model of endogenous infection in X-irradiated mice. All mice irradiated with 9 Gy died from day 8 to day 15 after irradiation. The death of mice was observed in parallel with the appearance of bacteria from day 7 in various organs, and the causative agent was identified to be Escherichia coli, an indigenous bacterium translocating from the intestine. Decrease in the number of blood leukocytes, peritoneal cells and lymphocytes in Peyer's patches or mesenteric lymph nodes was observed as early as 1 day after irradiation with 6 or 9 Gy. The mitogenic response of lymphocytes from various lymphoid tissues was severely affected as well. The impairment of these parameters for host defense reached the peak 3 days after irradiation and there was no recovery. However, in vivo bacterial activity of Kupffer cells in mice irradiated with 9 Gy was maintained in a normal level for a longer period. It was suggested that Kupffer cells play an important role in the defense against indigenous bacteria translocating from the intenstine in mice. (author)

Therapeutic effects of gingerol on hematopoietic and antioxidative damage of 60Co γ-rays irradiated mice

International Nuclear Information System (INIS)

Geng Yanyan; Xie Zhenfei; Zhou Yu; Zeng Xianyin

2012-01-01

18 female Kunming mice were chosen and randomly divided into three groups, and the therapeutic effects of gingerol on hemopoietic and antioxidative system in liver of 60 Co γ-rays irradiated mice were developed in this study. Control group was given distilled water intragastrically once a day for five days. Mice in the irradiated group and irradiated + gingerol group were both irradiated at 3 Gy of 60 Co γ-rays and were given distilled water and gingerol intragastrically within 30 min after irradiation respectively, once a day for five days. The mice were sacrificed and sampled in 48 hours after intragastric administration. Compared with control group, the relative spleen index and WBC numbers significantly decreased (P 60 Co γ-rays irradiated mice. (authors)

Long-term effect of whole-body X-irradiation on cell-mediated immune reaction in mice

International Nuclear Information System (INIS)

Norimura, Toshiyuki; Tsuchiya, Takehiko

1989-01-01

Age-related change in immunological activity was examined at 10 to 91 weeks following whole-body irradiation by determining the specific anti-tumor cell-mediated immunity in host mice induced and/or enhanced by local irradiation to transplanted tumor. Median survival time of the non-irradiated C3H/He female mice was 98.6 weeks while the median life-span of the mice exposed to two and four Gy of 250 kVp X-rays at the age of 10-12 weeks was shortened by 14.9 and 23.4 weeks, respectively. The rate of tumor reduction within two weeks after local irradiation to tumor and the growth inhibitory activitiy of spleen cells from tumor irradiated mice were reduced in a dose-dependent manner when assessed 10 weeks after whole-body irradiation, but recovered to the near-complete level of the non-irradiated controls within a few months, then gradually decreased with normal aging. These results suggest that the age-dependent decline of this immunological activity apears earlier in the irradiated mice as a result of whole-body X-irradiation at a young age, suggesting accelerated aging of the immune system. (author)

Pathomorphology of spleen lymphocyte apoptosis in large dose 60Co γ-irradiated mice

International Nuclear Information System (INIS)

Gao Linlu; Cui Yufang; Yang Hong; Xia Guowei; Peng Ruiyun; Gao Yabing; Wang Dewen

2000-01-01

Objective: The aim of the authors was to investigate the pathomorphology changes of spleen lymphocyte apoptosis after 60 Co γ-irradiation. Methods: The mice were irradiated with 6, 9, 12, 15 and 20 Gy of 60 Co γ-rays. At different times after irradiation, the mice were sacrificed and the pathological changes of spleen lymphocyte were observed by light and transmission electron microscopies. Results: Spleen lymphocyte decreased evidently and the peak of apoptosis in spleen lymphocyte was dependent on radiation dose and the time after irradiation. Conclusion: After γ-irradiation with large doses, pathological changes of spleen lymphocyte apoptosis in mice can be divided into obviously different stages. The main causes of death of spleen lymphocytes are different in different dose groups

Kinetics of Hesperetin for Liver Fortification in gamma-Irradiated Mice

International Nuclear Information System (INIS)

Tawfik, S.S.

2011-01-01

Hesperetin (3',5,7-trihydroxy-4'-methoxyflavonone), the aglycone of the flavanone glycosides hesperidin, exerts pharmacological properties such as antioxidation, anti-inflammation, blood lipid and cholesterol lowering is effectively used as a supplemental agent in the treatment protocols of complementary settings. Four groups were prepared: Control group: received 0.5 ml normal saline for 7 days. Hesperetin group: Mice received 7 doses of hesperetin injections (100 mg/ kg body wt/ day). Irradiated group: Mice submitted to total body irradiation with 4 Gy gamma-rays. Protected group (Hesperetin plus irradiation): Mice received hesperetin for 7 days and then submitted to 4 Gy of gamma-rays. The mice were sacrificed at 24 h, 1 week and 2 weeks after the end of the experimental treatments. Irradiated mice exhibited significant hyperglycaemia and augmented hepatic glycogen after the first day and 1 week but significant hypoglycemia and reducing hepatic glycogen after 2 weeks. Also, they exhibited significant increased serum total cholesterol (TC) and triacylglycerols (TG) and decreased hepatic TC and TG after 1 and 2 weeks. This treatment also resulted in a significant dropped in hepatic glucokinase (GK), glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) activities after 1 and 2 weeks. Hesperetin injections modulated the serum glucose and hepatic glycogen, adjusted TC and TG in both serum and liver and ameliorated the lessening in hepatic GK, G6P and PEPCK. The attending results demonstrated that hesperetn treatment modulated the biochemical symptoms of radiation disorders in mice. In conclusion, administration of hesperetin may have a useful role in modulating oxidative stress induced by exposure to gamma-radiation by improving the natural antioxidant mechanism and fortification liver functions

Development of Schistosoma incognitum in mice upon intraperitoneal inoculation with irradiated schistosomula

International Nuclear Information System (INIS)

Bhilegaonkar, N.G.; Sahasrabudhe, V.K.

1987-01-01

As a prelude to the study of the immunizing potential of gamma-irradiated Schistosoma incognitum schistosomula, experiments were conducted to study the effect of different doses of gamma irradiation (1,3,5 and 10 kr) on the development and survival of S. incognitum in mice, and its attendant pathology. The present experiments suggested that 3 and 5 kr irradiation doses can be safely used for irradiating schistosomula for immunization experiments in mice as the worms will not mature and therefore no harm will be caused which is mainly due to the eggs. (author). 7 refs

Whole-body X-irradiation of mice accelerates polyploidization of hepatocytes

International Nuclear Information System (INIS)

Shima, A.; Egami, N.

1985-01-01

Male C57BL/6 mice were whole-body irradiated with 4.75 gy of X-rays at the age of 2 months and killed at 2, 6, 12 and 19 months after irradiation. The percentage survival began to decline earlier and faster in the irradiated group than the controls up to 19 months after exposure when the study was terminated. The nuclear DNA content of individual hepatocytes was measured by a Feulgen-DNA microfluorometric method, and hepatocytes were classified into various ploidy classes. In the irradiated mice, the degree of polyploidization was significantly higher than the controls by 2 months after exposure and steadily increased up to 6 months after exposure. Thereafter, however, a slow return to the control level was found up to 19 months after irradiation. These results appear to support a hypothesis that radiation accelerates the ageing process as judged from hepatocyte polyploidization. (author)

Recovery Effect and Life Prolong Effect of Long Term Low-Dose Rate Irradiation on Type II Diabetes Model Mice

International Nuclear Information System (INIS)

Nomura, T.; Makino, N.; Oda, T.; Suzuki, I.; Sakai, K

2004-01-01

The effects of low-dose rate gamma-irradiation were investigated on model mice for type II diabetes mellitus, C57BL/KsJ-db/db. The mice develop the type II diabetes by 10 weeks of age due to obesity and are characterized by hyperinsulinemia. Female 10-week old mice, a group of 12 mice, were irradiated at 0.65 mGy/hr from 137-Cs (370 GBq). The urine glucose levels of all of the mice were strongly positive at the beginning of the irradiation. In the irradiated group, the decrease in the glucose level was observed in 3 mice. Such recovery from the diabetes was never observed in 12 mice of non-irradiated control group. There is no systematic difference in the change of body weight, food assumption, and amount of drinking water, between the irradiated group and the non-irradiated group or between the recovered mice and the non-recovered mice. The survival was better in the irradiated group: the surviving fraction at the age of 90 weeks was 75% in the irradiated group, while 40% in the non-irradiated. Marked difference was also observed in the appearance of the coat hair, skin, and tail; better condition was kept in the irradiated group. In the irradiated mice mortality was delayed and the healthy appearance was prolonged in the irradiated mice by about 20 ? 30 weeks compared with the non-irradiated mice. These results suggest that the low-dose irradiation modified the condition of the diabetic mice, which lead not only to the recovery of the diabetes, but also to the suppression of the aging process. (Author)

Apparent failure of thymic epithelium transplants to alter the course of autoimmune disease in NZB/W mice

International Nuclear Information System (INIS)

Morrow, W.J.W.; Nayak, R.C.; Cooke, A.; Roitt, I.M.

1982-01-01

Thymic epithelium from neonatal DBA/2 mice (H-2sup(d)) was placed under the kidney capsule of 10- to 12-wk-old female NZB/W mice (H-2sup(d/z)). Donor epithelium, equivalent to 1-2 lobes of neonatal thymus, was either irradiated (1300 rad.) or cultured for 7 days in order to minimise host-versus-graft reactions. Histological examination showed that the epithelium repopulated and remained in place until the end of the experiment, with no sign of rejection. Despite this, the treated animals lived no longer than the untreated or sham operated controls. Levels of anti-nuclear antibody and serum IgM (normally highly elevated in these animals) were not significantly different in any group. (Auth.)

Radioprotective effect of colony-stimulating factor on mice irradiated with 60Co γ-rays

International Nuclear Information System (INIS)

Zhang Junning; Wang Tao; Xu Changshao; Wang Hongyun

1995-01-01

Adult male mice were irradiated with γ-rays 6 Gy once or 3 Gy three times in 7 days and intraperitoneally injected with colony-stimulating factor (CSF) in high doses or low doses. Mice of the control group were injected with normal saline only. Within 30 days after irradiation, the survival rate of mice irradiated with 6 Gy γ-rays once and treated with high dose CSF was 9/25, while that in the control group was 2/25. The survival rate of mice irradiated with 3 Gy three times and treated with high dose CSF was 10/13, while that in the control group was 4/13. Moreover, the survival times of both irradiated groups treated with high dose CSF were much longer than the control groups (p<0.01). This experiment also showed that CSF could reduce the lowering of peripheral blood white blood cell counts and promote their recovery. The number of CFU-S in mice treated with CSF was much higher (23.8 +- 4.82) than in the control group (9.4 +- 4.39) (p<0.01). Therefore, CSF could recover and reconstruct the hematopoietic function of bone marrow, and prolong the survival of irradiated mice

Repopulation response of mouse oral mucosa during unconventional radiotherapy protocols

International Nuclear Information System (INIS)

Doerr, Wolfgang; Weber-Frisch, Marion

1995-01-01

Repopulation in mouse tongue epithelium was determined during unconventional fractionation schedules, i.e., hyperfractionation (2 x 1.5 and 2 x 1.75 Gy/day) and accelerated treatment (2 x 3 Gy/day). The residual tolerance of the epithelium at defined days of the fractionated treatment was tested by graded single test doses (top-up design). The dose required to induce complete epithelial denudation in 50% of the animals (ED50) was used to calculate the number of fractions repopulated during the preceding treatment. After the first week of hyperfractionation, tolerance was reduced compared to untreated epithelium. However, subsequently no further change was observed, indicating complete compensation of the weekly dose with all doses per fraction used. Epithelial cell density, defined by histological examination in additional experiments, in all fractionation arms decreased similarly by ∼40% during the first week and remained constant at 60-80% in the subsequent 2 weeks. During accelerated fractionation, the residual mucosal tolerance decreased continuously with treatment time and resulted in epithelial denudation after 12 fractions. However, a substantial repopulation effect was observed, compensating 1.5 fractions by day 2, and 5 fractions by day 5, respectively. After cessation of the therapy the repopulation rate clearly decelerated to compensate a dose equivalent to about 0.5 fractions per day. Cell density decreased linearly during the treatment with 5, 10 or 12 fractions at a rate close to normal cell loss. Marked cell production, dependent on the total fractionated dose, was seen from one day after the last fraction in each experimental arm. These results indicate that maximum stem cell repopulation occurs predominantly during treatment, while major production of differentiating cells takes place in treatment splits

Types and rate of cataract development in mice irradiated at different ages

International Nuclear Information System (INIS)

Gajewski, A.K.; Majewska, K.; Slowikowska, M.G.; Chomiczewski, K.; Kulig, A.

1977-01-01

The effect of age on the development of radiation cataract has been investigated in an inbred A strain of mice and, as a result, the patterns of age dependence and senile mice cataract development were obtained. In general, the lenses of mice 1 to 3 days old were the most sensitive to radiation; the maximum resistance was noted in 5-day-old mice, and from this age up to 3 to 7 weeks of life there was a period of increasing sensitivity. In older animals the lens sensitivity tends to level off. The early stages of cataract occurred in all irradiated groups at a younger age than in the control group, but the late stages occurred in irradiated groups at the same age as the senile cataract occurred in the control group. Two types of cataract were observed. One was typical for young irradiated mice 1 to 5 days of age and the other was typical for all remaining irradiated groups and for a control group. Also, an attempt was made to correlate the obtained results with the cell kinetics in normal lens epithelium

Gamma-irradiated scrub typhus immunogens: development of cell-mediated immunity after vaccination of inbred mice

International Nuclear Information System (INIS)

Jerrells, T.R.; Palmer, B.A.; Osterman, J.V.

1983-01-01

Mice immunized with three injections of gamma-irradiated Karp strain of Rickettsia tsutsugamushi were evaluated for the presence of cell-mediated immunity by using delayed-type hypersensitivity, antigen-induced lymphocyte proliferation, and antigen-induced lymphokine production. These animals also were evaluated for levels of circulating antibody after immunization as well as for the presence of rickettsemia after intraperitoneal challenge with viable Karp rickettsiae. After immunization with irradiated Karp rickettsiae, a demonstrable cell-mediated immunity was present as evidenced by delayed-type hypersensitivity responsiveness, lymphocyte proliferation, and production of migration inhibition factor and interferon by immune spleen lymphocytes. Also, a reduction in circulating rickettsiae was seen in mice immunized with irradiated rickettsiae after challenge with 1,000 50% mouse lethal doses of viable, homologous rickettsiae. All responses except antibody titer and reduction of rickettsemia were similar to the responses noted in mice immunized with viable organisms. Antibody levels were lower in mice immunized with irradiated rickettsiae than in mice immunized with viable rickettsiae. Furthermore, mice that were immunized with viable rickettsiae demonstrated markedly lower levels of rickettsemia after intraperitoneal challenge compared with either mice immunized with irradiated rickettsiae or nonimmunized mice

Effect of combination therapy with irradiation and ACNU on rectal cancer in mice

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Masahiko; Nakajima, Atsushi; Kato, Koichiro; Eiraku, Hitoshi (Tokyo Medical Coll. (Japan))

1992-03-01

Colon 26, a transplantable strain of colon cancer, was implanted in BALB/C mice, and the effect of combination therapy with irradiation and ACNU on the mice was studied. Regional irradiation with 9 MeV electron beams was administered once without anesthetization, and ACNU was injected intraperitoneally. The 102 mice used as subjects were divided into 6 groups: nontreated group, 3 Gy irradiation group, 9 Gy irradiation group, 20 mg/kg ACNU group, 40 mg/kg ACNU group, and 3 Gy irradiation + 20 mg/kg ACNU group. Antitumor effects were evaluated based on survival time and inhibition of tumor volume growth, which were calculated from mean days of survival, Kaplan-Meier survival rate curves, and tumor volume growth curves, and the results were compared among these 6 groups. In addition, pathological and cytological studies were performed. As a result, antitumor effect was found to be significantly remarkable in the group receiving the combination of irradiation and ACNU compared to any other group given either irradiation or ACNU alone, suggesting that the antitumor effect of irradiation was potentiated by ACNU. (author).

Radioprotection conferred by dextran sulfate given before irradiation in mice

International Nuclear Information System (INIS)

Ross, W.M.; Peeke, J.

1986-01-01

Dextran sulfate (DS) has been observed to cause mobilization (fivefold) of hemopoietic stem cells (HSC) and leukocytes, primarily lymphocytes, into the peripheral blood of mice within 2-3 h after intraperitoneal (i.p.) injection. This effect was dose dependent and was prolonged for several hours when the high-molecular-weight version DS500 (500,000 daltons) was used. When DS500 was given 1-3 days before irradiation, hemopoietic recovery was markedly enhanced. Postirradiation injection was ineffective. By ten days after irradiation (7.0 Gy), the number of endogenous spleen colonies (CFUs) and the splenic mass were much larger if DS pretreatment had been given. This effect was dependent on the dose of DS500 and on the time administered, 60 mg/kg producing a maximal effect when given three days before irradiation. DS500 caused a transient anaphylactoid shock, however, in most mice--mild at low doses but potentially lethal at doses above 40 mg/kg (10% mortality within 1-3 days after 60 mg/kg). The following results were obtained with 50 mg/kg, a compromise dose causing minimal mortality (3%) given three days before irradiation. Reticulocyte reappearance was earlier in irradiated mice given DS500, indicating earlier erythropoietic recovery. Some of these reticulocytes were resistant to lysing agents, so their appearance could be detected using the Coulter electronic cell counter, as well as in stained blood smears. The 30-day mortality due to bone marrow failure after irradiation was significantly decreased in DS-treated mice below 9.5 Gy, and the LD50/30 was increased by 0.5 Gy. This study shows that dextran sulfate exerts a radioprotective influence on the hemopoietic system and hence survival when administered prophylactically

Effect of single and fractionated x-irradiation on maze learning ability of mice

International Nuclear Information System (INIS)

Aoyama, Takashi; Norimura, Toshiyuki; Nakamura, Takeshi; Yoshikawa, Isao

1976-01-01

Fifty-six-day-old male ddk mice at the starting of the investigation were used as subjects through the experiment for 64 weeks. After 15 days' preliminary training, and 16 times of weekly trial training using complete maze, 15 mice received a single 224 rads of x-rays (S group), another 15 mice received two 112 rads spaced two weeks apart (F group) and another 15 mice were sham-irradiated (Control group). Then those mice were tested on the multiple T-maze with nine-choice points and change of performance was observed in terms of errorchoices by giving one test trial a week. We introduced the concept of ''confusional trials'' as an index for surmising to what extent mice failed to exhibit good maze learning habits. In the results, the F group showed significantly worse performance than the two other groups at early stages, opposite to it the S group exhibited the same, but at late stages after irradiation. The worse performance of F group should be considered to be due to the psychological after-effect to fractionated irradiation and that for S group could be assumed to be due to the acceleration of aging by the irradiation. (auth.)

Late vascular effects in irradiated mice brain

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Maki, Yutaka; Phillips, T.L.

1982-01-01

The whole brains of mice were irradiated with 250 kVp X-ray at 120 rad min -1 (1.6 mm Cu HVL, TSD 50 cm) and a histological study was done. The dose range of X-irradiation was from 1300 to 2500 rads. i.e., 1300, 1500, 1750, 2000, and 2500 rads. In the microscopic examination, the mice were killed at the regular postirradiation intervals of between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. A histological examination was performed by a morphometric estimation of vascular lesion in which the degree of the damage to the arterial system was scored through whole serial brain sections. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectatic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large artery were observed. Incidence of the fibrinoid necrosis increased dose dependently between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 - 87 weeks and can be used to quantify the vessel injury and a fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis. (author)

The HYP-RT Hypoxic Tumour Radiotherapy Algorithm and Accelerated Repopulation Dose per Fraction Study

Directory of Open Access Journals (Sweden)

W. M. Harriss-Phillips

2012-01-01

Full Text Available The HYP-RT model simulates hypoxic tumour growth for head and neck cancer as well as radiotherapy and the effects of accelerated repopulation and reoxygenation. This report outlines algorithm design, parameterisation and the impact of accelerated repopulation on the increase in dose/fraction needed to control the extra cell propagation during accelerated repopulation. Cell kill probabilities are based on Linear Quadratic theory, with oxygenation levels and proliferative capacity influencing cell death. Hypoxia is modelled through oxygen level allocation based on pO2 histograms. Accelerated repopulation is modelled by increasing the stem cell symmetrical division probability, while the process of reoxygenation utilises randomised pO2 increments to the cell population after each treatment fraction. Propagation of 108 tumour cells requires 5–30 minutes. Controlling the extra cell growth induced by accelerated repopulation requires a dose/fraction increase of 0.5–1.0 Gy, in agreement with published reports. The average reoxygenation pO2 increment of 3 mmHg per fraction results in full tumour reoxygenation after shrinkage to approximately 1 mm. HYP-RT is a computationally efficient model simulating tumour growth and radiotherapy, incorporating accelerated repopulation and reoxygenation. It may be used to explore cell kill outcomes during radiotherapy while varying key radiobiological and tumour specific parameters, such as the degree of hypoxia.

Neonatal irradiation sensitizes mice to delayed pulmonary challenge.

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Johnston, Carl J; Manning, Casey M; Rangel-Moreno, Javier; Randall, Troy D; Hernady, Eric; Finkelstein, Jacob N; Williams, Jacqueline P

2013-04-01

Significant differences exist between the physiology of the immature, neonatal lung compared to that of the adult lung that may affect acute and late responses to irradiation. Identifying these differences is critical to developing successful mitigation strategies for this special population. Our current hypothesis proposes that irradiation during the neonatal period will alter developmental processes, resulting in long-term consequences, including altered susceptibility to challenge with respiratory pathogens. C57BL/6J mice, 4 days of age, received 5 Gy whole-body irradiation. At subsequent time points (12, 26 and 46 weeks postirradiation), mice were intranasally infected with 120 HAU of influenza A virus. Fourteen days later, mice were sacrificed and tissues were collected for examination. Morbidity was monitored following changes in body weight and survival. The magnitude of the pulmonary response was determined by bronchoalveolar lavage, histological examination and gene expression of epithelial and inflammatory markers. Viral clearance was assessed 7 days post-influenza infection. Following influenza infection, irradiated animals that were infected at 26 and 46 weeks postirradiation lost significantly more weight and demonstrated reduced survival compared with those infected at 12 weeks postirradiation, with the greatest deleterious effect seen at the late time point. The results of these experiments suggest that radiation injury during early life may affect the lung's response to a subsequent pathogenic aerial challenge, possibly through a chronic and progressive defect in the immune system. This finding may have implications for the development of countermeasures in the context of systemic radiation exposure.

Effects of mecobalamin on testicular dysfunction induced by X-ray irradiation in mice

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Oshio, Shigeru; Yazaki, Tsunetada; Umeda, Takashi; Ozaki, Satoru; Ohkawa, Isao; Tajima, Tetsuya; Yamada, Takeshi; Mohri, Hideo.

1991-01-01

Experimental testicular dysfunction was produced by X-ray irradiation to the testes in mice. Mecobalamin (CH 3 -B 12 ) was orally administered at a daily dose of 0.01, 0.1 or 1 mg/kg six times a week for 8 weeks from the next day after the irradiation. The control mice received physiological saline in the same manner. On 4th- and 6th-week after the irradiation, the weights of testes and epididymides were decreased, although those of the body and accessory sex glands (seminal vesicle, coagulating gland and prostate) were nearly equal to those of non-irradiated mice. At the same time, the diameter of seminiferous tubules decreased and sperm parameters (sperm count, sperm motility and sperm abnormality) deteriorated. When CH 3 -B 12 (1 mg/kg) was administered, the diameter of seminiferous tubules increased and sperm parameters improved as compared to those of the control. The results indicate that CH 3 -B 12 improved the experimental testicular dysfunction in mice induced by the irradiation. These results suggest that CH 3 -B 12 might accelerate testicular function. (author)

Bone marrow function. I. Peripheral T cells are responsible for the increased auto-antiidiotype response of older mice

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Kim, Y.T.; Goidl, E.A.; Samarut, C.; Weksler, M.E.; Thorbecke, G.J.; Siskind, G.W.

1985-01-01

After immunization with trinitrophenyl (TNP)-Ficoll, mice produced both anti-TNP antibodies and auto-anti-idiotype (auto-anti-Id) antibodies specific for the anti-TNP antibody. Older animals produced more auto-anti-Id than did young animals. When mice were exposed to a normally lethal dose of irradiation while their bone marrow (BM) was partially shielded, they survived and slowly (6 wk) regained immune function, as indicated by the number of nucleated cells in their spleen and the in vitro primary plaque-forming cell (PFC) response of their spleen cells to TNP-treated aminoethylated polyacrylamide beads. Recovery is presumably the result of repopulation of the peripheral lymphoid system by cells originating in the BM. By enzyme-linked immunosorbent assay (ELISA), and by hapten-augmentable PFC assay, the authors show that, after recovery from irradiation with their BM shielded, old animals produce low auto-anti-Id responses, like those of young animals. The transfer of splenic T cells into mice irradiated with their BM shielded provided evidence that the magnitude of the auto-anti-Id response is controlled by the peripheral T cells. Thus, mice that received splenic T cells from aged donors produced high levels of auto-anti-Id while those that received splenic T cells from young donors produce low levels of auto-anti-Id

Dominant lethal mutations research in mice fed with irradiated black beams

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Andrade, Z.P.

1982-01-01

To evaluate the potential mutagenic effects of irradiated black beans (Phaseolus vulgaris) with conservation purpose, in germ cells of mice, dominant lethal assay were employed. Three groups of albino swiss male mice (S W-55) were fed with a normal ration, or unirradiated or irradiated (0,2; 0,5; 1; 5; 10; 15 e 20 KGy) test diets for eight weeks. After the feeding period the males were mated with groups of untreated females mice for four consecutive weeks. Numbers of pregnancy rates females were observed. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. (author)

The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice

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Allam, Ayman; Perez, Luis A.; Huang, Peigen; Taghian, Alphonse; Azinovic, Ignacio; Freeman, Jill; Duffy, Michael; Efird, Jimmy; Suit, Herman D.

1995-01-01

Purpose: To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (T pot ) of this tumor to the effective doubling time (T eff ) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. Methods and Materials: The TCP was assessed using the TCD 50 value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7-8 mm. The mean interfraction intervals were from 8-24 h. The T pot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to T eff . Results: The TCD 50 values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD 50 values was significant (p pot (2.4 days) was longer than the calculated T eff in groups 2 and 3 (1.35 days). Conclusion: Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an accelerated repopulation of tumor clonogens. The pretreatment T pot of this tumor model does not reflect the actual doubling of the clonogens in a protracted regimen

Attenuated lung fibrosis in interleukin 6 knock-out mice after C-ion irradiation to lung

International Nuclear Information System (INIS)

Saito-Fujita, Tomoko; Iwakawa, Mayumi; Nakamura, Etsuko; Nakawatari, Miyako; Fujita, Hidetoshi; Moritake, Takashi; Imai, Takashi

2011-01-01

There is a great deal of evidence that a cyclic cascade of inflammatory cytokines, together with the activation of macrophages, is initiated very early after irradiation to develop lung fibrosis in a late phase. To understand the persistent effects of cytokines, the cytokine gene of knock out or transgenic mouse is one of the useful tools. In this study, we evaluated a role of a key molecule, interleukin-6 (IL-6), in the late-phase inflammatory response and subsequent fibrotic changes after irradiation using wild-type (WT) and IL-6 knock out (IL-6 KO) mice. The mice underwent thoracic irradiation with 10 Gy of C-ion beam or sham-irradiation and were examined by histology. Immunoreactivity for IL-6 was induced at the site of bronchiolar epithelium, in pneumocytes and in monocytes by C-ion irradiation. At 24 weeks after irradiation, the infiltration of macrophages, detected by positive immunohistological staining with Mac3 antibody, was observed in alveolar spaces both in WT and IL-6 KO mice. The thickening of bronchiolar and alveolar walls exhibited in WT mice, but not KO mice, and fibrotic changes detected by Masson-Trichrome staining, were observed only in the lungs of WT mice, while it was attenuated in IL-6 KO mice. These results indicated that IL-6 might not be essential for activating macrophages in the late phase, but plays an important role for fibrotic changes of the alveolar wall after irradiation. (author)

[Protective Effect of S-isopentenyl-L-cysteine against DNA Damage in Irradiated Mice].

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Zheng, Qi-sheng; Yu, Guang-yun; He, Xin; Jiang, Ming; Chu, Xiao-fei; Zhao, Shu-yi; Fan, Sai-jun; Liu, Pei-xun

2015-10-01

To evaluate the protective effect of S-isopentenyl-L-cysteine,a new cysteine derivative,on DNA damage induced by radiation by using acute radiation injury animal models. Forty ICR mice were randomly divided into five groups:the control group,1.0Gy gamma irradiation group,1.0Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,7.2Gy gamma irradiation group,and 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,with 8 mice in each group.The comet assay and bone marrow polychromatic micronucleus experiments were performed to evaluate the double-strand DNA breaks in ICR mice exposed to 1.0 and 7.2Gy gamma-ray, respectively. The tail DNA percentage,tail length,tail moment,and olive tail moment of peripheral blood lymphocytes in 7.2Gy gamma irradiation group were significantly higher than that of the control group (PL-cysteine group was significantly less than that of 7.2Gy gamma irradiation group (PL-cysteine before irradiation,the micronucleus rate of ICR mice exposed to 1.0 and 7.2Gy gamma-ray decreased from (39.5000 ± 3.3141)‰ to (28.1667±4.1345)‰ (P=0.033) and from (76.5000 ± 4.6242)‰ to (22.8333 ± 3.6553)‰(P=0.000),respectively. The bone marrow polychromatic micronucleus experiment indicated that the value of polychromatic erythrocyte (PCE)/normochromatic erythrocyte(NCE) of ICR mice exposed to 1.0 and 7.2Gy gamma-ray was less than the control group(PL-cysteine before irradiation was significantly higher than the corresponding groups (PL-cysteine has a good protective effect against DNA damage induced by radiation.

Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice.

Science.gov (United States)

Yang, Miyoung; Kim, Hwanseong; Kim, Juhwan; Kim, Sung-Ho; Kim, Jong-Choon; Bae, Chun-Sik; Kim, Joong-Sun; Shin, Taekyun; Moon, Changjong

2012-03-01

Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.

Pluripotent stem cells with normal or reduced self renewal survive lethal irradiation

International Nuclear Information System (INIS)

Brecher, G.; Neben, S.; Yee, M.; Bullis, J.; Cronkite, E.P.

1988-01-01

Transfusion with 10,000 or 20,000 marrow cells resulted in 30+ days survival of 15%-50% of mice exposed to an Ld90 or LD100 or radiation. The use of congenic mice with alloenzyme markers permitted the identification of host and donor cells in the peripheral blood of transfused animals. Donor cells were present initially in all hosts. Between 55% and 92% of the animals became 100% host type by 12-24 weeks after transfusion in three separate experiments. To explore whether the temporary repopulation by donor cells was due to short-lived stem cells, the marrows of several primary hosts were transfused into secondary, lethally irradiated hosts. Some of the retransplanted primary donor and host cells persisted only temporarily. It is suggested that some of the donor stem cells in both the primary and secondary hosts had an intrinsically shortened life span

Cross-immunity between syngeneic tumors in mice immunized with gamma-irradiated ascites tumors

International Nuclear Information System (INIS)

Kudo, Hajime; Waga, Takashi; Sato, Tatsusuke; Ogasawara, Masamichi; Ito, Izumi

1980-01-01

C3H/He mice immunized repeatedly with irradiated (13,000 rads 60 Co) MM46 or MM48, both transplantable ascites mammary carcinomas of the same strain, were subcutaneously challenged with the identical or the different tumor. In mice immunized with irradiated MM46, the growth of challenges of not only MM46 but also MM48 was inhibited. On the other hand, in mice immunized with irradiated MM48, the growth of challenges of MM48 was inhibited, but the inhibition of the growth of MM46 was not observed. Cross-immunity, therefore, was shown by immunization with MM46 but not with MM48. These findings were considered to indicate that MM46 expressed cross-immunity against MM48 because of its high resistance to the irradiation, and that MM48 did not show cross-immunity to MM46 because of its low resistance to the irradiation. (author)

Stimulatory effect of aminoethylisothiuronium on the immune response and interferogenesis in irradiated mice

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Zheleznikova, G.F.; Ogurtsov, R.P.; Stepanov, A.N. (Tsentral' nyj Nauchno-Issledovatel' skij Rentgeno-Radiologicheskij Inst., Leningrad (USSR))

Aminoethylisothiuronium (AET) stimulated the formation of antibodies against sheep erythrocytes, not against E. coli, in X-irradiated (4 Gy) mice. The serum containing AET-induced interferon had the same effect. AET also promoted the rejection of the allogenic skin graft in mice irradiated with the same dose. In addition, AET and cystaphos stimulated the induction of interferon by the Newcastle disease virus in mice exposed to doses of 4, 5 or 6 Gy.

Time factor and repopulation during fractionated radiotherapy. Comparison between two xenografted human squamous cell carcinoma

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Hesselmann, S.; Horn, K.; Koenemann, S.; Schuck, A.; Willich, N.; Lindel, K.; Ruebe, C.

2003-01-01

Background: A series of experiments were performed to determine the local tumour control of two human squamous cell carcinoma lines in nude mice. An accelerated-fractionated radiation therapy regime is compared to a conventional-fractionated therapy regime. Material and Methods: KB is a well established human nasopharyngeal squamous cell carcinoma line (ATCC CCL 17). In nude mice KB grows as an low differentiated carcinoma. PEC MB is an undifferentiated squamous cell carcinoma of the maxillary sinus, which was successfully established in nude mice by our group 1993. Both tumors were serially passaged in nude mice. Local irradiation was given without anaesthesia under ambient conditions to air breathing animals using 18 MeV electrons of an linear accelerator (Mevatron 77, Siemens, Munich). Each dose level group consists of six to eight animals. The radiation treatments were given in ten equals fractions using graded dose levels of 2, 3, 4.5, 6 and 8 Gy. The interfraction time interval was 6 hours in the accelerated-fractionated group and 24 hours in the conventional-fractionated group. In the conventional-fractionated group a therapy break was given after 5 fractions for 72 h. The endpoint of the experiments was the dose, which was necessary to control 50% of the tumors (TCD 50 ). The TCD 50 values were calculated after 60 days (Tables 1a and 1b). Results: The experiments show, that with increasing overall treatment time of 8 3/4 days using the same number of fractions under ambient conditions the tumor control dose of the tumor KB increases from 36.3 Gy (95% CI 30.9.. 42.7) to 44.3 Gy (38.3.. 51.2). For the tumor PEC MB the tumor control dose increases from 39.5 Gy (33.4.. 46.7) to 45.5 Gy (37.0.. 56.0). Conclusion: This observed increase of the dose necessary to control the squamous cell carcinoma KB and PEC MB can be caused by repopulation of clonogenic tumors cells, however, other mechanism such as an increasing fraction of hypoxic tumor cells can not be ruled

: acquired resistance in mice by implantation of young irradiated worms into the portal system

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Paulo Marcos Z. Coelho

1989-02-01

Full Text Available In two distinct experiments, immature S. mansoni worms (LE strain, Belo Horizonte, Brazil, aged 20 days, obtained from the portal system of white outbred mice, were irradiated with 14 and 4 Krad, respectively. Afterwards, the worms were directly inoculated into the portal vein of normal mice. Inoculation was performed with 20 irradiated worms per animal. Fifty days after inoculation, the mice that received 4 and 14 Krad-irradiated worms and their respective controls were infected with S. mansoni cercariae (LE strain, by transcutaneous route. Twenty days after this challenge infection, the animals were sacrificed and perfused for mature irradiated (90-day-old and immature (20-day-old worm counts. Analysis of the results showed that statistically significant protection against cercariae occurred in both groups with irradiated worms.

Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice.

Directory of Open Access Journals (Sweden)

Junye Zhang

Full Text Available One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO to restore the secretory function of radiation-damaged salivary glands in mice.DFO (50 mg/kg/d was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy of submandibular glands. The total 55 mice were randomly divided into: (1 Normal group: mice received no treatment (n = 5; (2 Irradiation group (IR: mice only received irradiation (n = 5; (3 Pre-DFO group (D+IR (n = 10; (4 Pre+Post DFO group (D+IR+D (n = 10; (5 Post-DFO group (IR+D (n = 10; (6 For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5; sham2: Pre+Post sterilized water group (n = 5; sham3: Post-sterilized water group (n = 5. The salivary flow rate (SFR was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR.Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells.

Adaptation and possible attenuation of Theileria parva-infected cells grown in irradiated mice

International Nuclear Information System (INIS)

Irvin, A.D.; Brown, C.G.D.; Stagg, D.A.; Kanhai, G.K.; Kimber, C.D.; Radley, D.E.

1976-01-01

Theileria parva-infected bovine lymphoid cells were taken from 8 cattle immediately after death from East Coast fever (ECF). Cells were inoculated into groups of irradiated Swiss and athymic nude mice. The irradiated mice were exposed to 800 rad doses from a 60 Co source. Cells became established in one group of Swiss mice and 2 groups of athymic mice. Development of cells in mice only occurred if cells concurrently established in culture; when establishment in culture was delayed, cells failed to develop in mice. Cells from one of the isolates in athymic mice were passaged 6 times through further mice. On inoculation of these mouse-passaged cells into cattle, the animals underwent mild reactions and subsequently resisted a lethal ECF challenge. The possibility of vaccinating cattle aginst ECF by means of mouse passaged cells merits further study. (author)

Behavioural consequences of an 8 Gy total body irradiation in mice: Regulation by interleukin-4

International Nuclear Information System (INIS)

Van der Meeren, A.; Lebaron-Jacobs, L.

2001-01-01

The effects of an 8 Gy γ total body irradiation (TBI) on exploration and locomotion activities as well as temperature were studied in C57BL6/J mice. Survival, body weight, and blood cell counts were also assessed in irradiated mice treated with placebo or interleukin (IL)-4. The efficacy of IL-4 treatment on improvement in exploration activity was evaluated. The study was carried out from 3 h to 30 days following exposure. Our results showed a biphasic response to irradiation concerning the exploration activity of mice. Irradiated mice had reduced activity as early as 3 h after exposure, with recovery of activity within 24 h. The exploration activity again decreased 4 days after irradiation and the recovery occurred slowly after day 17. IL-4 ameliorated the exploration status in mice in both phases. The locomotion activity was studied using a telemetry apparatus. A similar pattern to that of the exploration data was observed, with a minimal activity observed between days 13 and 17. A radiation-induced hypothermia was also noticed over the same time period. (author)

Behavioural consequences of an 8 Gy total body irradiation in mice: Regulation by interleukin-4

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Van der Meeren, A.; Lebaron-Jacobs, L. [Inst. de Protection et de Surete Nucleaire, Dept. de Protection de la sante de l' Homme et de Dosimetrie, Section Autonome de Radiobiologie Appliquee a la Medecine, IPSN, Fontenay-aux-Roses (France)

2001-02-01

The effects of an 8 Gy {gamma} total body irradiation (TBI) on exploration and locomotion activities as well as temperature were studied in C57BL6/J mice. Survival, body weight, and blood cell counts were also assessed in irradiated mice treated with placebo or interleukin (IL)-4. The efficacy of IL-4 treatment on improvement in exploration activity was evaluated. The study was carried out from 3 h to 30 days following exposure. Our results showed a biphasic response to irradiation concerning the exploration activity of mice. Irradiated mice had reduced activity as early as 3 h after exposure, with recovery of activity within 24 h. The exploration activity again decreased 4 days after irradiation and the recovery occurred slowly after day 17. IL-4 ameliorated the exploration status in mice in both phases. The locomotion activity was studied using a telemetry apparatus. A similar pattern to that of the exploration data was observed, with a minimal activity observed between days 13 and 17. A radiation-induced hypothermia was also noticed over the same time period. (author)

Meiotic chromosomal translocations in male mice induced by X-irradiation

Energy Technology Data Exchange (ETDEWEB)

Savkovic, N.; Pecevski; Vuksanovic, L.; Radivojevic, D.; Alavantic, D.

1983-01-01

The dose-response curve for reciprocal translocations induced by acute exposure of spermatogonial stem cells to X-rays in treated mice and their F-1 sons was examined. Male mice were totally irradiated with doses of 1Gy;5x1Gy and 5Gy. The obtained results show that frequency of the chromosomal translocations in directly treated animals is dose dependent. The percentage of animals irradiated with 1Gy which had the chromosomal translocations was 60, while this percentage in animals irradiated with single and fractionated dose of 5Gy was 100. The frequency of chromosomal translocations varies from 1.5% to 8.0%. Multivalent configurations in F-1 males were observed after exposure to 5Gy only. The incidence of F-1 translocated males was 17.5%.

Protective effect of gingerol on leucocyte and bone marrow DNA of 60Co γ-rays irradiated mice

International Nuclear Information System (INIS)

Xie Zhenfei; Zhou Yu; Geng Yanyan; Zeng Xianyin

2012-01-01

In this article, the effect of gingerol on peripheral leucocyte and bone marrow DNA of 60 Co γ-rays irradiated mice was developed., Twenty-four healthy healthy female Kunming mice were randomly divided into 4 groups: control, gingerol, irradiation and gingerol + irradiation group. Gingerol group and gingerol + irradiation group were given gingerol intragastrically once a day for five days. Irradiation group and gingerol + irradiation group were suffered from 5 Gy 60 Co γ-rays irradiation at the rate of 1.2 Gy/min on the 6 th day. Blood samples, spleens, livers and thigh bones were collected to be measured after 48 h. The results showed that, compared with irradiation group, gingerol + irradiation group had significantly higher spleen index (p 60 Co γ-rays irradiated mice. (authors)

Some effects of irradiation of mice in utero with tritiated compounds

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Lambert, B E; Phipps, M L [Radiobiology Department, The Medical College of Bartholomew' s Hospital, London, UK

1978-01-01

Mice have been exposed continuously, in utero, to tritiated water (via the maternal drinking water) or to tritiated thymidine (infused continuously into the mother). In both cases the patterns of labeling and subsequent loss of tritium over an extended period have been studied. The technique of infusion in unrestrained mice and its application in the production of fully tritium-labeled offspring is described in some detail. These fully labeled mice are being used to study a number of early and late effects, in particular, gonad cell effects and carcinogenesis, following this form of internal irradiation. Some preliminary results are presented. Similar results produced by homogeneous irradiation from tritiated water are also reported.

Some effects of irradiation of mice in utero with tritiated compounds

International Nuclear Information System (INIS)

Lambert, B.E.; Phipps, M.L.

1978-01-01

Mice have been exposed continuously, in utero, to tritiated water (via the maternal drinking water) or to tritiated thymidine (infused continuously into the mother). In both cases the patterns of labeling and subsequent loss of tritium over an extended period have been studied. The technique of infusion in unrestrained mice and its application in the production of fully tritium-labeled offspring is described in some detail. These fully labeled mice are being used to study a number of early and late effects, in particular, gonad cell effects and carcinogenesis, following this form of internal irradiation. Some preliminary results are presented. Similar results produced by homogeneous irradiation from tritiated water are also reported. (Auth.)

Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

International Nuclear Information System (INIS)

Zou, Yani; Leu, David; Chui, Jennifer; Fike, John R.; Huang, Ting-Ting

2013-01-01

Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted

Development of infection with Streptococcus bovis and Aspergillus sp. in irradiated mice after glycopeptide therapy

International Nuclear Information System (INIS)

Brook, I.; Tom, S.P.; Ledney, G.D.

1993-01-01

The use of ofloxacin and glycopeptides was evaluated for the treatment of infections arising in C3H/HeN female mice irradiated with 8.3 Gy from a 60 Co source. The 21 day regimen began 72 h after irradiation when each of five sets of experimental animals received three antimicrobial therapy regimens and a saline-treated control group. With 40 mice in each group, 20 were used to monitor survival, 20 for the recovery of bacteria from the liver culture. Treatment groups were oral ofloxacin; oral or intramuscular vancomycin oral teicoplanin, ofloxacin and vancomycin; ofloxacin and teicoplanin; or saline. Bacteria recovered from saline treated mice were Enterobacteriaceae and Streptococcus spp. By comparison, fewer Enterobacteriaceae were isolated from ofloxacin treated mice and fewer Streptococcus spp. in both vancomycin and teicoplanin treated mice. However, glycopeptide-treated mice developed infection with Aspergillis fumigatus and glycopeptide resistant Streptococcus bovis. Mortality rates within 60 days of irradiation were 100% in all treatment and control groups with the exception of ofloxacin which was 25%-35%. These data suggest that glycopeptide therapy increases rates of systemic infection with fungi and antibiotic resistant bacteria in irradiated mice. (Author)

Development of infection with Streptococcus bovis and Aspergillus sp. in irradiated mice after glycopeptide therapy

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Brook, I.; Tom, S.P.; Ledney, G.D. (Armed Forces Radiobiology Research Inst., Bethesda, MD (United States))

1993-11-01

The use of ofloxacin and glycopeptides was evaluated for the treatment of infections arising in C3H/HeN female mice irradiated with 8.3 Gy from a [sup 60]Co source. The 21 day regimen began 72 h after irradiation when each of five sets of experimental animals received three antimicrobial therapy regimens and a saline-treated control group. With 40 mice in each group, 20 were used to monitor survival, 20 for the recovery of bacteria from the liver culture. Treatment groups were oral ofloxacin; oral or intramuscular vancomycin oral teicoplanin, ofloxacin and vancomycin; ofloxacin and teicoplanin; or saline. Bacteria recovered from saline treated mice were Enterobacteriaceae and Streptococcus spp. By comparison, fewer Enterobacteriaceae were isolated from ofloxacin treated mice and fewer Streptococcus spp. in both vancomycin and teicoplanin treated mice. However, glycopeptide-treated mice developed infection with Aspergillis fumigatus and glycopeptide resistant Streptococcus bovis. Mortality rates within 60 days of irradiation were 100% in all treatment and control groups with the exception of ofloxacin which was 25%-35%. These data suggest that glycopeptide therapy increases rates of systemic infection with fungi and antibiotic resistant bacteria in irradiated mice. (Author).

Lifespan studies on different strains of mice exposed chronically to low levels of whole body gamma irradiation

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Fox, L.A.; Klein, A.K.; Cain, G.R.; Rosenblatt, L.S.

1982-01-01

Several strains of mice, chosen for their predisposition to immunohematological disorders, were exposed to low levels of 60 irradiation continuously for four weeks. All individuals were subsequently followed throughout their lifetimes. W/W/sup v/ mice, which are tyically subject to a stem cell deficiency, had a lower cumulative survival rate for the irradiated group than for the unirradiated controls. Irradiated RF/sub j/ mice had a dramatically lower cumulative survival rate than their unirradiated controls. Conversely, BXSB mice, which have a lumphoproliferative autoimmune disorder, had a higher cumulative survival rate after chronic irradiation than did unirradiated BXSBs. Irradiation had no effect upon the survival rate curves of the NZB strain, the murine model for Lupus Erythematosus

Protective effect of alkali extract of Huangmo (AEHM) on immunological function in X-irradiated mice

International Nuclear Information System (INIS)

Ye Fei; Wu Congmei; Su Shijie; Cao Ruimin

1996-01-01

The male mice were given ip AEHM 5 mg/kg, wt/d before irradiation with 2.0 Gy X-rays for 3 days, and the changes of several immunological indexes were observed 24 h after X-irradiation. The results showed that AEHM significantly increased the numbers of splenocytes and thymocytes, the reaction of splenocytes to ConA and the spontaneous proliferation of thymocytes in irradiated mice, and decreased the fall of spleen and thymus. In addition, a tendency of the increases in the above indexes in the intact mice treated with AEHM was observed. Meanwhile, AEHM possessed similar radioprotective effect on immunological functions to polysaccharides of Ginseng. The results suggest that AEHM has not only a radioprotective effect on immunological functions in the irradiated mice, but also an enhancing effect on the defence functions in the intact mice. It is very hopeful that AEHM acted as immune-enhanced drug should be used in the clinic

The effects of in utero irradiation on mutation induction and transgenerational instability in mice

International Nuclear Information System (INIS)

Barber, Ruth C.; Hardwick, Robert J.; Shanks, Morag E.; Glen, Colin D.; Mughal, Safeer K.; Voutounou, Mariel; Dubrova, Yuri E.

2009-01-01

Epidemiological evidence suggests that the deleterious effects of prenatal irradiation can manifest during childhood, resulting in an increased risk of leukaemia and solid cancers after birth. However, the mechanisms underlying the long-term effects of foetal irradiation remain poorly understood. This study was designed to analyse the impact of in utero irradiation on mutation rates at expanded simple tandem repeat (ESTR) DNA loci in directly exposed mice and their first-generation (F 1 ) offspring. ESTR mutation frequencies in the germline and somatic tissues of male and female mice irradiated at 12 days of gestation remained highly elevated during adulthood, which was mainly attributed to a significant increase in the frequency of singleton mutations. The prevalence of singleton mutations in directly exposed mice suggests that foetal irradiation results in genomic instability manifested both in utero and during adulthood. The frequency of ESTR mutation in the F 1 offspring of prenatally irradiated male mice was equally elevated across all tissues, which suggests that foetal exposure results in transgenerational genomic instability. In contrast, maternal in utero exposure did not affect the F 1 stability. Our data imply that the passive erasure of epigenetic marks in the maternal genome can diminish the transgenerational effects of foetal irradiation and therefore provide important clues to the still unknown mechanisms of radiation-induced genomic instability. The results of this study offer a plausible explanation for the effects of in utero irradiation on the risk of leukaemia and solid cancers after birth.

Time-effect relationship of immunological adaptive response induced by low dose X-irradiation in mice

International Nuclear Information System (INIS)

Zhao Yong; Gong Shouliang; Liu Shuzheng

1995-01-01

Kunming mice irradiated with whole-body X-rays were used to observe time-effect relationship of immunological adaptive response induced by ionizing radiation. The results showed that pre-irradiation dose of 75 mGy X-rays with the intervals of 6-48 h between pre-irradiation and challenge irradiation could induce immunological adaptive response in the spontaneous proliferation of thymocytes and the responses of splenocytes to Con A and LPS in mice at 18-24 h after challenge irradiation with 1.5-2.0 Gy X-rays

Antibiotic radioprotection of mice exposed to supralethal whole-body irradiation independent of antibacterial activity

International Nuclear Information System (INIS)

Mastromarino, A.; Wilson, R.

1976-01-01

Oral administration of streptomycin, kanamycin, neomycin, or gentamicin to specific pathogen-free C57 x Af mice in their drinking water (4 mg/ml) for 2 weeks before supralethal whole-body irradiation very significantly prolonged their mean survival times (8.2 to 8.9 days vs 6.9 for controls) to values which exceed those reported for germ-free mice (7.3 days). The total fecal concentrations of aerobes and anaerobes were reduced by kanamycin, neomycin, and gentamicin. Streptomycin reduced the anaerobes significantly, but not the aerobes. Unlike germ-free mice, these antibiotic-treated mice did excrete free bile acids, products of bacterial action. Oral antibiotic treatment was ineffective in altering the transit time of the intestinal mucosal cells. Previously reported studies had indicated a correlation between decreased transit time and increased survival after irradiation. No significant correlation between mean survival time after irradiation and mucosal transit time was observed. The data demonstrate that certain antibiotics alter the character of the intestinal bacterial flora and increase protection against supralethal doses of whole-body irradiation. It is concluded that the mechanisms of radioresistance in antibiotic-treated mice and germ-free mice are different and that in both groups radioresistance is the result of more than elimination of postirradiation infection

Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice.

Science.gov (United States)

Satoh, T; Murata, M; Iwabuchi, N; Odamaki, T; Wakabayashi, H; Yamauchi, K; Abe, F; Xiao, J Z

2015-01-01

Probiotics have been shown to have a preventative effect on skin photoaging induced by short term UV irradiation, however, the underlying mechanisms and the effect of probiotics on skin photoaging induced by chronic UV irradiation remain unclear. In this study, we investigated the effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in hairless mice. Mice were irradiated with UVB three times weekly and orally administered B. breve B-3 (2×10(9) cfu/mouse /day) for 7 weeks. Nonirradiated mice and UVB-irradiated mice without probiotic treatment were used as controls. B. breve B-3 significantly suppressed the changes of transepidermal water loss, skin hydration, epidermal thickening and attenuated the damage to the tight junction structure and basement membrane induced by chronic UVB irradiation. Administration of B. breve B-3 tended to suppress the UV-induced interleukin-1β production in skin (P=0.09). These results suggest that B. breve B-3 could potentially be used to prevent photoaging induced by chronic UV irradiation.

Effect of antimicrobial therapy on bowel flora and bacterial infection in irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Brook, Itzhak; Walker, R.I.; MacVittie, T.J.

1988-05-01

Mice exposed to 10 Gy cobalt-60 radiation were given intramuscular antimicrobial therapy of gentamicin, metronidazole, or a combination. Mortality in mice treated with metronidazole alone or in combination with gentamicin occurred earlier than in controls (P < 0.001). Microorganisms were recovered from blood, spleen, and liver of the metronidazole-treated mice earlier than from other groups. Predominant organisms recovered from these animals were Enterobacteriaceae. Quantitative cultures of ileal flora showed decrease in aerobic, facultative anaerobic and strict anaerobic bacteria after irradiation, and a subsequent increase only in the number of strict aerobic bacteria. Compared to untreated mice, a rapid decrease (by 8.8 logs) in anaerobic flora occurred in mice treated with metronidazole 5 days after irradiation, followed by a rapid increase in the number of aerobic organisms which coincided with the earlier mortality in this group. Data suggest that antimicrobial agents decreasing the number of the strict anaerobic component of the gut flora enhance systemic infection by aerobic or facultative anaerobic bacteria, facilitating post-irradiation mortality.

Effect of antimicrobial therapy on bowel flora and bacterial infection in irradiated mice

International Nuclear Information System (INIS)

Brook, Itzhak; Walker, R.I.; MacVittie, T.J.

1988-01-01

Mice exposed to 10 Gy cobalt-60 radiation were given intramuscular antimicrobial therapy of gentamicin, metronidazole, or a combination. Mortality in mice treated with metronidazole alone or in combination with gentamicin occurred earlier than in controls (P < 0.001). Microorganisms were recovered from blood, spleen, and liver of the metronidazole-treated mice earlier than from other groups. Predominant organisms recovered from these animals were Enterobacteriaceae. Quantitative cultures of ileal flora showed decrease in aerobic, facultative anaerobic and strict anaerobic bacteria after irradiation, and a subsequent increase only in the number of strict aerobic bacteria. Compared to untreated mice, a rapid decrease (by 8.8 logs) in anaerobic flora occurred in mice treated with metronidazole 5 days after irradiation, followed by a rapid increase in the number of aerobic organisms which coincided with the earlier mortality in this group. Data suggest that antimicrobial agents decreasing the number of the strict anaerobic component of the gut flora enhance systemic infection by aerobic or facultative anaerobic bacteria, facilitating post-irradiation mortality. (author)

Protective Effect of HemoHIM on Epidermal Melanocytes in Ultraviolet-B irradiated Mice

Energy Technology Data Exchange (ETDEWEB)

Lee, Hae June [Korea Institute of Radiological and Medical Science, Seoul (Korea, Republic of); Kim, Jong Choon; Moon, Chang Jong; Kim, Sung Ho [Chonnam National University, Gwangju (Korea, Republic of); Jung, U Hee; Park, Hae Ran; Jo, Sung Kee [Jeongeup Campus of Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Jang, Jong Sik; Kim, Tae Hwan [Kyungpook National University, Daegu (Korea, Republic of)

2011-06-15

We induced the activation of melanocytes in the epidermis of C57BL/6 mice by ultraviolet-B (UV-B) irradiation, and observed the effect of an herbal preparation (HemoHIM, HH) on the formation, and decrease of UV-B-induced epidermal melanocytes. C57BL/6 mice were irradiated by UV-B 80 mJ:cm{sup -2} (0.5 mW:sec{sup -1}) daily for 7 days, and HH was intraperitoneally, orally or topically applied pre- or post-irradiation. For the estimation of change of epidermal melanocytes, light microscopic observation with dihydroxyphenylalanine (DOPA) stain was performed. Split epidermal sheets prepared from the ear of untreated mice exhibited 13∼15 melanocytes:mm{sup -2}, and one week after UV irradiation, the applied areas showed an increased number of strongly DOPA-positive melanocytes with stout dendrites. But intraperitoneal, oral or topical treatment with HH before each irradiation interrupted UV-B-induced pigmentation and resulted in a marked reduction in the number of epidermal melanocytes as compared to the number found in UV-B-irradiated, untreated control skin. The number and size of DOPA-positive epidermal melanocytes were also significantly decreased in intraperitoneally injected or topically applicated group after irradiation with HH at 3rd and 6th weeks after irradiation. The present study suggests the HH as inhibitor of UV-B-induced pigmentation, and depigmenting agent.

Differentiation of strains of yellow fever virus in γ-irradiated mice

International Nuclear Information System (INIS)

Fitzgeorge, R.; Bradish, C.J.

1980-01-01

The mouse sensitized by optimal, sub-lethal γ-irradiation has been used for the differentiation of strains of yellow fever virus and for the resolution of their immunogenicity and pathogenicity as distinct characteristics. For different strains of yellow fever virus, the patterns of antibody-synthesis, regulatory immunity (pre-challenge) and protective immunity (post-challenge) are differentially sensitive to γ-irradiation. These critical differentiations of strains of yellow fever virus in γ-irradiated mice have been compared with those shown in normal athymic and immature mice in order to elucidate the range of quantifiable in vivo characteristics and the course of the virus-host interaction. This is discussed as a basis for the comparisons of the responses of model and principal hosts to vaccines and pathogens. (author)

Slow elimination of injured liver DNA bases of γ-irradiated old mice

International Nuclear Information System (INIS)

Gaziev, A.I.; Malakhov, L.V.; Fomenko, L.A.

1982-01-01

The paper presents a study of the elimination of injured bases from the liver DNA of old and young mice after their exposure to γ rays. The presented data show that if DNA from the liver of irradiated mice is treated with incision enzymes, its priming activity is increased. In the case of enzymatic treatment of DNA isolated 5 h after irradiation we find a great difference between the priming activity of the liver DNA of old and young mice. The reason for this difference is that the liver DNA of 20-month old mice 5 h after irradiation still has many unrepaired injured bases. These data indicated that the rate of incision of γ-injured DNA bases in the liver of old mice is lower than in the liver of young mice. In the liver of mice of different age the rate of restitution of DNA, single-strand breaks induced by γ rays in doses up to 100 Gy is the same. At the same time, the level of induced reparative synthesis of DNA in cells of an old organism is lower than in cells of a young organism. The obtained data suggest that reduction of the rate of elimination of modified bases from the cell DNA of 20-month old mice is due to reduction of the activity of the DNA repair enzymes or to restrictions in the chromatin in the access of these enzymes to the injured regions of DNA in the cells of old animals

Protective effect of intermittent fasting on the mortality of gamma-irradiated mice

International Nuclear Information System (INIS)

Kozubik, A.; Pospisil, M.

1982-01-01

The effect of 1 to 6 weeks' adaptation to intermittent fasting (alternating periods of 24 h fasting and subsequent 24 h feeding) on the manifestations of radioresistance of mice subjected to whole-body gamma-irradiation was studied. A favourable effect of this feeding regimen on the survival of irradiated animals was observed. The optimal redioprotective effect was achieved in mice adapted to intermittent fasting for 2 to 3 weeks and irradiated after 24 h of food intake. Furthermore, it was shown that the radioresistance of the adapted organism depends on the momentary state of food intake. After renewal of the normal ad libitum feeding the adaptively induced radioresistance decreases. (orig.) [de

Protective effect of intermittent fasting on the mortality of gamma-irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Kozubik, A.; Pospisil, M.

1982-12-01

The effect of 1 to 6 weeks' adaptation to intermittent fasting (alternating periods of 24 h fasting and subsequent 24 h feeding) on the manifestations of radioresistance of mice subjected to whole-body gamma-irradiation was studied. A favourable effect of this feeding regimen on the survival of irradiated animals was observed. The optimal redioprotective effect was achieved in mice adapted to intermittent fasting for 2 to 3 weeks and irradiated after 24 h of food intake. Furthermore, it was shown that the radioresistance of the adapted organism depends on the momentary state of food intake. After renewal of the normal ad libitum feeding the adaptively induced radioresistance decreases.

Protective effect of intermittent fasting on the mortality of gamma-irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Kozubik, A; Pospisil, M

1982-12-01

The effect of 1 to 6 weeks' adaptation to intermittent fasting (alternating periods of 24 h fasting and subsequent 24 h feeding) on the manifestations of radioresistance of mice subjected to whole-body gamma-irradiation was studied. A favourable effect of this feeding regimen on the survival of irradiated animals was observed. The optimal redioprotective effect was achieved in mice adapted to intermittent fasting for 2 to 3 weeks and irradiated after 24 h of food intake. Furthermore, it was shown that the radioresistance of the adapted organism depends on the momentary state of food intake. After renewal of the normal ad libitum feeding the adaptively induced radioresistance decreases.

Effect of rTMP-GH recombinant fusion protein on thrombocytopoiesis in irradiation injured mice

International Nuclear Information System (INIS)

Xu Yang; Wang Junping; Chen Fang; Shen Mingqiang; Chen Mo; Wang Song; Ran Xinze; Su Yongping; Kai Li

2009-01-01

Objective: To investigate the in vivo effects of rTMP-GH recombinant fusion protein on thrombocytopoiesis in mice with thrombopenia inflicted by irradiation. Methods: BALB/C mice weighting around 20 g were irradiated with 5 Gy of 60 Co γ-ray irradiation to generate thrombopenia. The irradiation injured mice were injected with rTMP-GH or rhGH subcutaneously at the dose of 200 (μg ·kg -1 · d -1 for 7 days. From the 6 th day, the platelets in blood samples from vena caudalis were counted routinely, and the pathological changes of bone marrow were determined by morphological observation. Results: From the 10 th day, the levels of blood platelet in rTMP-GH treated mice were much higher than those of rhGH treatment group and normal saline (NS) control group, especially at the nadir (P < 0.01). On the 22 nd day, the platelet count has recovered up to 80% of normal level in rTMP-GH treatment group, while it has just recovered up to 30% in NS control group. Morphological observation showed that there was obvious reconstruction of bone marrow in mice treated with rTMP-GH, compared with NS group.The number of megarkaryoblasts and megakaryocytes in bone marrow of rTMP-GH treated mice (3.07 ± 0.32) was much higher than those of rhGH treatment group (2.20 ± 0.22, P < 0.05) and NS control group (0.87 ± 0.19, P <0.01). Conclusions: rTMP-GH has potent effects on the recovery of blood platelet by promoting megarkaryocytopoiesis in irradiation injuried mice. (authors)

Scheduled transplantation of human umbilical cord blood to severe combined immunodeficient mice

International Nuclear Information System (INIS)

Wu Jianqiu; Yang Yunfang; Jin Zhijun; Cai Jianming; Yang Rujun; Xiang Yingsong

2000-01-01

Objective: To explore a new method for developing the efficiency of human umbilical cord blood (UCB) cells engraftment, and further understand the growth characteristic of hematopoietic stem cells (HSC) in vivo. Methods: Sublethally irradiated severe combined immunodeficient (SCID) mice were transplanted i.v. with UCB cells which had been cryo-preserved at -80 degree C. The human cells in recipient mice were detected by flow cytometry and CFU-GM assay. Results: In contrast to the single transplantation, scheduled engraftment of similar numbers of UCB cells resulted in a proportionally obvious increase in the percentages of CD45 + , CD34 + cells produced in SCID mouse bone marrow (BM). When the donor cells were reduced to 20 percent, an identical reconstitution of both hematopoietic and part of immunologic functions was achieved. Conclusion: Scheduled engraftment improves the repopulating ability of HSC, which would provide a novel way for clinical cord blood engraftment in adult objects

Survival of irradiated mice treated with WR-151327, synthetic trehalose dicorynomycolate, or ofloxacin

Science.gov (United States)

Ledney, G. D.; Elliott, T. B.; Landauer, M. R.; Vigneulle, R. M.; Henderson, P. L.; Harding, R. A.; Tom, S. P.

1994-10-01

Spaceflight personnel need treatment options that would enhance survival from radiation and would not disrupt task performance. Doses of prophylactic or therapeutic agents known to induce significant short-term (30-day) survival with minimal behavioral (locomotor) changes were used for 180-day survival studies. In protection studies, groups of mice were treated with the phosphorothioate WR-151327 (200 mg/kg, 25% of the LD10) or the immunomodulator, synthetic trehalose dicorynomycolate (S-TDCM; 8 mg/kg), before lethal irradiation with reactor-generated fission neutrons and γ-rays (n/γ = 1) or 60Co γ-rays. In therapy studies, groups of mice received either S-TDCM, the antimicrobial ofloxacin, or S-TDCM plus ofloxacin after irradiation. For WR-151327 treated-mice, survival at 180 days for n/γ = 1 and γ-irradiated mice was 90% and 92%, respectively; for S-TDCM (protection), 57% and 78%, respectively; for S-TDCM (therapy), 20% and 25%, respectively; for ofloxacin, 38% and 5%, respectively; for S-TDCM combined with ofloxacin, 30% and 30%, respectively; and for saline, 8% and 5%, respectively. Ofloxacin or combined ofloxacin and S-TDCM increased survival from the gram-negative bacterial sepsis that predominated in n/γ = 1) irradiated mice. The efficacies of the treatments depended on radiation quality, treatment agent and its mode of use, and microflora of the host.

Effects of Ganoderma lucidum on cellular immunocompetence in gamma-irradiated mice

Energy Technology Data Exchange (ETDEWEB)

WangChi, Chen; DouMong, Hau [Institute of Radiation Biology, National Tsing Hua University, Hsinchu (China)

1995-07-01

We have investigated the effects on mice treated with Ganoderma lucidum (Gl) when the whole body was exposed to 400 rad gamma-irradiation. The mice were divided into five groups. Group A was the normal control; group B, the experimental control, was treated with GI; group C was the radiation control (RT); group D was treated with RT and Gl; group E was treated with Gl, RT and Gl. The results revealed that the relative spleen weight had increased significantly in groups B and E on day 7 and increased in all experimental groups on day, 28 after irradiation. The leukocyte counts decreased obviously in groups C, D and E on day 7, and recovered in groups D and E was faster than that in group C on day 28. The blastogenic response of splenocytes to LPS, Con A and PHA in groups administered GI were higher than that in group C on days 7and 28. Therefore, Gl seemed to assist the recovery of cellular immunocompetence in gamma-irradiated mice. (author)

Effects of Ganoderma lucidum on cellular immunocompetence in gamma-irradiated mice

International Nuclear Information System (INIS)

Chen WangChi; Hau DouMong

1995-01-01

We have investigated the effects on mice treated with Ganoderma lucidum (Gl) when the whole body was exposed to 400 rad gamma-irradiation. The mice were divided into five groups. Group A was the normal control; group B, the experimental control, was treated with GI; group C was the radiation control (RT); group D was treated with RT and Gl; group E was treated with Gl, RT and Gl. The results revealed that the relative spleen weight had increased significantly in groups B and E on day 7 and increased in all experimental groups on day, 28 after irradiation. The leukocyte counts decreased obviously in groups C, D and E on day 7, and recovered in groups D and E was faster than that in group C on day 28. The blastogenic response of splenocytes to LPS, Con A and PHA in groups administered GI were higher than that in group C on days 7and 28. Therefore, Gl seemed to assist the recovery of cellular immunocompetence in gamma-irradiated mice. (author)

Concentration of metallothionein in mice livers after a small dose of irradiation

Energy Technology Data Exchange (ETDEWEB)

Saitou, Mikio; Yanai, Takanori; Hasegawa, Hidenao; Otsu, Hiroshi; Sato, Fumiaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan); Akata, Naofumi; Kanaiwa-Kudo, Shouko; Matsumoto, Tsuneya; Noda, Yuko

1998-12-01

This study was made to determine whether metallothionein (MT) is induced by a small dose (0.5 Gy) irradiation. One hundred B6C3F1/Nrs mice of each sex, 8-10 weeks old, were used in the sham study (unirradiated controls) and experimental (irradiated) groups. Eighty mice of each sex were given acute whole body irradiation with {sup 197}Cs{gamma}-rays under SPF conditions; two doses of 0.5 and 5.0 Gy at 30 cm distance from the source at the rate of 0.563 Gy/min. Twenty mice of each sex were used in the sham study. Every ten male and female mouse was killed by cervical dislocation on days 1, 7, 14 and 21 after irradiation. The same numbers of male and female control mice were killed on days 0 and 21. Livers were removed immediately after death, and concentration of MT was examined. In both the males and females, the MT concentration of the 5 Gy-group peaked on the first day after irradiation, and there was no difference in comparison with the control values between the 7th and 21st days. In contrast, on no day did the MT concentration for the 0.5 Gy-group showed a significant difference from the control group. The time dependency patterns of the female and male mice also showed no significant differences for 5 Gy- and 0.5 Gy-groups, but the mean values of the MT concentration was lower in the males than in the females on the 1st day. Results of the direct quantitation of MT by the enzyme-linked immunoabsorbent assay (ELISA) also showed peak MT accumulation on the 1st day for both male and female mice. These were also shown by the atomic absorption spectrometry (AAS) and the inductively coupled plasma mass spectrometry (ICP-MS) analyses. But peak heights for the males and females showed a tendency inverse to that of the AAS and ICP-MS analyses. This discrepancy is attributable to the technical problem encountered in the experiment. On the basis of our findings, MT does not seem to be related to acquired radioresistance in mice. (K.H.)

Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10.D2----B10)

International Nuclear Information System (INIS)

Ildstad, S.T.; Wren, S.M.; Bluestone, J.A.; Barbieri, S.A.; Stephany, D.; Sachs, D.H.

1986-01-01

Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. Experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it

Effects of low dose rate irradiation on life span prolongation of human premature-aging syndrome model mice

International Nuclear Information System (INIS)

Nomura, Takaharu

2006-01-01

We previously showed that Type II diabetes model mice prolonged of their life span by life long low dose rate irradiation. We also found that antioxidant function in variety tissues of some strain of mice were enhancement after low dose/low dose rate irradiation. The prolongation of life span might depend on certain damaged level of reactive oxygen species. We thought the effect of the prolongation was due to the enhancement of the antioxidant activities after irradiation. We investigated whether the enhancement of antioxidant activities after low dose rate irradiation had an effect on life span prolongation. Four-week-old female human premature-aging syndrome model mice, kl/kl (klotho) mice, which the life span of this model mouse is about 65 days, were irradiated with gamma rays at 0.35, 0.70 or 1.2 mGy/hr. The 0.70 mGy/hr-irradiated group remarkably effected on the prolongation of their life span. Some mice of the group were extremely survived for about and more 100 days. Antioxidant activities in the irradiated groups were enhancement by low dose rate irradiation, however the dependence of the dose rates were not clearly difference. These results suggest that the antioxidant activities in this model mouse were enhanced by the low dose rate irradiation, and may make it possible to prolong the life span of this mouse. (author)

Reactivation of Immunological Response in Lethally X-Irradiated Mice Treated with Isogeneic Bone Marrow

Energy Technology Data Exchange (ETDEWEB)

Stankovic, V.; Slijepcevic, M.; Hrsak, I. [Institute Ruder Boskovic, Zagreb, Yugoslavia (Croatia)

1968-08-15

Male and female C57BL/H and CBA/H mice aged 10-12 weeks were used as recipients and donors, respectively. All recipient mice were given a lethal whole-body X-irradiation dose (850 R for C57BL and 950 R for CBA mice) followed by iv injection of 10 x 106 isogeneic eosin-negative bone-marrow cells suspended in 0.5 ml of Hank's solution. The number of eosin-positive cells was less than 10%. The state of immunological responsiveness of irradiated recipients was measured at different time intervals up to 86 days after irradiation. The immune response to bacterial antigen was measured with the titre of agglutinating antibodies in serum six days after iv antigenic stimulation with a suspension of 2 x 10{sup 7} killed Salmonella typhimurium cells. The immune response to tissue antigens was evaluated by: (a) the effectiveness of the spleen cells from isologous radiation chimeric parental mice in preventing bone marrow from F{sub 1} (C57BL x CBA) hybrid donor from therapeutically affecting lethally irradiated F j recipient mice; (b) the effectiveness of the spleen cells in inducing splenom egaly in recipient F{sub 1} hybrid mice (Simonsen test). It was found that the responsiveness to bacterial antigens reappears much earlier and increases much faster than the immunological responsiveness to tissue antigens. (author)

The effects of three types of macrophages culture supernatant on CFU-GM in irradiated mice

International Nuclear Information System (INIS)

Quan Hongxun; Fu Li; Zhao Fengchen; Han Fen

2008-01-01

Objective: To study the effects of peritional macrophyge(PM), alveolar macrophage (AM), and Kupffer cell (KC) on colony forming unite granulacyte/macrophage (CFU -GM) in irradiated mice. Methods: Using techniques of hemopoietic progenitors in vitro, the authors studied the effects of three types of macrophages culture supernatant on CFU - GM. Results: It is shown that three types of macrophages culture supernatant may stimulate proliferation and differentiation of CFU-GM in irradiated mice, and KC is the best one in comparison to others. Conclusion: three types of macrophages culture supernatant may protect CFU-GM irradiated mice with KC being the best method. (authors)

Accumulation of lipid peroxidation products in eye structures of mice subjected to whole-body X-irradiation

International Nuclear Information System (INIS)

Sakina, N.L.; Dontsov, A.E.; Afanas'ev, G.G.; Ostrovskij, M.A.; Pelevina, I.I.

1990-01-01

In studying the effect of whole-body X-irradiation on the accumulation of lipid peroxidation products (conjugated dienes, TBA-active products, and Sciff bases) in retina and retinal pigmented epithelium of pigmented and nonpigmented mice it was shown that irradiation of dark-pigmented mice does not cause even a slight accumulation of lipid peroxidation products as compared to that in the controls. Albino mice exhibited a marked increase in the level of lipid peroxidation products which was manifested soon after irradiation and persisted for at least 3 months after irradiation. Melanine is suggested to participate in protecting eye structures against pro-oxidizing action of ionizing radiation

The effect of natural hot environment on survival and peripheral blood lymphocytes in γ-irradiated mice

International Nuclear Information System (INIS)

Zhou Meijuan; Zheng Li; Ding Zhenhua

2004-01-01

Objective: To study the effect of natural hot environment (NHE) on survival and peripheral blood lymphocytes in γ-irradiated in mice. Methods: After γ-irradiation at the dosage of 6.5 or 9.0 Gy, the mice were exposed to NHE for 0, 3, 6, 9 h or 30 days. After exposure to NHE, mice of the 6 h and 9 h groups, were then bred at room temperature. The survival and peripheral blood lymphocytes were observed for 30 days. Results: There were obvious differences in survival time between the groups that were exposed to NHE for 9 h and 30 d and that of the 0 h group, the mice of these three groups having been irradiated with 6.5 Gy. For 9.0 Gy-irradiated mice, the survival times of the 6, 9 h and 30 d groups were all significantly shorter than that of the 0 h group. The descending rate of peripheral blood lymphocytes in 0 h group is smaller than that of all NHE groups. There was no lymphocyte fluctuate resuscitation in all NHE groups as seen in the 0 h group. Conclusion: There is a significant decrease of survival indexes and a faster descending rate of peripheral blood lymphocytes in mice exposed to after γ-irradiation. (authors)

Stem cell factor enhances the survival of murine intestinal stem cells after photon irradiation

International Nuclear Information System (INIS)

Leigh, B.R.; Khan, W.; Hancock, S.L.

1995-01-01

Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic cell is clinically relevant. Gastrointestinal toxicity is common during and after abdominal and pelvic radiation therapy and limits the radiation dose in these regions. As observed with bone marrow, the administration of SCF to mice prior to TBI enhanced the survival of mouse duodenal crypt stem cells. The maximum enhancement of survival was seen when 100 μ/kg of SCF was given intraperitoneally 8 h before irradiation. This regimen increased the survival of duodenal crypt stem cells after 12.0 Gy TBI from 22.5 ± 0.7 per duodenal cross section for controls to 30.0 ± 1.7 after treatment with SCF (P=0.03). The TBI dose producing 50% mortality of 6 days (LD 50/6 ) was increased from 14.9 Gy for control mice to 19.0 Gy for mice treated with SCF (dose modification factor = 1.28). These findings demonstrate that SCF (dose modification factor = 1.28). These findings demonstrate that SCF has radioprotective effects on a non-hematopoietic stem cell population and suggest that SCF may be of clinical value in preventing radiation injury to the intestine. 29 refs., 4 figs

Immunological network activation by low-dose rate irradiation. Analysis of cell populations and cell surface molecules in whole body irradiated mice

International Nuclear Information System (INIS)

Ina, Yasuhiro; Sakai, Kazuo

2003-01-01

The effects of low-dose rate whole body irradiation on biodefense and immunological systems were investigated using female C57BL/6 (B6) mice. These B6 mice were exposed continuously to γ-rays from a 137 Cs source in the long-term low-dose rate irradiation facility at CRIEPI for 0 - 12 weeks at a dose rate of 0.95 mGy/hr. In the bone marrow, thymus, spleen, lymph nodes, and peripheral blood of the irradiated mice, changes in cell populations and cell surface molecules were examined. The cell surface functional molecules (CD3, CD4, CD8, CD19, CD45R/B220, ICAM-1, Fas, NK-1.1, CXCR4, and CCR5), and activation molecules (THAM, CD28, CD40, CD44H, CD70, B7-1, B7-2, OX-40 antigen, CTLA-4, CD30 ligand, and CD40 ligand) were analyzed by flow cytometry. The percentage of CD4 + T cells and cell surface CD8 molecule expressions on the CD8 + T cells increased significantly to 120-130% after 3 weeks of the irradiation, compared to non-irradiated control mice. On the other hand, the percentage of CD45R/B220 + CD40 + B cells, which is one of the immunological markers of inflammation, infection, tumor, and autoimmune disease, decreased significantly to 80-90% between the 3rd to 5th week of irradiation. There was no significant difference in other cell population rates and cell surface molecule expression. Furthermore, abnormal T cells bearing mutated T cell receptors induced by high-dose rate irradiation were not observed throughout this study. These results suggest that low-dose rate irradiation activates the immunological status of the whole body. (author)

Radio -Protective Role of Zinc Administration Pre-Exposure to Gamma-Irradiation in Male Albino Mice

International Nuclear Information System (INIS)

El-Dawy, H.A.; Aly El-Sayed, S.M.

2004-01-01

This study was performed to evaluate the potency of zinc chloride injected subcutaneously (30 mg/kg b.w.) in male albino mice as a radio-protective agent pre exposure to gamma-irradiation. The investigation of the radio-protective role of zinc chloride was accomplished through measuring the levels of sex hormones, and observation of the chromosomal aberrations and sperm-head abnormalities after exposure to gamma-irradiation. The average of abnormal cells with chromosomal aberration and abnormal sperm % on the 7 th and 21 th days were 32% and 40%, and 14% and 22% respectively in mice exposed to radiation alone compared to 12% and 16%, and 5% and 12% respectively in mice treated with zinc chloride pre-irradiation. Treatment of mice with zinc chloride pre-irradiation induced significant amelioration in FSH and LH hormone levels on the 7 th day only of experimentation period, and showed non-significant amelioration in testosterone level

Mice with chimeric livers are an improved model for human lipoprotein metabolism.

Science.gov (United States)

Ellis, Ewa C S; Naugler, Willscott Edward; Nauglers, Scott; Parini, Paolo; Mörk, Lisa-Mari; Jorns, Carl; Zemack, Helen; Sandblom, Anita Lövgren; Björkhem, Ingemar; Ericzon, Bo-Göran; Wilson, Elizabeth M; Strom, Stephen C; Grompe, Markus

2013-01-01

Rodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism. FRG [ F ah(-/-) R ag2(-/-)Il2r g (-/-)]) mice were repopulated with primary human hepatocytes. Serum lipoprotein lipid composition and distribution (VLDL, LDL, and HDL) was analyzed by size exclusion chromatography. Bile was analyzed by LC-MS or by GC-MS. RNA expression levels were measured by quantitative RT-PCR. Chimeric mice displayed increased LDL and VLDL fractions and a lower HDL fraction compared to wild type, thus significantly shifting the ratio of LDL/HDL towards a human profile. Bile acid analysis revealed a human-like pattern with high amounts of cholic acid and deoxycholic acid (DCA). Control mice had only taurine-conjugated bile acids as expcted, but highly repopulated mice had glycine-conjugated cholic acid as found in human bile. RNA levels of human genes involved in bile acid synthesis including CYP7A1, and CYP27A1 were significantly upregulated as compared to human control liver. However, administration of recombinant hFGF19 restored human CYP7A1 levels to normal. Humanized-liver mice showed a typical human lipoprotein profile with LDL as the predominant lipoprotein fraction even on a normal diet. The bile acid profile confirmed presence of an intact enterohepatic circulation. Although bile acid synthesis was deregulated in this model, this could be fully normalized by FGF19 administration. Taken together these data indicate that chimeric FRG-mice are a useful new model for human lipoprotein and bile-acid metabolism.

Therapeutic effects of the joint administration of magnesium aspartate and adenosine monophosphate in gamma-irradiated mice

International Nuclear Information System (INIS)

Pospisil, M.; Netikova, J.; Pipalova, I.; Kozubik, A.

1990-01-01

The joint administration of magnesium aspartate and adenosine monophosphate, injected on days 1 to 4 post radiation, has been found to exert stimulatory effects on the recovery of hemopoietic functions in sublethally gamma-irradiated mice. These therapeutical effects were enhanced in animals protected by peroral administration of cystamine. The treatment scheme used did not modify survival of lethally irradiated mice. The therapeutic effects of magnesium aspartate and adenosine monophosphate in sublethally irradiated mice are explained by the stimulatory action of these drugs on the cell adenylate cyclase system, which influences the erythropoietic functions. (author)

Treatment of mice with sepsis following irradiation and trauma with antibiotics and synthetic trehalose dicorynomycolate (S-TDCM)

Energy Technology Data Exchange (ETDEWEB)

Madonna, G.S.; Ledney, G.D.; Moore, M.M.; Elliott, T.B.; Brook, I. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

1991-03-01

Compromise of antimicrobial defenses by irradiation can result in sepsis and death. Additional trauma can further predispose patients to infection and thus increase mortality. We recently showed that injection of synthetic trehalose dicorynomycolate (S-TDCM) significantly augments resistance to infection and increases survival of mice compromised either by whole-body irradiation with gamma radiation or equal mixtures of fission neutron and gamma radiation. In this study, C3H/HeN mice were given a lethal dose of gamma radiation (8.0 Gy) and an open wound (15% total body surface area (TBSA)) 1 hr later while anesthetized. Irradiated/wounded mice became more severely leukopenic and thrombocytopenic than mice exposed to radiation alone, and died from natural wound infection and sepsis within 7 days. S-TDCM given 1 hr postirradiation increased survival of mice exposed to radiation alone. However, this treatment did not increase survival of the irradiated/wounded mice. Systemic antibiotic therapy with gentamicin or ofloxacin for 10 days significantly increased survival time compared with untreated irradiated/wounded mice (p less than 0.01). Combination therapy with topical gentamicin cream and systemic oxacillin increased survival from 0% to 100%. Treatment with S-TDCM combined with the suboptimal treatment of topical and systemic gentamicin increased survival compared with antibiotic treatment alone. These studies demonstrate that post-trauma therapy with S-TDCM and antibiotics augments resistance to infection in immunocompromised mice. The data suggest that therapies which combine stimulation of nonspecific host defense mechanisms with antibiotics may increase survival of irradiated patients inflicted with accidental or surgical trauma.

Treatment of mice with sepsis following irradiation and trauma with antibiotics and synthetic trehalose dicorynomycolate (S-TDCM)

International Nuclear Information System (INIS)

Madonna, G.S.; Ledney, G.D.; Moore, M.M.; Elliott, T.B.; Brook, I.

1991-01-01

Compromise of antimicrobial defenses by irradiation can result in sepsis and death. Additional trauma can further predispose patients to infection and thus increase mortality. We recently showed that injection of synthetic trehalose dicorynomycolate (S-TDCM) significantly augments resistance to infection and increases survival of mice compromised either by whole-body irradiation with gamma radiation or equal mixtures of fission neutron and gamma radiation. In this study, C3H/HeN mice were given a lethal dose of gamma radiation (8.0 Gy) and an open wound (15% total body surface area [TBSA]) 1 hr later while anesthetized. Irradiated/wounded mice became more severely leukopenic and thrombocytopenic than mice exposed to radiation alone, and died from natural wound infection and sepsis within 7 days. S-TDCM given 1 hr postirradiation increased survival of mice exposed to radiation alone. However, this treatment did not increase survival of the irradiated/wounded mice. Systemic antibiotic therapy with gentamicin or ofloxacin for 10 days significantly increased survival time compared with untreated irradiated/wounded mice (p less than 0.01). Combination therapy with topical gentamicin cream and systemic oxacillin increased survival from 0% to 100%. Treatment with S-TDCM combined with the suboptimal treatment of topical and systemic gentamicin increased survival compared with antibiotic treatment alone. These studies demonstrate that post-trauma therapy with S-TDCM and antibiotics augments resistance to infection in immunocompromised mice. The data suggest that therapies which combine stimulation of nonspecific host defense mechanisms with antibiotics may increase survival of irradiated patients inflicted with accidental or surgical trauma

Kinetics of lymphohematopoiesis and leukemia induction in chronically whole-body irradiated RF/J mice

International Nuclear Information System (INIS)

Cain, G.R.; Stitzel, K.A.; Fox, L.A.; Klein, A.K.; Dyck, J.A.; Shimizu, J.A.; Rosenblatt, L.S.

1982-01-01

Lymphohematopoietic progenitor cell populations (bone marrow CFU-GM, splenic CFU-BL) were quantitated in unirradiated and in chronically irradiated (17.5 R/day for 4 weeks) RF/J mice and control CAF 1 mice. RF/J mice were found capable of making substantial numbers of bone marrow CFU-GM but less so than the control strain CAF 1 . Significant strain differences were also seen in ability to form splinic B lymphocyte progenitor cells (CFU-BL). Unirradiated and irradiated RF mice produced over three times as many CFU-BL as CAF 1 mice. Throughout the period of protracted irradiation, followed by a twelve week recovery period, CFU-BL and CFU-GM were depressed less in the RF strain than the CAF 1 strain. This was due to an overcompensatory regenerative response which surpassed homostatic baseline levels. Despite strain and strain x dose differences in CFU-BL and CFU-GM, no significant strain x dose relationships were seen in circulati leukocyte counts. The increased susceptibility of RF mice to radiation-induced leukemia may be related to either inherent depressed regulatory control or the persistence of progenitor cell compartments. An apparent increased cell turnover rate in both CFU-BL and CFU-GM in RF mice following radiation damage may likewise play a contributory role

Protective effects of nelumbo nucifera against {gamma}-irradiation-induced lipid peroxidation in mice urine

Energy Technology Data Exchange (ETDEWEB)

Jeong, Il Yun; Park, Yong Dae; Jin, Caang Hyun; Choi, Dae Seong [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Lee, Hyo Jung [Gwangju Institute of Science and Technology, Gwangju (Korea, Republic of)

2009-12-15

The radioprotective effect of isoquercitrin-abundant fraction (IAF) of N. nucifera Gaertn. Ieaf extract against {gamma}-irradiation-induced oxidative stress was evaluated by the lipid peroxidation-derived aldehydes (LPDAs) as a marker for oxidative risk in mice urine, and the DNA damage using comet assay in RAW 264.7 cells. Mice that were treated with IAF (50 mg/kg) and {gamma}-irradiation showed considerably decreased LPDA levels relative to those that had received {gamma}-irradiation alone. Furthermore, pretreatment with IAF resulted in a significant decrease in the amount of DNA damage in cells. It is demonstrated that pretreatment with IAF of N. nucifera Gaertn. gives protection against irradiation-induced cellular damage.

Relationship between X-ray irradiation and chromosomal damage in bone marrow tissue of mice

International Nuclear Information System (INIS)

Chaubey, R.C.; George, K.P.; Sundaram, K.

1976-01-01

X-ray induced chromosomal damage in bone-marrow tissue of male mice was studied using micronucleus technique. Dose response relationship was evaluated. Male Swiss mice received whole body x-ray irradiation at different doses from 25-1000 rads. Animals were sacrificed at the end of 24 hours, bone-marrow smears were made and stained in May-Grunwald-Giemsa. The preparatians were scored for the following types of aberrations: micronuclei in young erythocytes-polychromatic cells and in the mature erythrocytes-normechromatic cells. A dose dependent increase in the frequency of micronuclei in polychromatic cells up to a dose of 100 rads was observed. In addition the effect of post-irradiation duration on the frequency of micronuclei in polychromatic and normochromatic cells were studied. Male Swiss mice were exposed to 200 rads x-rays and were then sacrificed at different time intervals after irradiation and bone-marrow preparations were made and scored. Maximum polychromatic cells with micronuclei were observed in 24 hours post-irradiated animals, thereafter a decrease in the frequency of polychromatic cells with micronuclei was observed in 40 hours post irradiated animals. (author

Long term low dose rate irradiation causes recovery from type II diabetes and suppression of aging in type II diabetes-prone mice

International Nuclear Information System (INIS)

Namura, T.; Oda, T.

2003-01-01

The effects of low dose rate gamma irradiation on model C57BL/KsJ-db/db mice with Type II diabetes mellitus was investigated. These mice develop Type II diabetes by 10 weeks of age, due to obesity, and are characterized by hyperinsulinemia. A group of 12 female 10-week old mice were irradiated at 0.65 mGy/hr in the low dose rate irradiation facility in the Low Dose Radiation Research Center. The urine glucose levels of all of the mice were strongly positive at the beginning of the irradiation. In the irradiated group, a decrease in the glucose level was observed in three mice, one in the 35th week, another in the 52nd week and the third in the 80th week. No recovery from the diabetes was observed in the 12 mice of non-irradiated control group. There was no systematic change of body weight or consumption of food and drinking water between the irradiated group and the non-irradiated group or between the recovered mice and the non-recovered mice. Survival was better in the irradiated group. The surviving fraction at the age of 90 weeks was 75 % in the irradiated group but only 40 % in the non-irradiated. A marked difference was also observed in the appearance of the coat hair, skin and tail. The irradiated group was in much better condition. Mortality was delayed and the healthy appearance was prolonged in the irradiated mice by about 20-30 weeks compared with the control mice. These results suggest that the low dose irradiation modified the condition of the diabetic mice, leading not only to recovery from diabetes, but also to suppression of the aging process

Stimulation effects of low dose-rate irradiation on pancreatic antioxidant activity in type II diabetes model mice

International Nuclear Information System (INIS)

Nomura, Takaharu; Sakai, Kazuo

2005-01-01

The effects of low dose-rate gamma irradiation on the type II diabetes mellitus were investigated in BKS.Cg-+Lepr db /+Lepr db /Jcl (DB mice). Ten-week-old female DB mice (5 mice in each group) were irradiated with gamma ray at 0.35, 0.70, or 1.2 mGy/hr. During the course of the 12 weeks the glucose level slightly increased with little difference between the irradiated and the non-irradiated groups. The plasma insulin concentration decreased within the first 4 weeks in all groups. The level was kept low in the non-irradiated mice; while the insulin level in the irradiated groups showed a tendency to increase. In the 0.70 mGy/hr group the increase was statistically significant after 12 weeks of irradiation. Total activity of SOD, one of antioxidative enzymes, decreased both in non-irradiated and irradiated groups; however the decrease was less in the irradiated groups, especially 0.70 mGy/hr group. In the 0.70 mGy/hr group Mn-SOD activity, one of the components of total SOD activity, increased after 12-week irradiation. A pathological examination of the pancreas revealed that damage to β cells responsible for the secretion of insulin was much less in the 0.70 mGy/hr group compared to that in the non-irradiated group. These results indicated that the low dose-rate irradiation increase the antioxidative capacity in the pancreas to protect β cells from oxidative damage, and the to increase the insulin level. This mechanism would lead the mice to the recovery from the disease and the prolongation of the life span as is demonstrated in our previous report. (author)

Tanacetum parthenium leaf extract mediated survival protection in lethally irradiated Swiss albino mice

International Nuclear Information System (INIS)

Shetty, Prashanth; Pooja, S.; Suchetha Kumari, N.; Shetty, Jayaram; Peter, Alex John; Jose, Jerish M.

2016-01-01

Search for less-toxic radioprotectors has spurred interest in the development of natural products. In Ayurveda, the traditional medicine, Tanacetum species have been used to treat ailments since ancient times throughout the world. Effects of the administration of different concentrations of Tanacetum parthenium leaf aqueous extract (TPLA), Tanacetum parthenium leaf ethanolic extract (TPLE) were investigated in Swiss albino mice. Mice (20-25 g) were randomly divided into 8 groups of ten animals each. The control group and the radiation group were treated daily with oral administration of saline for 15 days. Each subgroups of TPLA and TPLE were treated with doses of 50, 100 and 250 mg/kg daily for 15 days. On the 15th day, all were irradiated with 10 Gy whole body irradiation. Survival was observed daily up to 30th post-irradiation day. Data were analysed using the Kaplan-Meier survival curves. The significance difference in survival between control, radiation and treatment groups were observed (P < 0.001). Current studies revealed the protective effect of Tanacetum parthenium rendering high survivability in lethally irradiated mice. (author)

Protective effect of hypoxia in the ram testis during single and split-dose X-irradiation

International Nuclear Information System (INIS)

Vliet, J. van; Wensing, C.J.G.; Bootsma, A.L.; Peperzeel, H.A. van; Schipper, J.

1988-01-01

Spertogonial stem-cell survival in the ram was studied after single (6Gy) and split-dose X-irradiation both under normal and hypoxic conditions. Hypoxia was induced by inflation of an occluder implanted around the testicular artery. The occluders were inflated about 10 min before irradiation and deflated immediately after. Stem-cell survival was measured at 5 or 7 weeks after irradiation by determination of the Repopulation Index (RI) in histological testis sections. The RI-values after fractionated irradiation were only half those after single dose irradiation. Hypoxia had a protective effect on the stem-cell survival. After split-dose irradiation under hypoxic conditions two times more stem cells survived than under normal oxic conditions; the RI-values increased from 34% (oxic) to 68% (hypoxic). This effect of hypoxia was also found after single dose irradiation where the RI-values increased from 68% (oxic) to 84% (hypoxic). The development of the epithelium in repopulated tubules was also studied. Under hypoxia, a significantly higher fraction of tubules with complete epithelium was found after single (38 vs. 4%) as well as after split-dose irradiation (12 vs. 0%)

Effect of infection by irradiated Trichinella Spirals larvae on mice and assessment the role of Al bendazole in treating them

International Nuclear Information System (INIS)

Moawad, M.A.F.; Amin, M.M.

2005-01-01

The present study was carried out to investigate the effect of infection with irradiated Trichinella Spiralis larvae on mice and to asses the role of albendazole in treating them. This study included parasitological and histopathological studies on mice infected with irradiated Trichinella Spiralis larvae in comparison with mice infected with non-irradiated Trichinella Spiralis only or with mice treated after infection by albendazole. The obtained data revealed that, in mice infected with irradiated Trichinella Spiralis larvae (50 Krad or 80 Krad), the number and length of worms in the small intestine, as well as, the number of encysted larvae in muscles of mice, especially diaphragm and tongue, were significantly decreased. Also, using al bendazole 24 hours after infection with irradiated larvae lead to high significant decrease in all the previously mentioned parameters

New radiation mitigators to reduce bone marrow death of mice by post-irradiation administration

International Nuclear Information System (INIS)

Anzai, Kazunori

2009-01-01

We have found recently that heat-treated mineral yeast preparations and water-soluble analogs of vitamin E are potent radiation mitigator to reduce bone marrow death of mice by post-irradiation administration. When administered immediately after whole-body X-irradiation (7.5 Gy), both Zn-yeast and γ-tocopherol dimethylglycine ester (TDMG) significantly increased the viability of mice from 0% (control) to more than 90% (treated). Zn-yeast did not inhibit the tumor-regulation by γ-rays but even sensitize the radiation effect in mice xenografts of HeLa cells. (author)

Effect of Zi Gui decoction on immune function in {sup 60}Co {gamma}-ray irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Qiujun, Lu; Shafei, Huang; Xipeng, Zhou; Jiayun, Song; Zhongxiong, Tang [Dept. of Pharmacology, Institute of Radiation Medicine, Beijing (China)

1995-02-01

Zi Gui decoction (ZG), a complex preparation of traditional Chinese herbal medicine, mainly consists of Radix Angelicae and Radix Astragali. The effects of ZG on mitogen induced proliferation IL-1 and -2 production, natural killer (NK) cell activity in {sup 60}Co {gamma}-ray irradiated mice is investigated. After 5 Gy whole body irradiation. mice were treated i.g. with ZG (1.2, 1.8 g/kg/day) for 20 days. An enhancement in Con A- and LPS-induced proliferations of splenocytes from the two dosage groups were observed. There were marked increases in IL-1 activity in peritoneal macrophage culturesa and IL-2 activity in splenocyte cultures from irradiated mice treated with ZG. The two dosage groups also showed significant potentiation of NK cell activity against YAC-1 target cells. The above results indicated that ZG could promote the recovery of immune functions in {gamma}-ray irradiated mice.

Studies on the effects of ionizing radiation and chemotherapeutic agents on hematopoiesis according to the stem-cell kinetics

International Nuclear Information System (INIS)

Hirashima, Kunitake

1975-01-01

The fundamental problem of the effects of ionizing radiation and antineoplastic drugs on hematopoiesis can be explained by the kinetic study on the hematopoietic stem-cell population. Quantitative comparison of a single x-irradiation and a single administration of several antineoplastic drugs on the stem-cell population was performed by the splenic colony-forming method. The repopulation pattern of stem-cells in mice after a single 150 rad irradiation was compared with that after the administration of corresponding dose of cyclophosphamide. It was demonstrated that the additional administration of cyclophosphamide immediately after the x-irradiation significantly accelerated repopulation of the stem-cell compartment. The mechanism of repopulation of the stem-cell compartment after partial irradiation was also studied according to the immigration theory of stem-cells. An in vitro colony-forming technique for the human bone marrow cells was introduced and compared with other assay methods for stem-cells. From the hematological observations of accidentally irradiated patients, it was determined that the thromboelastogram values were regarded as one of the most useful indicators for detecting the earliest recovery sign of the hematopoietic stem-cells. (Evans, J.)

Intratracheal injection of adenovirus containing the human MNSOD transgene protects athymic nude mice from irradiation-induced organizing alveolitis

International Nuclear Information System (INIS)

Epperly, Michael W.; Bray, Jenifer A.; Krager, Stephen; Berry, Luann M.; Gooding, William; Engelhardt, John F.; Zwacka, Ralf; Travis, Elizabeth L.; Greenberger, Joel S.

1999-01-01

Purpose: A dose and volume limiting factor in radiation treatment of thoracic cancer is the development of fibrosis in normal lung. The goal of the present study was to determine whether expression prior to irradiation of a transgene for human manganese superoxide dismutase (MnSOD) or human copper/zinc superoxide dismutase (Cu/ZnSOD) protects against irradiation-induced lung damage in mice. Methods and Materials: Athymic Nude (Nu/J) mice were intratracheally injected with 10 9 plaque-forming units (PFU) of a replication-incompetent mutant adenovirus construct containing the gene for either human MnSOD, human copper/zinc superoxide dismutase (Cu/ZnSOD) or LacZ. Four days later the mice were irradiated to the pulmonary cavity to doses of 850, 900, or 950 cGy. To demonstrate adenoviral infection, nested reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out with primers specific for either human MnSOD or Cu/ZnSOD transgene on freshly explanted lung, trachea, or alveolar type II cells, and immunohistochemistry was used to measure LacZ expression. RNA was extracted on day 0, 1, 4, or 7 after 850 cGy of irradiation from lungs of mice that had previously received adenovirus or had no treatment. Slot blot analysis was performed to quantitate RNA expression for IL-1, tumor necrosis factor (TNF)-α, TGF-β, MnSOD, or Cu/ZnSOD. Lung tissue was explanted and tested for biochemical activity of MnSOD or Cu/ZnSOD after adenovirus injection. Other mice were sacrificed 132 days after irradiation, lungs excised, frozen in OCT, (polyvinyl alcohol, polyethylene glycol mixture) sectioned, H and E stained, and evaluated for percent of the lung demonstrating organizing alveolitis. Results: Mice injected intratracheally with adenovirus containing the gene for human MnSOD had significantly reduced chronic lung irradiation damage following 950 cGy, compared to control mice or mice injected with adenovirus containing the gene for human Cu/ZnSOD or LacZ. Immunohistochemistry

Alpha-methyl-homocysteine thiolactone protects lung of BALB/c mice irradiated with 6 Gy

International Nuclear Information System (INIS)

Lubec, G.; Tichatschek, E.; Foltinova, J.; Leplawy, T.; Mallinger, R.; Getoff, N.

1996-01-01

The radiation protective activity of intaperitoneally administered alpha-methyl-homocysteine thiolactone (α-MHCTL); 100 mg/kg body weight) in female BALB/c mice and such treated with cysteine treated (100 mg/kg body weight), using unirradiated and placebo treated irradiated mice were tested as controls. 6Gy whole body irradiated was applied and after a period of three weeks the animals were sacrificed and lungs were taken for morphometry and the determination of o-tyrosine. Septal areas were highest in the irradiated, placebo treated mice (68.67 + 9.82% septal area to total area) and lowest in the α-MHCTL treated irradiated mice (55.67 + 11.29%), significant at the p < 0.05 level. Morphometric data were accompanied by highest levels of o-tyrosine, a reliable parameter for OH-attack, in the irradiated, placebo treated group with 1.87 + 0.40 μM/g lung tissue and 0.32 + 0.13 μM/g lung tissue in the αMHCTL treated group; the statistical difference was significant. Significant radiation protection in the mammalian system at the morphological and biochemical level were found. The potent effect could be explained by the influence of alpha-alkylation in homocysteine thiolactone (HCTL) which renders amino acids unmetabolizeable, nontoxic, increases lipophilicity and therefore improving permeability through membranes. The present report confirms morphological data on the radiation protective activity of this interesting thiol compound. (Author)

Effects of low dose rate irradiation on induction of myeloid leukemia in mice

International Nuclear Information System (INIS)

Furuse, Takeshi

1999-01-01

We investigated the induction of myeloid leukemia and other kinds of neoplasias in C3H male mice irradiated at several dose rate levels. We compared the incidence of neoplasias among these groups, obtained dose and dose rate effectiveness factors (DDREF) for myeloid leukemia. C3H/He male mice were exposed to whole body gamma-ray irradiation at 8 weeks of age. All mice were maintained for their entire life span and teh pathologically examined after their death. Radiation at a high dose-rate of 882 mGy/min (group H), a medium dose-rate of 95.6 mGy/min (group M), and low dose-rates of 0.298 mGy/min (group L-A), 0.067 mGy/min (group L-B) or 0.016 mGy/min (group L-C) were delivered from 137 Cs sources. The mice in group L were irradiated continuously for 22 hours daily up to total doses of 1, 2, 3, 4, 10 Gy over a period of 3 days to 200 days. As for the induction of neoplasias, myeloid leukemia developed significantly more frequently in irradiated groups than in unirradiated groups. The time distribution of mice dying from myeloid leukemia did not show a difference between groups H and L. The incidence of myeloid leukemia showed a greater increase in the high dose-rate groups than in the low and medium dose-rate groups in the dose range over 2 Gy, it also showed significant increases in the groups irradiated with 1 Gy of various dose rate, but the difference between these groups was not clear. These dose effect curves had their highest values on each curve at about 3 Gy. We obtained DDREF values of 2-3 by linear fittings for their dose response curves of dose ranges in which leukemia incidences were increasing. (author)

Survival of mouse testicular stem cells after γ or neutron irradiation

International Nuclear Information System (INIS)

Lu, C.C.; Meistrich, M.L.; Thames, H.D. Jr.

1980-01-01

The survival of mouse testicular stem cells after γ or neutron irradiation was measured by counts of repopulated tubular cross sections and by the numbers of differentiated spermatogenic cells produced. The numbers of such cells were determined either by sperm head counts of the X-isozyme of lactate dehydrogenase enzyme levels. Qualitatively similar results were obtained with all three assays. The results have confirmed that, with C3H mice, stem-cell survival is higher when the γ-radiation dose is fractionated by a 24-h interval. Single-dose γ-radiaton survival curves for the stem cell had large shoulders and also showed the presence of a radioresistant subpopulation which predominated after doses greater than 600 rad. Part of the shoulder must have resulted from repair of sublethal damage since neutron irradiation produced survival curves with smaller shoulders. The relative biological effectiveness for stem-cell killing for these neutrons (mean energy, 22 MeV) varied from about 2.9 at 10 rad of γ radiation to 2.2 at 600 rad

Therapy of infections in mice irradiated in mixed neutron/photon fields and inflicted with wound trauma: a review of current work.

Science.gov (United States)

Ledney, G D; Madonna, G S; Elliott, T B; Moore, M M; Jackson, W E

1991-10-01

When host antimicrobial defenses are severely compromised by radiation or trauma in conjunction with radiation, death from sepsis results. To evaluate therapies for sepsis in radiation casualties, we developed models of acquired and induced bacterial infections in irradiated and irradiated-wounded mice. Animals were exposed to either a mixed radiation field of equal proportions of neutrons and gamma rays (n/gamma = 1) from a TRIGA reactor or pure gamma rays from 60[Co sources. Skin wounds (15% of total body surface area) were inflicted under methoxyflurane anesthesia 1 h after irradiation. In all mice, wounding after irradiation decreased resistance to infection. Treatments with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) before or after mixed neutron-gamma irradiation or gamma irradiation increased survival. Therapy with S-TDCM for mice irradiated with either a mixed field or gamma rays increased resistance to Klebsiella pneumoniae-induced infections. Combined therapy with S-TDCM and ceftriaxone for K. pneumoniae infections in mice exposed to a mixed radiation field or to gamma rays was more effective than single-agent therapy. In all irradiated-wounded mice, single therapy of acquired infections with an antibiotic or S-TDCM did not increase survival. Survival of irradiated-wounded mice after topical application of gentamicin sulfate cream suggested that bacteria colonizing the wound disseminated systemically in untreated irradiated mice, resulting in death from sepsis. In lethal models of acquired infections in irradiated-wounded mice, significant increases in survival were achieved when systemic treatments with S-TDCM or gentamicin were combined with topical treatments of gentamicin cream. Therapies for sepsis in all mice exposed to a mixed field were less effective than in mice exposed to gamma rays. Nonetheless, the data show a principle by which successful therapy may be provided to individuals receiving tissue trauma in conjunction with

Some mechanisms of disturbances and recovery of T-lymphocyte migratory properties in irradiated mice

International Nuclear Information System (INIS)

Anokhin, G.N.; Yarilin, A.A.

1984-01-01

Migration of 51 Cr-labelled T cells from irradiated mice into lymph nodes of syngeneic unirradiated recipients decreased in a dose-dependent fashion. Influx of labelled T cells between 4 and 24 hr after injection (secondary migration) is more radiosensitive than lymph-node migration of T cells in the first 4 hr (primary migration). Treatment of T cells from irradiated mice in vitro with Con A or with trypsin does not enhance radiation-induced alteration of their migratory properties, but irradiation enhances the effects of Con A and trypsin on T-cell migration. Recovery of primary migration of irradiated T cells is completed 3 months after irradiation; it is probably caused by T-cell renewal. The defect of T-cell secondary migration is more stable: it remains 6 months after irradiation in a dose of 4 gy. Post-irradiation defects of the T-cell differentiation process as a cause of long-lasting alteration of T-cell secondary migration are discussed. (author)

Effects of cadmium on haemopoiesis in irradiated and non-irradiated mice: 2. Relationship to the number of circulating blood cells and haemopoiesis

International Nuclear Information System (INIS)

Mackova, N.O.; Lenikova, S.; Fedorocko, P.; Brezani, P.; Fedorockova, A.

1996-01-01

The effect of administration of cadmium alone in non-irradiated mice as well as the effect of pre-irradiation administration of cadmium on the reparation processes were investigated in mice irradiated with a dose of 7.5 Gy. The pre-irradiation administration of cadmium accelerated the reparation process in the bone marrow and spleen as well as the number of leukocytes and thrombocytes in the peripheral blood. The administration of cadmium alone caused a temporary weight decrease of the thymus and reduced the number of erythrocytes, reticulocytes, and the haemoglobin values in the peripheral blood. The temporary rapid increase in the number of leukocytes on the 21st day after cadmium administration was investigated. 3 figs., 28 refs

Treatment of wound sepsis in irradiated mice

International Nuclear Information System (INIS)

Brook, I.; Elliott, T.B.

1989-01-01

The local and systemic effect of penicillin therapy, supplemented by immunoglobulins, and pentoxifylline on wounds infected by Staphylococcus aureus was evaluated in mice irradiated with 6.5 Gy 60 Co γ-rays. Treatment with 62.5 mg/kg penicillin-G was administered for 10 days. Numbers of bacteria were significantly reduced from 7.3 (± 0.3) to 5.3 (± 0.4) log 10 CFU/mg ± muscle in treated animals. Administration of immunoglobulin G i.v. or pentoxifylline i.p. alone, or in addition to penicillin-G, did not further reduce the number of bacteria. Increase in the dose of penicillin to 250 mg/kg decreased the number of bacteria more than 62.5 mg/kg. Bacteria were recovered from spleens and/or livers of all 13 untreated mice, and only in six of the 13 penicillin-treated mice (P<0.05). Penicillin therapy reduced the systemic spread of S. aureus. (author)

Evaluation of the role of both irradiation and albenazole in the control of hydatidosis in mice

International Nuclear Information System (INIS)

Moawad, M.A.F.

2005-01-01

The present study mainly aims to evaluate the role of irradiated hydatid cysts and treatment by albendazole on the control of hydatidosis. Eighty male mice were divided equally into four groups. The first group was infected with normal non-irradiated viable particular's. The second group was infected with non-irradiated particular's then treated with al bendazole at a dose of 0.52 mg/kg body weight. The third and fourth groups were infected with 45 Krad and 65 Krad irradiated protoscolices, respectively. Each animal was received 2000 protoscolices by intraperitoneal injection. After 12 and 16 weeks post-infection, parasitological and enzymatic aspects of the mice were examined. The group infected with irradiated protoscolices and the group infected with non-irradiated protoscolices then treated with albendazole showed significant decrease in the number of the developing cysts in both of the liver and omentum. Such decrease was more pronounced with higher dose level of gamma irradiation as compared to the control group (non-irradiated protoscolices). Furthermore, there were significant decreases in the enzyme levels of the liver of mice (y-GT, ALP, ALT and AST) in groups given irradiated viable protoscolices and group given albendazole drug after infection compared to groups given non-irradiated viable protoscolices (control group)

Modification of survival and hematopoiesis in mice by tocopherol injection following irradiation

International Nuclear Information System (INIS)

Bichay, T.J.E.; Roy, R.M.

1986-01-01

The LD 50/30 of CD-1-female mice increased from 6.6 Gy to 7.0 Gy when 2.5 mg of dl-α-tocopherol was injected immediately post irradiation. Increased survival was associated with increased numbers of hematopoietic colony forming units (CFU). Endogeneous spleen colonies were found in greater numbers in the tocopherol-treated mice after irradiation. The vitamin, however, must be injected within five hours following irradiation to have this effect. The increased numbers of CFU in tocopherol-treated mice may be due to a stimulation of recovery of repair processes. Split-dose studies suggest that most repair of sublethal damage in hematopoietic stem cells take place within seven and nine hours following irradiation. Tocopherol injection appears to enhance the recovery manifested in the split-dose assay. There is also evidence that tocopherol-treatment caused an earlier onset of mitotic activity in CFU after irradiation. The increased number of spleen colonies in tocopherol-injected mice is not due to an altered CFU seeding efficiency associated with an altered spleen microenvironment. Tocopherol injection did not affect the shoulder of the stem cell survival curve using exogenous spleen colony assays of bone marrow-derived or spleen-derived hematopoietic stem cells. There appears to be a decrease in D 0 in the higher dose region (4.3 Gy) of the bone marrow exogenous SCA survival curves for the vehicle-injected and the non-injected groups; however, the tocopherol-injected group showed no evidence of change in radiosensitivity up to the highest dose used (5.0 Gy). Data may be interpreted to suggest that the therapeutic effect of tocopherol may involve repair of hematopoietic stem cell damage in the higher dose range of bone marrow syndrome. (orig.) [de

Targeted genome editing in human repopulating haematopoietic stem cells

NARCIS (Netherlands)

P. Genovese (Pietro); G. Schiroli (Giulia); G. Escobar (Giulia); T. Di Tomaso (Tiziano); C. Firrito (Claudia); A. Calabria (Andrea); D. Moi (Davide); R. Mazzieri (Roberta); C. Bonini (Chiara); M.V. Holmes (Michael); P.D. Gregory (Philip); M. van der Burg (Mirjam); B. Gentner (Bernhard); E. Montini (Eugenio); A. Lombardo (Angelo); L. Naldini (Luigi)

2014-01-01

textabstractTargeted genome editing by artificial nucleases has brought the goal of site-specific transgene integration and gene correction within the reach of gene therapy. However, its application to long-term repopulating haematopoietic stem cells (HSCs) has remained elusive. Here we show that

Augmentation of transfer of experimental autoimmune thyroiditis (EAT) in mice by irradiation of recipients

International Nuclear Information System (INIS)

Williams, W.V.; Kyriakos, M.; Sharp, G.C.; Braley-Mullen, H.

1987-01-01

Experimental autoimmune thyroiditis (EAT) can be adoptively transferred to normal syngeneic recipients using spleen cells from susceptible strains of mice primed in vivo with mouse thyroglobulin (MTg) and lipopolysaccharide (LPS) following in vitro activation of spleen cells by culture with MTg. Irradiation of recipient animals markedly augments the severity of thyroiditis induced in this system. Irradiation of recipients does not alter the time course of the development of thyroiditis, nor does it alter the requirement for both in vivo priming and in vitro activation of spleen cells for the development of EAT. Spleen cells from EAT-resistant strains of mice (e.g., Balb/c) do not induce EAT in irradiated recipients. Irradiated recipients develop significant levels of anti-MTg antibodies while unirradiated recipients have little detectable antibody response. The augmenting effect of irradiation can be substantially reversed by transferring naive spleen cells to recipients prior to the transfer of MTg/LPS-primed in vitro-activated spleen cells. In addition athymic CBA/Tufts nude mice develop more severe EAT than CBA/Tufts nude/+ littermates following transfer of activated CBA/J spleen cells. These data suggest that natural suppressor cells may regulate the development of EAT at the effector cell level

γ-irradiation-induced mortality: protective effect of protease inhibitors in chickens and mice

International Nuclear Information System (INIS)

Palladino, M.A.; Galton, J.E.; Troll, W.; Thorbecke, G.J.

1982-01-01

Chickens (Gallus domesticus) were protected from the acute γ-irradiation-induced mortality (within 24 hours) by the proteolytic enzyme inhibitors, soy-bean trypsin inhibitor (SBTI), lima bean inhibitor (LBTI), antipain, α-N-benzoyl-L-arginine ethyl ester HCl (BAEE), trasylol, and leupeptin. Several other enzyme inhibitors, p-tosyl-L-arginine methyl ester HCl (TAME), α-tosyl-lysyl-chloromethyl ketone HCl (TLCK) and epsilon-amino caproic acid (EACA), did not protect. EACA even increased the mortality caused by γ-irradiation. The pattern of protective enzyme inhibitors suggests involvement of a kallikrein-like enzyme. SBTI and antipain also protected against low range lethal γ-irradiation exposures, 690 R in BALB/c and 880 R in SJL/J mice. It is suggested that enhanced vascular permeability, which in chickens is known to be the cause of the irradiation mortality during the first 24 hours, may also contribute to the mortality in mice during the first week after irradiation. (author)

Vitamin E-deficiency did not exacerbate partial skin reactions in mice locally irradiated with X-rays

International Nuclear Information System (INIS)

Chi, C.; Hayashi, Daisuke; Nemoto, Masato; Nyui, Minako; Anzai, Kazunori; Urano, Shiro

2011-01-01

We previously showed that free radicals and oxidative stress are involved in radiation-induced skin reactions. Since vitamin E (VE) is a particularly important lipophilic antioxidant, VE-deficient mice were used to examine its effects on radiation-induced skin damage. The VE content of the skin was reduced to one fourth of levels of normal mice. Neither the time of onset nor the extent of the reactions quantified with a scoring system differed between normal and VE-deficient mice after local X-irradiation (50 Gy). Similarly, there was no difference in the levels of the ascorbyl radical between the groups, although they were higher in irradiated skin than non-irradiated skin. X-irradiation increased the amount of Bax protein in the skin of normal mice both in the latent and acute inflammatory stages, time- and dose-dependently. The increase was associated with an increase in cytochrome c in the cytosolic fraction, indicating that apoptosis was also promoted by the irradiation. The increase in Bax protein correlated well with the thickness of the skin. Although a deficiency in VE should lower resistance to free radicals in the mitochondrial membrane and thus enhance radiation-induced Bax expression and apoptosis, it actually attenuated the increase in Bax protein caused by irradiation. (author)

Physiology of B cells in mice with X-linked immunodeficiency (xid). III. Disappearance of xid B cells in double bone marrow chimeras

International Nuclear Information System (INIS)

Sprent, J.; Bruce, J.

1984-01-01

Evidence is presented that B cells from mice with X-linked immunodeficiency (xid) differentiate at a slower rate than normal B cells. This conclusion stems from studies in which (B6 X CBA/J)F1 mice were heavily irradiated (1,000 rads) and reconstituted with a mixture of T-depleted marrow cells taken from (a) nondefective B6 mice (H-2b) and (b) xid CBA/N or nondefective CBA/Ca mice (both H-2k). With transfer of CBA/Ca plus B6 marrow cells, the irradiated recipients become repopulated with B cells derived from both parental marrow sources; except for an early imbalance (probably reflecting Hh resistance), the degree of chimerism remained relatively stable over a period of more than 6 months. Very different results occurred with transfer of a mixture of xid CBA/N and normal B6 marrow. Within the first 2 months after marrow reconstitution, a low but significant proportion of the B cells in both spleen and lymph nodes were of CBA/N origin. Thereafter the proportion of these cells fell progressively, and by 6-9 months virtually all of the B cells were of B6 origin. This gradual decline in CBA/N-derived cells did not apply to other cell types, i.e., T cells or pluripotential stem cells. Analogous results were obtained with transfer of CBA/N vs. CBA/Ca marrow cells into sublethally irradiated (750 rads) (CBA/N X DBA/2)F1 male vs. female mice. For example, CBA/N-marrow derived B cells differentiated effectively and survived for long periods in F1 male mice (xid----xid) but not in F1 female mice (xid----normal). The finding that xid B cells eventually disappear in the presence of normal B cells strengthens the view that xid B cells are an abnormal population not represented in normal mice

Effects of perfluorochemical emulsion on the timing of administration and irradiation in tumor bearing mice

International Nuclear Information System (INIS)

Hishikawa-Itoh, Youko; Ayakawa, Yoshio; Miyata, Nobuki

1988-01-01

Perfluorochemical content was examined periodically, in blood, tumor and some organs using gas chromatography, after Fluosol-DA saline 20 % (FDAS) was injected into LLC bearing mice. The blood half-life of FDAS in LLC bearing mice was 3.76 hrs (5 ml/kg injection) or 6.15 hrs (20 ml/kg injection) respectively, and FDAS almost disapeared from the blood after about 2 days (5 ml/kg) and 3 days (20 ml/kg) of FDAS-injection. Most of FDAS was accumulated into spleen and the liver. FDAS accumulation into the tumor tissue was 1 ∼ 6 % of injected-FDAS dose and the peak of FDAS accumulation was 1 ∼ 3 days after injection. The timing of FDAS-injection and irradiation in tumor bearing mice determined according to the results above (half-life and accumulation of FDAS in tumor). FDAS (5, 10, 20 ml/kg) was injected to LLC-bearing mice on 3, 2, 1 and 0 day before irradiation and they were irradiated 15 Gray under oxygen-breathing, respectively. FDAS-injected groups before irradiation (3, 2, 1 day before, respectively) showed a tendency of tumor growth delay, but didn't show significant difference as compared with oxygen-breathing group without FDAS, because they had not enough effective FDAS content in the blood. Although the FDAS-injected groups just before irradiation significantly showed the delay of tumor growth. These results demonstrate that oxygen and FDAS existing in the blood injected just before irradiation effectively delay tumor growth in which the lowest effective dose is 5 ml/kg. In the case of clinical application of FDAS, FDAS may be most effective, when administrated just before irradiation in every fractionated irradiation. (author)

Effects of genistein following fractionated lung irradiation in mice

International Nuclear Information System (INIS)

Para, Andrea E.; Bezjak, Andrea; Yeung, Ivan W.T.; Van Dyk, Jake; Hill, Richard P.

2009-01-01

Background and purpose: This study investigated protection of lung injury by genistein following fractionated doses of radiation and its effect on tumor response. Material and methods: C3H/HeJ mice were irradiated (100 kVp X-rays) with 9 fractions of 3.1 Gy over 30 days (approximately equivalent to 10 Gy single dose) and were maintained on a genistein diet (∼10 mg/kg). Damage was assessed over 28 weeks in lung cells by a cytokinesis block micronucleus (MN) assay and by changes in breathing rate and histology. Tumor protection was assessed using a colony assay to determine cell survival following in situ irradiation of small lung nodules (KHT fibrosarcoma). Results: Genistein caused about a 50% reduction in the MN damage observed during the fractionated radiation treatment and this damage continued to decrease at later times to background levels by 16 weeks. In mice not receiving Genistein MN levels remained well above background out to 28 weeks after irradiation. Genistein reduced macrophage accumulation by 22% and reduced collagen deposition by 28%. There was minimal protection against increases in breathing rate or severe morbidity during pneumonitis. No tumor protection by genistein treatment was observed. Conclusions: Genistein at the dose levels used in this study partially reduced the extent of fibrosis developing in mouse lung caused by irradiation but gave minimal protection against pneumonitis. There was no evidence that genistein caused protection of small tumors growing in the lung.

Characteristics and function of bone marrow stromal adherent cells in normal and irradiated mice and guinea pigs

Energy Technology Data Exchange (ETDEWEB)

Changyu, Zheng; Ji, Liu; Xiaoying, Bi

1986-04-01

It has been shown from cytochemical and other characteristic studies of bone marrow stromal cells in CFU-F that there are seven types of stromal cells in the stromal adherent cell layer of normal and irradiated C/sub 57/ mice whereas there are only six types in guinea pigs. On the other hand, a radioresistant cell subtype appears in adherent layer after irradiation of both C/sub 57/ mice and guinea pig since the supernatant of cultured CFU-F of the normal and irradiated C/sub 57/ mice can stimulate production of CFU-Gm. It is justifiable that the bone marrow stromal adherent cells of the C/sub 57/ mice could produce CSF.

Effect of intestinal microflora on the survival time of mice exposed to lethal whole-body. gamma. irradiation

Energy Technology Data Exchange (ETDEWEB)

Onoue, M.; Uchida, K.; Yokokura, T.; Takahashi, T.; Mutai, M.

1981-11-01

The effect of intestinal microflora on the survival time of mice exposed to 2-kR whole-body ..gamma.. irradiation was studied using germfree, monoassociated, and conventionalized ICR mice. The germfree mice were monoassociated with 1 of 11 bacterial strains, which were isolated from the fresh feces of conventional mice, 2 weeks prior to irradiation. All mice died within 3 weeks after irradiation. Monoassociation with Fusobacterium sp., Streptococcus faecalis, Escherichia coli, or Pseudomonas sp. significantly reduced the mean survival time compared to that of germfree mice. In contrast, monoassociation with Clostridium sp., Bifidobacterium pseudolongum, or Lactobacillus acidophilus significantly prolonged the mean survival time compared to that of germfree mice. This suggests that the latter organisms may perform some activity to protect the mice from radiation injury. In this histopathological autopsy examination, the main lesions were hypocellularity in hematopoietic organs and hemorrhage in various organs. Neither karyorrhexis nor desquamation of intestinal mucosal cells was observed in any mice. From these observations, it is suggested that the death of these mice was related to hematopoietic damage. Bacterial invasion into various organs was observed in conventionalized and Pseudomonas-, E. coli-, or S. faecalis-monoassociated mice but not in Clostridium-, B. pseudolongum-, L. acidophilus-, or Fusobacterium-monoassociated mice.

Effect of intestinal microflora on the survival time of mice exposed to lethal whole-body γ irradiation

International Nuclear Information System (INIS)

Onoue, M.; Uchida, K.; Yokokura, T.; Takahashi, T.; Mutai, M.

1981-01-01

The effect of intestinal microflora on the survival time of mice exposed to 2-kR whole-body γ irradiation was studied using germfree, monoassociated, and conventionalized ICR mice. The germfree mice were monoassociated with 1 of 11 bacterial strains, which were isolated from the fresh feces of conventional mice, 2 weeks prior to irradiation. All mice died within 3 weeks after irradiation. Monoassociation with Fusobacterium sp., Streptococcus faecalis, Escherichia coli, or Pseudomonas sp. significantly reduced the mean survival time compared to that of germfree mice. In contrast, monoassociation with Clostridium sp., Bifidobacterium pseudolongum, or Lactobacillus acidophilus significantly prolonged the mean survival time compared to that of germfree mice. This suggests that the latter organisms may perform some activity to protect the mice from radiation injury. In this histopathological autopsy examination, the main lesions were hypocellularity in hematopoietic organs and hemorrhage in various organs. Neither karyorrhexis nor desquamation of intestinal mucosal cells was observed in any mice. From these observations, it is suggested that the death of these mice was related to hematopoietic damage. Bacterial invasion into various organs was observed in conventionalized and Pseudomonas-, E. coli-, or S. faecalis-monoassociated mice but not in Clostridium-, B. pseudolongum-, L. acidophilus-, or Fusobacterium-monoassociated mice

Recovery and radio-resistance in mice after external irradiation

International Nuclear Information System (INIS)

Le Guillou, S.

1965-01-01

The author presents a literature study concerning recovery from external irradiation and an analysis of experimental data (which appear to suggest the idea of a radio-resistance in animals), as well as the hypotheses put forward for explaining this phenomenon. The author then describes an experiment carried out on mice whose LD 50/30 days increased from 1005 to 1380 rads and for which it was shown that an increase occurs in the number of certain anti-bodies circulating after a low dose of γ irradiation. (author) [fr

Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation.

Science.gov (United States)

Kahn, Joy; Byk, Tamara; Jansson-Sjostrand, Lottie; Petit, Isabelle; Shivtiel, Shoham; Nagler, Arnon; Hardan, Izhar; Deutsch, Varda; Gazit, Zulma; Gazit, Dan; Karlsson, Stefan; Lapidot, Tsvee

2004-04-15

A major limitation to clinical stem cell-mediated gene therapy protocols is the low levels of engraftment by transduced progenitors. We report that CXCR4 overexpression on human CD34+ progenitors using a lentiviral gene transfer technique helped navigate these cells to the murine bone marrow and spleen in response to stromal-derived factor 1 (SDF-1) signaling. Cells overexpressing CXCR4 exhibited significant increases in SDF-1-mediated chemotaxis and actin polymerization compared with control cells. A major advantage of CXCR4 overexpression was demonstrated by the ability of transduced CD34+ cells to respond to lower, physiologic levels of SDF-1 when compared to control cells, leading to improved SDF-1-induced migration and proliferation/survival, and finally resulting in significantly higher levels of in vivo repopulation of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice including primitive CD34+/CD38(-/low) cells. Importantly, no cellular transformation was observed following transduction with the CXCR4 vector. Unexpectedly, we documented lack of receptor internalization in response to high levels of SDF-1, which can also contribute to increased migration and proliferation by the transduced CD34+ cells. Our results suggest CXCR4 overexpression for improved definitive human stem cell motility, retention, and multilineage repopulation, which could be beneficial for in vivo navigation and expansion of hematopoietic progenitors.

Thy-1+ dendritic cells in murine epidermis are bone marrow-derived

International Nuclear Information System (INIS)

Breathnach, S.M.; Katz, S.I.

1984-01-01

Thy-1+, Ly-5+ dendritic cells have recently been described as a resident cell population in murine epidermis, but their ontogeny and function are unknown. The origin and turnover of epidermal Thy-1+ cells utilizing chimeric mice were investigated. Lethally x-irradiated AKR/J (Thy-1.1+) and AKR/Cum (Thy-1.2+) mice were reconstituted with allogeneic bone marrow cells with or without thymocytes from congenic AKR/Cum or AKR/J mice, respectively. The density of residual indigenous Thy-1.1+ cells in AKR/J chimeras and Thy-1.2+ cells in AKR/Cum chimeras was substantially reduced following x-irradiation, as determined by immunofluorescence staining of epidermal sheets. Epidermal repopulation by allogeneic Thy-1+ dendritic epidermal cells was first observed at 5 weeks in AKR/J chimeras and at 7 weeks in AKR/Cum chimeras and progressed slowly. Repopulation was not enhanced by increasing the number of allogeneic bone marrow cells injected from 2 X 10(7) to 10(8) cells or by the addition of 8 X 10(7) allogeneic thymocytes to the donor inoculate. Epidermal repopulation by allogeneic Thy-1.2+ cells was not seen in AKR/J mice reconstituted with syngeneic bone marrow cells and allogeneic Thy-1.2+ AKR/Cum thymocytes. Taken together, these results indicate that Thy-1+ dendritic epidermal cells are derived from the bone marrow and suggest that they are not related to conventional peripheral T-lymphocytes

The effects of gut commensal bacteria depletion on mice exposed to acute lethal irradiation

International Nuclear Information System (INIS)

Hou Bing; Xu Zhiwei; Zhang Chenggang

2007-01-01

The prevention and management of bacterial infection are the mainstays of therapies for irradiation victims. However, worries about adverse effects arise from gut commensal flora depletion owing to the broad-spectrum antibiotics treatment. In the present study, we investigated the effects of gut bacteria depletion on the mice receiving total-body irradiation (TBI) at a single dose of 12 Gy. One group of mice was merely exposed to TBI but was free of antibiotic treatment throughout the experiment, while the other two groups of mice were additionally given broad-spectrum antibiotics, either from 2 weeks before or immediately after irradiation. The survival time of each animal in each group was recorded for analysis. Results showed that the mean survival time of mice was longest in the group without antibiotic treatment and shortest in the group treated with broad-spectrum antibiotics from 2 weeks before TBI. In conclusion, our data suggested that depletion of gut commensal bacteria with broad-spectrum antibiotics seemed deleterious for mammals receiving lethal TBI. (author)

Immuno-enhancement in tumor-bearing mice induced by whole body X-irradiation with 75 mGy

International Nuclear Information System (INIS)

Zhang Ying; Li Xiuyi; Gong Shouliang; Liu Shuzheng

2000-01-01

Objective: In present study the authors observed the effect of whole body irradiation (WBI) with 75 mGy X-rays on the immune function of tumor-bearing mice. Methods: Lewis lung carcinoma cells were implanted into the right thigh muscle of C57BL/6J mice. Ten days after tumor implantation, the tumor-bearing mice were administrated with 75 mGy X-rays WBI, then the mice were sacrificed 18 h after irradiation to detect the immune parameters including the spontaneous proliferation of thymocytes, the proliferative response of splenocytes to ConA and LPS, the cytotoxic activities of specific cytotoxic lymphocytes (CTL) and natural killer cells (NK), as well as lymphokine activated killer cells (LAK) in spleen. The methods the authors used were 3 H-TdR incorporation or release assay. Results: the immune parameters of exposed tumor-bearing mice were much higher than those of sham-irradiated tumor-bearing mice (P<0.01). Conclusion: These results suggested that low dose radiation (LDR) could enhance the immune function of tumor-bearing mice, which might be of practical significance in the prevention and therapy of cancer

Protective effect of yeast β-glucan on immune system of mice irradiated by carbon ions

International Nuclear Information System (INIS)

Wang Ying; Lu Dong; Wei Wei; Jing Xigang; Wang Jufang; Li Wenjian

2012-01-01

Abstract. To detect Yeast β-glucan's protective effect on mice's immune system after C ion beam radiation, mice were used as the test model. We observed the weight, hair color and behavior of mice everyday within a 7 d period of time after irradiation. Meanwhile, the content of white blood cell, on the 2nd and 7th day after irradiation was detected. We detected the thymus and spleen SOD, GSH-PX activity and MDA content of the mice on the 8th day. The results showed that yeast β-glucan could reduce the rapid weight loss of mice, increase white blood cell content, increase thymus and spleen SOD, GSH-PX activity, decrease MDA content of thymus and spleen. These results indicate that yeast 13-glucan can protect mice's immune system against C ion beam radiation damage. (authors)

Radioprotective effect of Ganoderma lucidum (Leyss. ex. Fr. ) Karst after X-ray irradiation in mice

Energy Technology Data Exchange (ETDEWEB)

Hsu, H.Y.; Lian, S.L.; Lin, C.C. (Kaohsiung Medical College (Taiwan))

1990-01-01

Six to seven week old male mice of ICR strain were exposed to 500 or 650 cGy of X-ray during experiments to determine if Ganoderma lucidum could be a factor in modification of radiation damage. Continuous intraperitoneal injection of the extract from Ganoderma lucidum before or after irradiation of 500 and 650 cGy of X-ray was found to improve the 30-day survival fractions of ICR mice, but wasn't significant by statistical analysis. The administration also enhanced the recoveries of the body weights and increased the recovery of hemograms of irradiated mice from radiation damage by injecting before or after radiation exposure, especially for the treatment of 500 cGy irradiation. The 10-day CFUs was significantly higher for Ganoderma lucidum treated groups than for untreated groups. However, the differences of radioprotective effect between the X-ray irradiated groups with Ganoderma lucidum pretreated and post-treated were not significant (p greater than 0.05).

Radioprotective effect of Ganoderma lucidum (Leyss. ex. Fr.) Karst after X-ray irradiation in mice

International Nuclear Information System (INIS)

Hsu, H.Y.; Lian, S.L.; Lin, C.C.

1990-01-01

Six to seven week old male mice of ICR strain were exposed to 500 or 650 cGy of X-ray during experiments to determine if Ganoderma lucidum could be a factor in modification of radiation damage. Continuous intraperitoneal injection of the extract from Ganoderma lucidum before or after irradiation of 500 and 650 cGy of X-ray was found to improve the 30-day survival fractions of ICR mice, but wasn't significant by statistical analysis. The administration also enhanced the recoveries of the body weights and increased the recovery of hemograms of irradiated mice from radiation damage by injecting before or after radiation exposure, especially for the treatment of 500 cGy irradiation. The 10-day CFUs was significantly higher for Ganoderma lucidum treated groups than for untreated groups. However, the differences of radioprotective effect between the X-ray irradiated groups with Ganoderma lucidum pretreated and post-treated were not significant (p greater than 0.05)

Effect of cetuximab and fractionated irradiation on tumour micro-environment.

NARCIS (Netherlands)

Santiago, A.; Eicheler, W.; Bussink, J.; Rijken, P.F.J.W.; Yaromina, A.; Beuthien-Baumann, B.; Kogel, A.J. van der; Baumann, M.; Krause, M.

2010-01-01

BACKGROUND AND PURPOSE: Previous experiments have shown that application of the anti-EGFR monoclonal antibody C225 (cetuximab) improves local tumour control after irradiation in FaDu human squamous cell carcinoma (hSCC) due to the combined effect of decreased repopulation and improved reoxygenation.

Analysis of proteomic changes of the serum of irradiated mice

International Nuclear Information System (INIS)

Wang Zhidong; Chen Xiaohua; Dong Bo; Zhang Junquan; Rao Yalan; Gao Ronglian; Hou Lili; Mao Bingzhi

2005-01-01

To explore the early diagnostic factors, new therapeutic targets and mechanisms of acute radiation disease. Proteomic changes of the serum of irradiated mice were studied using 2-DE and Q-TOF-MS approaches. One higher level expressed protein after the irradiation was found, and it was identified as α chain of haptoglobin by Q-TOF-MS. The authors confirmed the result by Western blotting with anti-haptoglobin antibody. Haptoglobin may involve in the process of acute radiation injury. (authors)

Irradiation of protoporphyric mice induces down-regulation of epidermal eicosanoid metabolism

International Nuclear Information System (INIS)

He, D.; Lim, H.W.

1991-01-01

This study investigated the effect of radiation on clinical and histologic changes, and on cutaneous eicosanoid metabolism, in Skh:HR-1 hairless albino mice rendered protoporphyric by the administration of collidine. At 0.1-18 h after exposure to 12 kJ/m2 of 396-406 nm irradiation, thicknesses of back skin and ears were measured, and histologic changes were evaluated by using hematoxylin and eosin (H-E) and Giemsa's stains. Activities of eicosanoid-metabolizing enzymes in epidermal and dermal homogenates were assessed by incubating the tissue homogenates with 3H-AA, followed by quantitation of the eicosanoids generated by radio-TLC. In irradiated protoporphyric mice, an increase of back-skin thickness was noted at 0.1 h, reaching a peak at 18 h, whereas maximal increase in ear thickness was observed at 12 h. Histologic changes included dermal edema, increased mast cell degranulation, and mononuclear cells in the dermis. In these irradiated protoporphyric animals, generations of 6 keto-PGF1a, PGF2a, PGE2, PGD2, and HETE by epidermal eicosanoid-metabolizing enzymes were markedly suppressed at all the timepoints studied. Dermal eicosanoid-metabolizing enzymes of irradiated protoporphyric mice generated increased amounts of PGE2 and HETE at 18 h, probably reflecting the presence of dermal cellular infiltrates. The suppression of the activities of epidermal eicosanoid-metabolizing enzymes was prevented by intraperitoneal injection of WR-2721, a sulfhydryl group generator, prior to irradiation, suggesting that the suppression was secondary to photo-oxidative damage of the enzymes during the in vivo phototoxic response. These results suggest that the effect of protoporphyrin and radiation on cutaneous eicosanoid metabolism in this animal model in vivo is that of a down regulation of the activities of epidermal eicosanoid-metabolizing enzymes

CD44 and Bak expression in IL-6 or TNF-alpha gene knockout mice after whole lung irradiation

International Nuclear Information System (INIS)

Sakai, Minako; Iwakawa, Mayumi; Ohta, Toshie; Tsujii, Hirohiko; Imai, Takashi; Iwakura, Yoichiro

2008-01-01

To understand the molecular mechanisms that underlie radiation pneumonitis, we examined whether knockout of the tumor necrosis factor (TNF) or the interleukin (IL)-6 gene could give mice an inherent resistance to radiation in the acute phase of alveolar damage after thoracic irradiation. The temporal expression of inflammation (CD44) and apoptosis (Bak) markers in lung after thoracic irradiation was measured to determine the degree of alveolar damage. At 4 weeks post-irradiation (10 Gy), small inflammatory foci were observed in all mice, but there were no obvious histological differences between control (C57BL/6JSlc), TNF-alpha knockout (TNF KO), and IL-6 knockout (IL-6 KO) mice. However, immunohistochemical analysis of CD44 and Bak expression over a time course of 2 weeks highlighted significant differences between the three groups. C57BL/6JSlc and TNF KO mice had increased numbers of both CD44-positive and Bak-positive cells after irradiation, while the IL-6 KO mice showed stable levels of CD44 and Bak. In conclusion, the radioresistant status of IL-6 KO mice in the acute phase of alveolar damage after irradiation suggested an important role for IL-6 in radiation pneumonitis. (author)

Interaction of neonatal irradiation and single-genes upon growth and behavior in mice

International Nuclear Information System (INIS)

Nash, D.J.

1977-01-01

Postnatal growth and behavior following neonatal irradiation were studied in congenic strains of mice. Mice were genetically similar except for single-gene substitutions at either the steel or dominant spotting loci. Adult behavior was measured by locomotion and elimination in the open field and by spontaneous activity in exercise wheels. In general, neonatal irradiation caused a decrease in body weight, activity in exercise wheels, and elimination in the open field, but an increase in locomotion in the open field. Significant differences due to genotype and sex were observed for locomotion and body weight. Differential responses of the genotypes to neonatal irradiation were observed in body weight and in activity in exercise wheels. The genotypes, in order of increasing sensitivity, were +/+, Wsup(a)/+, and Slsup(gb)/+. (author)

Brain fibronectin expression in prenatally irradiated mice

International Nuclear Information System (INIS)

Meznarich, H.K.; McCoy, L.S.; Bale, T.L.; Stiegler, G.L.; Sikov, M.R.

1993-01-01

Activation of gene transcription by radiation has been recently demonstrated in vivo. However, little is known on the specificity of these alterations on gene transcription. Prenatal irradiation is a known teratogen that affects the developing mammalian central nervous system (CNS). Altered neuronal migration has been suggested as a mechanism for abnormal development of prenatally irradiated brains. Fibronectin (FN), an extracellular glycoprotein, is essential for neural crest cell migration and neural cell growth. In addition, elevated levels of FN have been found in the extracellular matrix of irradiated lung. To test whether brain FN is affected by radiation, either FN level in insoluble matrix fraction or expression of FN mRNA was examined pre- and postnatally after irradiation. Mice (CD1), at 13 d of gestation (DG), served either as controls or were irradiated with 14 DG, 17 DG, or 5,6, or 14 d postnatal. Brain and liver were collected from offspring and analyzed for either total FN protein levels or relative mRNAs for FN and tubulin. Results of prenatal irradiation on reduction of postnatal brain weight relative to whole are comparable to that reported by others. Insoluble matrix fraction (IMF) per gram of brain, liver, lung, and heart weight was not significantly different either between control and irradiated groups or between postnatal stages, suggesting that radiation did not affect the IMF. However, total amounts of FN in brain IMF at 17 DG were significantly different (p < .02) between normal (1.66 ± 0.80 μg) and irradiated brains (0.58 ± 0.22 μg). FN mRNA was detectable at 13, 14, and 17 DG, but was not detectable at 6 and 14 d postnatal, indicating that FN mRNA is developmentally regulated. 41 refs., 4 figs., 3 tabs

The activity of dehydrogenases in the uterus of C57B mice after X-irradiation and serotonin treatment

International Nuclear Information System (INIS)

Mazur, L.

1978-01-01

In C57B female mice, irradiated with 500 R and/or treated with serotonin (5-hydroxytryptamine), the activity of dehydrogenases in the uterus was studied on the fourth day of pregnancy. The reduction of 2,3,5-triphenyltetrazolium chloride to formazane by the uterine tissue was taken as the measure of such activity. The activity of dehydrogenases in the uterus of irradiated mice was distinctly lower than in non-irradiated controls. This activity was also depressed after serotonin treatment, the level of enzyme activity being dose-dependent. In females injected with serotonin and then irradiated, the activity of dehydrogenases was higher than in those irradiated only. The radioprotective effect was more pronounced in mice injected with serotonin alone on the third day of pregnancy i.e. shortly before irradiation, than in those injected on the second and the third day. (author)

Induction of external abnormalities in offspring of male mice irradiated with 252Cf neutron

International Nuclear Information System (INIS)

Kurishita, Akihiro; Ono, Tetsuya; Mori, Yuriko; Okada, Shigefumi; Sawada, Syozo

1992-01-01

To assess the genetic effects of fission neutron, the induction of external malformations was studied in F 1 fetuses after F 0 male mice were irradiated. Male mice of the ICR:MCH strain were irradiated with 252 Cf neutron at doses of 0.238, 0.475, 0.95 and 1.9 Gy. They were mated with non-irradiated female mice at 71-120 days after irradiation. Pregnant females were autopsied on day 18 of gestation and their fetuses were examined for deaths and external abnormalities. No increases of pre- and post-implantation losses were noted at any dose. External abnormalities were observed at rates of 1.40% in the 0.238 Gy, 2.23% in the 0.475 Gy, 3.36% in the 0.95 and 3.26% in the 1.9 Gy groups; the rate in the control group was 1.65%. The dose-response curve was linear up to 0.95 Gy, and then flattened out; the induction rate of external abnormalities was 2.7x10 -4 /gamete/cGy based on the linear regression. These results indicated that fission neutron effectively induces external abnormalities in F 1 fetuses after spermatogonial irradiation. (author). 29 refs.; 1 fig.; 2 tabs

Berberine inhibits the chemotherapy-induced repopulation by suppressing the arachidonic acid metabolic pathway and phosphorylation of FAK in ovarian cancer.

Science.gov (United States)

Zhao, Yawei; Cui, Lianzhi; Pan, Yue; Shao, Dan; Zheng, Xiao; Zhang, Fan; Zhang, Hansi; He, Kan; Chen, Li

2017-12-01

Cytotoxic chemotherapy is an effective and traditional treatment of ovarian cancer. However, chemotherapy-induced apoptosis may also trigger and ultimately accelerate the repopulation of the small number of adjacent surviving cells. This study mainly focused on the tumour cell repopulation caused by chemotherapy in ovarian cancer and the adjunctive/synergistic effect of Berberine on the prevention of tumour repopulation. The transwell system was used to mimic the co-culture of surviving ovarian cancer cells in the microenvironment of cytotoxic chemotherapy-treated dying cells. Tumour cell proliferation was observed by crystal violet staining. AA and PGE 2 levels were measured by ELISA, and changes of protein expression were analysed by Western blot. Chemotherapy drug VP16 treatment triggered AA pathway, leading to the elevated PGE 2 level, and ultimately enhanced the repopulation of ovarian cancer cells. Berberine can block the caspase 3-iPLA 2 -AA-COX-2-PGE 2 pathway by inhibiting the expression of iPLA 2 and COX-2. Berberine can also reverse the increased phosphorylation of FAK caused by abnormal PGE 2 level and thus reverse the repopulation of ovarian cancer cells after VP16 treatment. Our observation suggested that Berberine could inhibit the chemotherapy-induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation. © 2017 John Wiley & Sons Ltd.

Amelioration of radiation damage to haemopoiesis by Ivastimul, given after irradiation to mice protected by peroral cystamine

International Nuclear Information System (INIS)

Vacek, A.; Rotkovska, D.; Bartonickova, A.; Kautska, J.

1992-01-01

Combined radioprotection by preirradiation peroral cystamine and postirradiation Ivastimul administration was examined in sublethally and lethally whole-body gamma-irradiated mice. Enhancement of haemopoietic recovery and increased survival of irradiated mice was demonstrated for a single dose of Ivastimul administered after irradiation. The ameliorative influence of combined radioprotection may be explained by haemopoietic stem cell protection by cystamine and haemopoietic stimulation mediated by Ivastimul. (author) 2 tabs., 3 figs., 20 refs

Importance of tumor size and repopulation for radiocurability of skin cancer

International Nuclear Information System (INIS)

Maciejewski, B.A.; Zajusz, A.; Lange, D.

1993-01-01

Data on 946 skin cancers treated by radiation were used to estimate the importance of repopulation. Six different treatment regimes were used, from a single dose to 74 Gy given in 47 fractions. High local control of the small skin cancers (L 1 cm) was independent of dose fractionation. For large tumors, only 74 Gy in 47 fractions was the optimal treatment. Time factor analysis showed a steep increase in the NTD50 values between day 28 and 65 of treatment. This implies that tumor clonogen repopulation starts around 4 weeks of treatment. The present results show a three-component dose-response curve instead of the two-component curves which were found for head and neck and bladder cancer. (author) 1 tab., 2 figs., 15 refs

Biochemical aspects of the immunomodular action in irradiated survival mice with 60C gama irradiation

International Nuclear Information System (INIS)

Garcia Agudo, N.L. del M. de.

1983-01-01

The radioprotective action of Calmetti-Guerin bacillus (BCG), Corynebacterium parvum, Escherichia coli Lipopolysccharides (LPS) and peptone proteose was evaluated. A single injection of the macrophage activiting agents prior to 60 Co whole-body irradiation increased the survival rate of mice in the lethal dose range. (L.M.J.) [pt

Acute myeloid leukemia induction in CBA/H mice by irradiation with fission neutrons as a function of exposure rate

International Nuclear Information System (INIS)

Huiskamp, R.

1991-01-01

Radiation-induced acute myeloid leukemia (AML) in male CBA/H mice was used as a model for investigation of the effect of reduced fast fission neutron exposure rates on radiation-induced carcinogenesis. Groups of about 90 male CBA/H mice were irradiated or sham-irradiated at the age of 15-20 weeks. The animals were exposed to 400 mGy fast fission neutrons at exposure rates of 2, 10 or 100 mGy/min. The investigation clearly showed that reducing the exposure rate of high-LET fast fission neutrons had no influence on the incidence of AML or on the survival of the irradiated mice. In contrast, a higher incidence of lymphosarcomas was observed in mice irradiated with higher exposure rates. (orig./MG)

Acute myeloid leukemia induction in CBA/H mice by irradiation with fission neutrons as a function of exposure rate

Energy Technology Data Exchange (ETDEWEB)

Huiskamp, R [Stichting Energieonderzoek Centrum Nederland, Petten (Netherlands). Radiobiology and Radio-Ecology Unit

1991-06-01

Radiation-induced acute myeloid leukemia (AML) in male CBA/H mice was used as a model for investigation of the effect of reduced fast fission neutron exposure rates on radiation-induced carcinogenesis. Groups of about 90 male CBA/H mice were irradiated or sham-irradiated at the age of 15-20 weeks. The animals were exposed to 400 mGy fast fission neutrons at exposure rates of 2, 10 or 100 mGy/min. The investigation clearly showed that reducing the exposure rate of high-LET fast fission neutrons had no influence on the incidence of AML or on the survival of the irradiated mice. In contrast, a higher incidence of lymphosarcomas was observed in mice irradiated with higher exposure rates. (orig./MG).

Mammary tumorigenesis in APCmin/+ mice is enhanced by X-irradiation with a characteristic age dependence

International Nuclear Information System (INIS)

Tatsuhiko, Imaoka; Mayumi, Nishimura; Shizuko, Kakinuma; Yoshiya, Shimada; Mieko, Okamoto

2006-01-01

The ApcM min/+ (Min) mouse is a genetically predisposed model of both intestinal and mammary tumorigenesis. We investigated age-related changes in the susceptibility of mice (before, during and after puberty) to radiation-induced mammary tumorigenesis using this model. Female Min and wild-type mice having the C57BL/6J background were irradiated with 2 Gy of X-rays at 2, 5, 7 and 10 weeks and sacrificed at 18 weeks of age. Min mice irradiated at 7 to 10 weeks of age (after puberty) developed mammary tumors with squamous metaplasia, whereas their wild-type litter-mates did not. Interestingly, irradiation of Min mice at 2 to 5 weeks (before and during puberty, respectively) did not induce mammary tumors but rather cystic nodules with metaplasia. The mammary tumors exhibited increased nuclear beta-catenin protein and loss of the wild-type Apc allele. Our results show that susceptibility to radiation-induced mammary tumorigenesis increases after puberty in Min mice, suggesting that the tumorigenic effect of ionizing radiation targets the lobular-alveolar progenitor cells, which increase in number with age and are controlled by beta-catenin signaling. (author)

Studies at Dounreay on the repopulation of offshore sediments by hot particles

International Nuclear Information System (INIS)

Crawford, Ron; Toole, Joe; Innes, Steve

2007-01-01

Since 2000, much of the effort of diving surveys offshore of Dounreay to locate the presence of radioactive particles in the seabed sediments has been directed to a programme of repopulation studies, in which selected areas of the seabed have been surveyed a number of times and cleared of identified particles on each occasion. This work has led to an understanding of the distribution of particles within the seabed off Dounreay. The two-population model originally proposed by Atkinson (2001 UKAEA Document reference 000052) and further refined into three populations by Clayton and Atkinson (2002 UKAEA Document PSG Issue Note (02)33) has been substantially confirmed by the extended data set now available. It is apparent that the upper layers of the seabed sediments, containing a population of particles, are essentially mobile. These sediments migrate over the seabed driven by tidal wave and surge induced seabed currents, recontaminating areas which have been previously cleared of particles. The number of particles present in this layer at any given location has not been effectively reduced by the removal of particles over the years, nor has the distribution of activity within this population varied significantly. The highest concentration of particles, and the most active, reside close to and to the northeast of the effluent diffuser outfall. Particle numbers and their activity decrease with distance from the diffuser, and the rate of decrease is significantly greater to the southwest compared to the northeast. By contrast, there is evidence that the population of particles retained in the deeper sediments has changed significantly as a result of the repopulation surveys. Close to the diffuser, the population of particles identified at depth during initial surveys is high and contains significantly more highly active particles than are found in the surface sediments. It is also evident that once the deeper sediments are cleared of particles, the level of repopulation

Effect of tocopherol-monoglucoside (TMG), a water-soluble glycosylated derivate of vitamin E, on hematopoietic recovery in irradiated mice.

Science.gov (United States)

Cherdyntseva, Nadezda; Shishkina, Anna; Butorin, Ivan; Murase, Hironobu; Gervas, Polina; Kagiya, Tsutomu V

2005-03-01

A preparation of alpha-tocopherol monoglucoside (TMG) administered i.p. at a dose of 600 mg/kg immediately after whole body gamma irradiation was examined for its radioprotective efficacy towards bone marrow and peripheral blood nucleated cells. When mice received X-rays at a dose of 5,6 Gy, a marked decrease in bone marrow karyocytes and a reduction of peripheral leukocytes within the early post-irradiated period were observed. However these changes were attenuated in TMG-treated mice. Significant protection of blood lymphocytes was found for the TMG group of mice. The return to normal value of the reduced blood leukocyte count starting from the 8th day was more rapid in TMG-treated mice than in untreated irradiated mice. TMG administration was found to enhance hematopoietic recovery, as measured by the exceeded nucleated bone marrow cell count due to elevated amount of both lymphoid and granulocytic elements in the TMG-group, in comparison with that of both control irradiated and non-irradiated animals. These findings indicate that the radioprotective effect of TMG is apparently realized through its influence on hematopoietic system.

[Effect of electromagnetic pulse irradiation on structure and function of Leydig cells in mice].

Science.gov (United States)

Wang, Shui-Ming; Wang, De-Wen; Peng, Rui-Yun; Gao, Ya-Bing; Yang, Yi; Hu, Wen-Hua; Chen, Hao-Yu; Zhang, You-Ren; Gao, Yan

2003-08-01

To explore the effect of electromagnetic pulse (EMP) irradiation on structure and function of Leydig cells in mice. One hundred and fourteen male Kunming mice were randomly divided into irradiated and control group, the former radiated generally by 8 x 10(3) V/m, 2 x 10(4) V/m and 6 x 10(4) V/m EMP respectively five times within two minutes. Pathological changes of Leydig cells were observed by light and electron microscope. Serum testosterone (T), luteinizing hormone (LH) and estradiol (E2) were measured dynamically by radioimmunoassay at 6 h, 1 d, 3 d, 7 d, 14 d and 28 d after irradiation. Main pathological changes were edema and vacuolation, swelling of cytoplasmic mitochondria, reduce of lipid droplets, pale staining of most of lipid droplets, and partial or complete cavitation of lipid droplets in Leydig cells within 28 days after EMP radiation. Compared with normal controls, serum T decreased in all in different degrees within 28 days, and dropped significantly at 6 h-14 d, 6 h-7 d and 1 d-28 d after 8 x 10(3) V/m, 2 x 10(4) V/m and 6 x 10(4) V/m EMP irradiation(P < 0.05 or P < 0.01). EMP irradiation caused no significant changes in serum LH and E2. Leydig cells are among those that are the most susceptible to EMP irradiation. EMP irradiation may cause significant injury in structure and function of Leydig cells in mice, whose earlier and continuous effect is bound to affect sexual function and sperm production.

Entire litters developed from transferred eggs in whole body x-irradiated female mice

International Nuclear Information System (INIS)

Lin, T.P.

1980-01-01

The sensitivity of mouse eggs to sublethal x-irradiation was determined in vitro and in vivo with regard to the development of donor litters in foster mothers. One thousand seven hundred fifty-eight unfertilized eggs of agouti dark-eyed donor mice were transferred into 293 unirradiated or x-irradiated, mated female pink-eyed mice. Two hundred thirty-nine recipients became pregnant; of these 35 produced litters containing solely dark-eyed fetuses. Sublethal doses of x-radiation administered to donor eggs in vitro before transferring into unirradiated recipients did not influence significantly the number of litters of exclusively dark-eyed fetuses produced. However, recipients irradiated by 250 roentgens (r) produced more solely dark-eyed litters than did those irradiated with 100 r. In 21 pregnant females irradiated by 100 r, only 3 (14%) developed solely dark-eyed fetuses as compared to 22 pregnant females irradiated by 250 r, of which 13 (59%) developed solely dark-eyed fetuses, all from unirradiated, transferred eggs. Of another group of 22 pregnant females which received 250 r body irradiation and subsequently received eggs also irradiated by 250 r, only 7 (32%) produced litters of dark-eyed fetuses. No one female of these three groups carried native fetuses. Such radiation-induced infertility resulting from damage of native eggs rather than loss of mother's ability to carry a pregnancy, is frequently remedied by egg transfer

Absorbed dose to mice in prolonged irradiation by low-dose rate ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Shiragai, Akihiro [National Inst. of Radiological Sciences, Chiba (Japan); Saitou, Mikio; Kudo, Iwao [and others

2000-07-01

In this paper, the dose absorbed by mice was evaluated as a preliminary study of the late effects of prolonged continuous irradiation of mice with low-dose rate ionizing radiation. Eight-week-old male and female SPF C3H/HeN mice in three irradiation rooms were exposed to irradiation at 8000, 400, and 20 mGy, respectively, using a {sup 137}Cs {gamma}-source. Nine racks were arranged in a circle approximately 2.5 m from the source in each room, and 10 cages were arranged on the 4 shelves of each rack. Dose distributions, such as in air at the source level, in the three rooms were estimated by using ionization chambers, and the absorbed dose distributions in the room and relative dose distributions in the cages in relation to the distance of the cage center were examined. The mean abdomen doses of the mice measured by TLD were compared with the absorbed doses in the cages. The absorbed dose distributions showed not only inverse-inverse-square-law behavior with distance from the source, but geometric symmetry in every room. The inherent scattering and absorption in each room are responsible for such behavior and asymmetry. Comparison of relative dose distributions revealed cage positions that are not suitable for experiments with high precision doses, but all positions can be used for prolonged continuous irradiation experiments if the position of the cages is rotated regularly. The mean abdomen doses of the mice were similar in each cage. The mean abdomen doses of the mice and the absorbed doses in a cage were almost the same in all cages. Except for errors concerning the positions of the racks and cages, the uncertainties in the exposure doses were estimated to be about {+-}12% for 8000 mGy group, 17% for 400 mGy group, and 35% for 20 mGy group. (K.H.)

L-carnitine protects against testicular dysfunction caused by gamma irradiation in mice.

Science.gov (United States)

Ahmed, Mohamed Mohamed; Ibrahim, Zein Shaban; Alkafafy, Mohamed; El-Shazly, Samir Ahmed

2014-07-01

This study was conducted on mice to evaluate the radioprotective role of L-carnitine against γ-ray irradiation-induced testicular damage. Adult male mice were exposed to whole body irradiation at a total dose of 1 Gy. Radiation exposure was continued 24 h a day (0.1 Gy/day) throughout the 10 days exposure period either in the absence and/or presence of L-carnitine at an i.p. dose of 10 mg/kg body weight/day. Results revealed that γ-rays irradiation suppressed the expression of ABP and CYP450SCC mRNA, whereas treatment with L-carnitine prior and throughout γ-rays irradiation exposure inhibited this suppression. Treatment with γ-ray irradiation or L-carnitine down-regulated expression of aromatase mRNA. With combined treatment, L-carnitine significantly normalized aromatase expression. γ-Ray irradiation up-regulated expression of FasL and Cyclin D2 mRNA, while L-carnitine inhibited these up-regulations. Results also showed that γ-ray-irradiation up-regulated TNF-α, IL1-β and IFN-γ mRNA expressions compared to either controls or the L-carnitine treated group. Moreover, γ-irradiation greatly reduced serum testosterone levels, while L-carnitine, either alone or in combination with irradiation, significantly increased serum testosterone levels compared to controls. In addition, γ-irradiation induced high levels of sperm abnormalities (43%) which were decreased to 12% in the presence of L-carnitine. In parallel with these findings, histological examination showed that γ-irradiation induced severe tubular degenerative changes, which were reduced by L-carnitine pre-treatment. These results clarified the immunostimulatory effects of L-carnitine and its radioprotective role against testicular injury. Copyright © 2014 Elsevier GmbH. All rights reserved.

Anti-tumor effect of total body irradiation of low doses on WHT/Ht mice

International Nuclear Information System (INIS)

Miyamoto, Miyako; Sakamoto, Kiyohiko

1987-01-01

The effect of low dose (0.05 - 1.0 Gy) of total body irradiation (TBI) on non-tumor bearing and tumor bearing mice were investigated. Mice received TBI of 0.1 Gy during 6 - 12 hours before tumor cell inoculation demonstrated to need larger number of tumor cells (approximately 2.5 times) for 50 per cent tumor incidence, compared to recipient mice not to receive TBI. On the other hand, in tumor bearing mice given 0.1 Gy of TBI only tumor cell killing effect was not detected, however enhancement of tumor cell killing effect and prolonged growth delay were observed when tumor bearing mice were treated with 0.1 Gy of TBI in combined with local irradiation on tumors, especially cell killing effect was remarkable in dose range over 6 Gy of local exposure. The mechanism of the effect of 0.1 Gy TBI is considered to be host mediated reactions from the other our experimental results. (author)

The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice

Energy Technology Data Exchange (ETDEWEB)

Allam, Ayman; Perez, Luis A; Huang, Peigen; Taghian, Alphonse; Azinovic, Ignacio; Freeman, Jill; Duffy, Michael; Efird, Jimmy; Suit, Herman D

1995-04-30

Purpose: To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (T{sub pot}) of this tumor to the effective doubling time (T{sub eff}) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. Methods and Materials: The TCP was assessed using the TCD{sub 50} value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7-8 mm. The mean interfraction intervals were from 8-24 h. The T{sub pot} was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to T{sub eff}. Results: The TCD{sub 50} values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD{sub 50} values was significant (p < 0.05) between groups 1 and 2 (30 fractions/10 days and 30 fractions/15 days) vs. group 3 (30 fractions/30 days). The loss in TCP due to the prolongation of the overall treatment time from 10 days to 30 days was found to be 1.35-1.4 Gy/day. The pretreatment T{sub pot} (2.4 days) was longer than the calculated T{sub eff} in groups 2 and 3 (1.35 days). Conclusion: Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an

Transcriptome profiling of mice testes following low dose irradiation

DEFF Research Database (Denmark)

Belling, Kirstine C.; Tanaka, Masami; Dalgaard, Marlene Danner

2013-01-01

ABSTRACT: BACKGROUND: Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types...... in the adult testis. METHODS: Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were...... selected for further analysis. These transcripts were separated into clusters and their cellular origin was determined. Immunohistochemistry and in silico quantification was further used to study cellular changes post-irradiation (pi). RESULTS: We identified a subset of transcripts (n = 988) where changes...

Adaptive response of spermatogenic cell apoptosis selectively induced by low dose X-ray irradiation in mice

International Nuclear Information System (INIS)

Liu Guangwei; Dong Lihua; Liu Yang; Lv Zhe; Liu Shuchun; Gong Shouliang

2003-01-01

Objective: The adaptive response of spermatogenic cell apoptosis induced by whole-body X-ray irradiation at low doses was studied in mice. Methods: Kunming male mice were irradiated with an inductive dose (D1:75 mGy) and/or a challenging dose (D2:1.0, 2.0 or 3.0 Gy). Different kinds of spermatogenic cells were separated using density gradient centrifugation and their apoptotic percentages were analysed using flow cytometry (FCM). Results: When the mice were irradiated with D1 6 h before irradiation with D2, the apoptotic percentages of the spermatogonia and spermatocytes declined rapidly as compared with those in the groups irradiated with D2 only, and those of spermatids and spermatozoa showed no significant changes. When the interval times between D1 and D2 was 3, 6, 12 or 24 h, the apoptotic percentages in spermatogonia and spermatocytes reduced early, significantly and continued for a longer duration after smaller D2(1.0 and 2.0 Gy) irradiation, while the apoptotic percentages did not change after larger D2(3.0 Gy) irradiation. Conclusion: The adaptive response of apoptosis in spermatogonia and spermatocytes could be selectively induced by low dose X-ray irradiation. The adaptive response could be closely related to the D2 dose and interval time between D1 and D2

Life-shortening and carcinogenesis in mice irradiated neonatally with x rays

International Nuclear Information System (INIS)

Sasaki, S.; Kasuga, T.

1981-01-01

The characteristics of life-shortening and carcinogenesis were investigated in x-irradiated neonatal B6WFr mice. Animals were irradiated with 24 hr after birth and allowed to complete their normal life span. Mean life span was shortened linearly with doses at a rate of 9.1% per 100 R for females and 9.8% for males. The spectrum of neoplastic diseases was apparently modulated by x irradiation, showing neonatal B6WFr mice to be highly susceptible to the induction of thymic lymphoma, liver tumor, and pituitary tumor. The dose-response relationship for thymice lymphoma could be described by a linear-quadratic model, and linearity could be rejected. Thymic lymphoma developed after a short latent period, resulting in death between 100 and 450 days of age. Liver and pituitary tumors increased with increasing dose up to 400 R and decreased thereafter. The latent period for liver tumor development was apparently shortened with increasing doses. Pituitary tumor developed in excess only in females after a long latent period

Schistosoma mansoni: vaccination of mice with 10-krad-irradiated, cryopreserved schistosomules

International Nuclear Information System (INIS)

Lewis, F.A.; Stirewalt, M.A.; Leef, J.L.

1984-01-01

Protection against a Schistosoma mansoni cercarial challenge was evaluated in mice immunized with a vaccine composed of 10-krad-irradiated, cryopreserved schistosomules. The level of resistance induced in C57B1/6 or NMRI (CV) mice increased with the number of schistosomules injected. Up to 83% reduction in challenge worm burden was achieved when 5000 schistosomules were injected per mouse. Intramuscular injection of the vaccine was superior to subcutaneous. Multiple immunizations, up to 3 at 4-week intervals, did not increase the resistance induced by a single immunization. A high level of protection developed in as little as 2 weeks and was maintained through at least 12 weeks postimmunization. The vaccine irradiated with 10 krad from either a 60-cobalt or 137-cesium source induced equivalent levels of resistance, and no differences were found in the immunogenicity of vaccines comprised of organisms irradiated as cercariae or as 1- to 3-hr-old schistosomules. These findings are basic to the development of a cryopreserved, live vaccine against schistosomiasis of humans or domestic animals

Molecular characterization of non-thymic lymphomas in mice exposed to continuous low-dose-rate g-ray irradiation

International Nuclear Information System (INIS)

Takabatake, T.; Fujikawa, K.; Nakamura, S.; Tanaka, S.; Tanaka, I.; Tanaka-Braga III, I.; Sunaga, Y.; Ichinoche, K.; Sato, F.; Tanaka, K.; Matsumoto, T.

2004-01-01

To investigate the effects of continuous low-dose-rate irradiation on life span and neoplasm incidence, SPE B6C3 F1 mice were irradiated with 137Cs-ray at dose-rates of 20, 1 and 0.05 mGy/day with accumulated doses equivalent to 8000, 40 and 20 mGy, respectively. Examination of a total of 3,000 irradiated and 1,000 non-irradiated control mice showed that the life spans of the both sexes irradiated at 20 mGy/day, respectively. Examination of a total of 3,000 irradiated and 1,000 non-irradiated control mice showed that the life spans of the both sexes irradiated at 20 mGy/day were significantly shorter than that of the non-irradiated group. No significant difference in the cause of death and mortality rates was found between the groups. However, non-thymic lymphomas, the most common lethal neoplasm, showed a tendency to develop at an earlier age in mice irradiated with 20 mGy/day, regardless of sex. to obtain clues on the molecular mechanisms underlying the earlier development of non-thymic lymphomas in 20 mGy/day irradiated group, detailed molecular characterizations of non-thymic lymphomas with respect to B-cell or T-cell origin was done by detecting rearrangements in immunoglobulin heavy gene and in T-cell receptor b-and g chain genes by Southem hybridization method. to determine whether the early development of non-thymic lymphomas in 20 mGy/day irradiated group is associated wi the any recurrent chromosomal imbalance such as deletions and amplifications, the genome-wide scanning is also currently in progress by both LOH and array CGH methods. Present data obtained by LOH method show that deletions in parts of chromosomes 11 and 12 were more frequent than in chromosomes 2, 4 and 14 in both the non-irradiated control and 20 mGy/day irradiated groups. this work is supported by grants from Aomori Prefecture, Japan. (Author)

Caffeine protects mice against whole-body lethal dose of {gamma}-irradiation

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George, K.C.; Hebbar, S.A.; Kale, S.P.; Kesavan, P.C. [Biosciences Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

1999-06-01

Administration of caffeine (1,3,7-trimethylxanthine), a major component of coffee, to Swiss mice at doses of 80 or 100 mg/kg body weight 60 min prior to whole-body lethal dose of {gamma}-irradiation (7.5 Gy) resulted in the survival of 70 and 63% of animals, respectively, at the above doses in contrast to absolutely no survivors (LD-100/25 days) in the group exposed to radiation alone. Pre-treatment with a lower concentration of caffeine (50 mg/kg) did not confer any radioprotection. The protection exerted by caffeine (80 mg/kg), however, was reduced from 70 to 50% if administered 30 min prior to irradiation. The trend statistics reveal that a dose of 80 mg/kg administered 60 min before whole-body exposure to 7.5 Gy is optimal for maximal radioprotection. However, caffeine (80 mg/kg) administered within 3 min after irradiation offered no protection. While there is documentation in the literature that caffeine is an antioxidant and radioprotector against the toxic pathway of radiation damage in a wide range of cells and organisms, this is the first report demonstrating unequivocally its potent radioprotective action in terms of survival of lethally whole-body irradiated mice. (author)

Micronucleus test in mice fed on irradiated whole diet

International Nuclear Information System (INIS)

Reddy, P.P.; Reddi, O.S.; Pentiah, P.R.; Rani, M.V.U.; Devi, K.R.; Goud, S.N.

1981-01-01

Eight week old Swiss albino male mice were fed on freshly irradiated or unirradiated whole diet for one week. (Exposure was to 75 or 200 kR γ rays from a 1000 Ci 60 Co γ source at a dose rate of 584 R/min.) On the seventh day, six hours after feeding, the mice were killed and bone marrow preparations were made by the Schmid technique. From each group three animals were taken and from each animal 2000 polychromatic and normochromatic erythrocytes were scored. It was evident from the data obtained that the irradiated whole diet failed to induce any significant increase in the incidence of micronuclei in polychromatic erythrocytes. Similarly, there was no significant increase in the frequency of micronuclei in normochromatic erythrocytes when compared with control data. The polychromatic to normochromatic ratio was also unaffected. The diet consisted of wheat flour (60%). groundnut cake (20%), fish meal (8%), Bengal gram flour (8%), dried yeast (3%), salt/mineral mixture (1%) and traces of vitamins. (U.K.)

Stimulation of anti-tumor effect by low-dose irradiation. Pt. 2. The prolongation of life span in AKR mice

International Nuclear Information System (INIS)

Ishii, Keiichiro; Misonoh, Jun; Hosoi, Yoshio; Ono, Tetsuya; Sakamoto, Kiyohiko.

1994-01-01

To elucidate the antileukemic effect of low-dose X-irradiation, we studied the influence of periodical low-dose X-irradiation on survival and tumor incidence of thymus using AKR mice. The findings of the experiments were as follows; (1) The median survival time of control AKR mice was 283±3 days. It of irradiation group of 15 cGy/week and 30cGy was 309±14 days and 316±10 days respectively. The life span was significantly prolonged (p < 0.05 and p < 0.01 respectively by Wilcoxon test) by periodical low-dose X-irradiation in term of breeding. (2) The incidence of thymus tumor which is observed remarkably in control AKR mice was 48.8%. It of irradiation group of 15 cGy/week and 30 cGy/week was 40% and 20% respectively. Inversely, the non-tumor incidence of tymus in control AKR mice was 19.5%. It of irradiation group of 15 cGy/week and 30 cGy/week was 32.5% and 51.4% respectively. The thymic tumor incidence was significantly decreased (p < 0.01 by chi-square test) in irradiation group of 30 cGy/week. (3) The incidence of thymic lymphoma as a death cause in control AKR mice was 80.4%. It of irradiation group of 15 cGy/week and 30cGy/week was 67.5% and 48.6% respectively. The incidence of thymic lymphoma was significantly decreased (p < 0.05 by chi-square test) in irradiation group of 30 cGy/week. (author)

Influence of conditioned psychological stress on immunological recovery in mice exposed to low-dose x irradiation

International Nuclear Information System (INIS)

Sato, K.; Flood, J.F.; Makinodan, T.

1984-01-01

A study was initiated to determine the effects of psychological stress on the immune response in BALB/c mice recovering from exposure to a low dose of ionizing radiation. Mice were first subjected to conditioning training for 12 days, then exposed to 200 R, subjected to psychological stress for 14 days, and assessed for peak anti-sheep RBC response. The seven treatment groups included two unirradiated groups and five irradiated groups. Mice exposed to 200 R and then subjected to conditioned psychological stress responded less vigorously to antigenic stimulation than those of the other irradiated groups. The psychological stress imposed upon these mice did not influence the antibody-forming capacity of unirradiated mice. These results indicate that a psychological stress which did not affect the immunological activity of unirradiated mice can curtail the immunological recovery of mice exposed to low doses of ionizing radiation

Resistance to mycobacteria in mice treated with fractionated total lymphoid irradiation (TLI) and in mice reconstituted with allogeneic bone marrow cells following radiotherapy

International Nuclear Information System (INIS)

Mor, N.; Lutsky, I.; Weiss, L.; Morecki, S.; Slavin, S.

1985-01-01

The increased clinical use of total lymphoid irradiation (TLI) as an immunosuppressive adjunct in transplantation suggested the need for determining the effects of TLI on the in vivo susceptibility of animals to infections controlled by cell-mediated immunity. TLI-treated, TLI-treated and splenectomized, and chimeric mice prepared with TLI were inoculated in the hind foot pad with Mycobacterium marinum or Mycobacterium leprae. Although M. marinum organisms multiplied in greater numbers in the TLI mice, ultimately they were destroyed as effectively in TLI mice as in the non-irradiated control mice. M. leprae multiplied at the same rate and to the same maximum in TLI mice as in controls. Mice previously challenged with M. marinum in one hind foot pad, and challenged subsequently with the same organism in the opposite hind foot pad, showed a solid immunity against this reinfection. It appears that upon recovery from the immediate effects of radiotherapy TLI-treated mice are able to mount an effective immune response to experimental infection with M. marinum and M. leprae

Resistance to mycobacteria in mice treated with fractionated total lymphoid irradiation (TLI) and in mice reconstituted with allogeneic bone marrow cells following radiotherapy

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Mor, N.; Lutsky, I.; Weiss, L.; Morecki, S.; Slavin, S.

1985-01-01

The increased clinical use of total lymphoid irradiation (TLI) as an immunosuppressive adjunct in transplantation suggested the need for determining the effects of TLI on the in vivo susceptibility of animals to infections controlled by cell-mediated immunity. TLI-treated, TLI-treated and splenectomized, and chimeric mice prepared with TLI were inoculated in the hind foot pad with Mycobacterium marinum or Mycobacterium leprae. Although M. marinum organisms multiplied in greater numbers in the TLI mice, ultimately they were destroyed as effectively in TLI mice as in the non-irradiated control mice. M. leprae multiplied at the same rate and to the same maximum in TLI mice as in controls. Mice previously challenged with M. marinum in one hind foot pad, and challenged subsequently with the same organism in the opposite hind foot pad, showed a solid immunity against this reinfection. It appears that upon recovery from the immediate effects of radiotherapy TLI-treated mice are able to mount an effective immune response to experimental infection with M. marinum and M. leprae.

Unscheduled DNA synthesis in spleen cells of mice exposed to low doses of total body irradiation

International Nuclear Information System (INIS)

Tuschl, H.; Kovac, R.; Hruby, E.

1983-07-01

Unscheduled DNA synthesis was induced by UV irradiation of spleen cells obtained from C 57 Bl mice after repeated total body irradiation of 0.05 Gy 60 Co (0.00125 Gy/mice) and determined autoradiographically. An enhancement in the ability for repair of UV induced DNA lesions was observed in cells of gamma irradiated animals. While the amount of 3 H-thymidine incorporated per cell was increased, the percentage of labeled cells remained unchanged. The present results are compared with previous data on low dose radiation exposure in men. (Author) [de

Hematopoietic effects of early and long terms of rhG-CSF in mice exposed to 6.5 Gy irradiation

International Nuclear Information System (INIS)

Cong Yuwen; Mao Bingzhi; Luo Qingliang; Dong Bo; Chen Huipeng

1996-01-01

In order to evaluate the long-term protective effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on hematopoiesis after a second irradiation, different doses of rhG-CSF were given to 6.5 Gy 60 Co γ-ray irradiated C 57 BL/6 mice. When the peripheral blood cells recovered to normal level, the survived mice were exposed to a second dose of radiation exactly the same as the first one. It was showed that peripheral WBC, RBC and platelet counts recovered much quicker in the mice treated with the factor after irradiation and the effect was dependent on the dose of rhG-CSF. In the survived mice exposed to a second dose of γ-rays 45 days after the first irradiation, as compared with the control, the recovery of peripheral blood cell counts was evidently accelerated and the survival rate was markedly elevated. These results not only demonstrate that the recovery of hematopoiesis in the irradiated mice could be accelerated after the administration of rhG-CSF but also suggest that early administration of the factor could produce a long-term protective effect on the hematopoietic function against a second irradiation given 45 days later

Polyherbal EMSA ERITIN Promotes Erythroid Lineages and Lymphocyte Migration in Irradiated Mice

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Ibrahim Mansur

2016-01-01

Full Text Available Radiotherapy is commonly used to kill malignant cells, but it can significantly deplete hematopoietic and splenic erythroblasts. Radioprotective agents are therefore very important in clinical radiotherapy. We examined the effect of poly-herbal EMSA ERITIN on immunological responses when administered to sublethally irradiated mice with the aim of highlighting promotes erythroid lineages and lymphocytes migration in irradiated mice with the parameter are TER119+CD123+in bone marrow and SDF-1 in bone marrow and spleen organ. Normal BALB/c mice were sublethally irradiated with 600 rad. EMSA ERITIN was administered orally at different doses:(1.04, 3.125 and 9.375 mg/g body weight for 15 days. On day 16 erythroid lineages (TER-119+CD123+ were observed in bone marrow and lymphocytes migration by the production of SDF-1 in spleen and bone marrow. Lymphocytes migration was indicated by the production of SDF-1 in spleen and bone marrow using flow cytometry analysis. EMSA ERITIN increased the generation of erythroid lineage cells marked by TER119+CD123+ and promoted lymphocyte migration by increasing SDF-1 production in bone marrow and spleen. EMSA ERITIN appears to be a powerful medicinal herb with potential as a food supplement to normalize homeostasis and erythropoiesis after radiation.

Types of repair in radiosensitive organs of mice subjected to continuous γ-irradiation

International Nuclear Information System (INIS)

Li Yuanmin; Hu Fenghua; Gao Yabin

1990-01-01

LACA mice were whole-body irradiated with 1 Gy continuous γ-irradiation for 22 hours daily. Animals were divided into groups according to different cumulative doses of 10, 15, 20, 25 and 30 Gy, and were sacrificed at different intervals after the termination of irradiation when the above doses were reached. Radiosensitive organs were stduied by determination of quantitative indices and microscopic examination of histopathological sections. Three types of repair of radiation damages were found in radiosensitive organs, i.e. (1) full repair during irradiation in small intestines, (2) repair only after cessation of irradiation in hemopoietic and lymphoid tissues, and (3) continuing damage even after cessation of irradiation in testes

A comparative study of total body irradiation as a method of inducing granulocyte depletion in mice

International Nuclear Information System (INIS)

Bogman, M.J.J.T.; Cornelissen, I.M.H.A.; Berden, J.H.M.; Jong, J. de; Koene, R.A.P.

1984-01-01

Since conventional methods of inducing depletion of polymorphonuclear granulocytes (PMNs) in mice, such as treatment with cytostatic drugs and anti-PMN sera, proved to be insufficient to induce a stable PMN depletion for several days, and were accompanied by considerable toxic side effects, we induced neutrophil depletion in mice by total body irradiation (TBI) in a single dose of 6.0 Gy (600 rads.) at a dose rate of 0.20 Gy/min. This treatment reduced the number of PMNs in the peripheral circulation to values below 150/μl from day 3-10 after irradiation. The number of lymphocytes fell simultaneously. Platelet counts remained above 60% of normal values during the first 7 days after irradiation. Complement levels were not significantly affected by TBI. The results show that TBI of 6.0 Gy induces pronounced and stable PMN depletion in mice for at least 7 days. Furthermore, under an aseptic regimen the mice can be kept in good condition and losses are less than 5%. (Auth.)

Recovery of humoral immunity parameters in mice under a long-term action of tritium oxide

International Nuclear Information System (INIS)

Kirillova, E.N.; Man'ko, V.M.; Muksinova, K.N.

1986-01-01

Using the mice-males of the CBA line at the age of 10-12 weeks and body mass of 20-23 g the recovery value of quantitative and qualitative factors of humoral immunity under a long-term action of tritium oxide which has been injected during 6 months in the quantity of 370 kBq per 1g of body mass (cumulative dose 8.73 Gy). The long-term internal mice irradiation with tritium oxide resulted in marked devastation of central and peripheral organs of immune system. An earlier and complete recovery of cells quantity in the bone marrow and spleen, recover up to 50% in lymphnodes and minimum repopulation (from 10 to 20%) in thymus as compared with tested animals of the same age is pointed out. In experimental mice CFU 5 pool decrease in bone marrow and spleen is found. CFUs content in the spleen recovered up to the norm, whereas in the bone marrow it constituted not more than 55% of the control. Deep function injury of V-lymphocyte and T - helper precursors the activity of which has not recovered during the whole observation period. The long-term tritium oxide intake lead to antibodies production suppression (by 30-50%), the tendency to the decrease of antibody formation of these animals has been conserved up to the end of life. The functional activity of T - suppressors in humoral response to thymus-dependent antigen during the remote periods upon long-term irradiation decreased more than twice

Immunomodulatory effects of ultraviolet B irradiation on atopic dermatitis in NC/NGA mice

International Nuclear Information System (INIS)

Yasuko Mutou; Shuji Kojima; Yuko Ibuki

2007-01-01

Complete text of publication follows. Background: Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with severe itching which occurs primarily in childhood. Overexpression of serum IgE are also a characteristic feature in many patient. Furthermore, Th2-type T cell cytokine, such as IL-4, IL-5, and Il-10, are produced in AD lesions. Recently, ultraviolet B (UVB) irradiation may increase according to depletion of the ozone layer. Furthermore, phototherapy is used to treat AD patient, but the mechanism involved is unknown. In this study, we investigated whether UVB irradiation influences atopic dermatitis in the NC/Nga mouse model. Methods: The mice were separated into 3 groups, control, AD-control (immunized with mite antigens), and AD + UVB-irradiated (immunized with mite antigens and UVB irradiation) groups. The mice of the irradiation group were exposed to 1 kJ/m 2 /day twice a week from 6 to 12 weeks of age. Animals of the control and AD-control groups were shaved, but not irradiated. Results: In the AD + UVB-irradiated group, the atopy score, ear thickness, and total IgE were increased in comparison with the AD-control group. On day 40, the levels of IL-4, IL-5, and IL-10 in the spleen lymphocytes were significantly increased compared with the AD-control group, resulting in a marked decrease of the IFN-Γ/IL-4 ratio compared with the AD-control group. In addition, the levels of IL-6, TNF-α, and NO X production by peritoneal macrophages were significantly elevated. Conclusion: These results indicate that UVB irradiation promotes the development of AD-like symptoms in NC/Nga mice, with an increased inflammatory response owing to increases of both IgE and NO X . In addition, systemic immune responses to local UVB were observed. It is possible that upstream proteins involved in IL-4, IL-5, IL-6, IL-10, and TNF-α, and NO X production play roles in the UVB-induced inflammatory responses. Our results also suggest that sunlight may aggravate the

Whole body proton irradiation causes acute damage to bone marrow hematopoietic progenitor and stem cells in mice.

Science.gov (United States)

Chang, Jianhui; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

2017-12-01

Exposure to proton irradiation during missions in deep space can lead to bone marrow injury. The acute effects of proton irradiation on hematopoietic stem and progenitor cells remain undefined and thus were investigated. We exposed male C57BL/6 mice to 0.5 and 1.0 Gy proton total body irradiation (proton-TBI, 150 MeV) and examined changes in peripheral blood cells and bone marrow (BM) progenitors and LSK cells 2 weeks after exposure. 1.0 Gy proton-TBI significantly reduced the numbers of peripheral blood cells compared to 0.5 Gy proton-TBI and unirradiated animals, while the numbers of peripheral blood cell counts were comparable between 0.5 Gy proton-TBI and unirradiated mice. The frequencies and numbers of LSK cells and CMPs in BM of 0.5 and 1.0 Gy irradiated mice were decreased in comparison to those of normal controls. LSK cells and CMPs and their progeny exhibited a radiation-induced impairment in clonogenic function. Exposure to 1.0 Gy increased cellular apoptosis but not the production of reactive oxygen species (ROS) in CMPs two weeks after irradiation. LSK cells from irradiated mice exhibited an increase in ROS production and apoptosis. Exposure to proton-TBI can induce acute damage to BM progenitors and LSK cells.

Hemopoiesis in bone marrow of lethally irradiated mice

International Nuclear Information System (INIS)

Viktora, L.; Zoubkova, M.; Urbankova, J.

1976-01-01

A percentual representation of individual types of cells and their share of the restoration of hemopoiesis in bone marrow was observed on the 9th, 12th, 16th and 20th days following transplantation of bone marrow cells to letally irradiated mice. Myelopoiesis was ascertained which on the 20th day after transplantation became the dominant constituent and reached peak level around the 16th day after transplantation. The examination further showed that with regard to the period of irradiation and transplantation the erythropoiesis in bone marrow culminates on the 9th day after the transplantation and that normal values are quickly restored. On the 2ath day myelopoiesis and lymphopoiesis come close to values in normal bone marrow

Effect of tocopherol-monoglucoside (TMG), a water-soluble glycosylated derivate of vitamin E, on hematopoietic recovery in irradiated mice

International Nuclear Information System (INIS)

Cherdyntseva, N.; Shishkina, A.; Butorin, I.; Gervas, P.

2005-01-01

A preparation of alpha-tocopherol monoglucoside (TMG) administered intraperitoneal (i.p.) at a dose of 600 mg/kg immediately after whole body gamma irradiation was examined for its radioprotective efficacy towards bone marrow and peripheral blood nucleated cells. When mice received X-rays at a dose of 5, 6 Gy, a marked decrease in bone marrow karyocytes and a reduction of peripheral leukocytes within the early post-irradiated period were observed. However these changes were attenuated in TMG-treated mice. Significant protection of blood lymphocytes was found for the TMG group of mice. The return to normal value of the reduced blood leukocyte count starting from the 8th day was more rapid in TMG-treated mice than in untreated irradiated mice. TMG administration was found to enhance hematopoietic recovery, as measured by the exceeded nucleated bone marrow cell count due to elevated amount of both lymphoid and granulocytic elements in the TMG-group, in comparison with that of both control irradiated and non-irradiated animals. These findings indicate that the radioprotective effect of TMG is apparently realized through its influence on hematopoietic system. (author)

Associations between tumor types in irradiated BALB/c female mice

International Nuclear Information System (INIS)

Storer, J.B.

1982-01-01

Associations between pairs of 12 different tumor types were estimated for a population of over 3800 irradiated BALB/c female mice. The associations were adjusted for age and radiation dose. Of the 66 pairs of tumor types, 21 showed significant positive or negative associations. Of these, 8 were considered to be spurious, principally because one or both of the tumors was rapidly lethal, leading to an apparent negative association. Six of the remaining 13 significant associations involed tumors of endocrine organs or tumors known to be endocrine related. Six others involved associations between lung, vascular tissue, or reticular tissue tumors, and tumors of endocrine organs. The remaining and highly negative association was between reticulum cell sarcomas and other lymphomas and leukemias. It was concluded that in irradiated female mice of this strain, at least, tumors are not independent and that alterations in host factors (principally endocrine) lead to animals developing both tumors (positive associations) or to one tumor but not the other (negative associations)

Schistosoma mansoni: quantitative aspects of the fertility and survival of worms obtained from irradiated cercariae (3 Krad), in mice

International Nuclear Information System (INIS)

Sa Cardoso, G. de; Coelho, P.M.Z.

1990-01-01

The effect of gamma irradiation on the fertility of female mice, as well as the survival of worms in their portal system, have been observed in four groups of outbred albino mice (Mus musculus), experimentally infected with ca 450 cercariae of Schistosoma mansoni (LE and SJ strains), by transcutaneous route. The cercariae used were a) non-irradiated (control groups), and b) irradiated with 3 Krad of gamma irradiation (Co-60). From the 33 rd day on, some stability in the population of surviving worm could be observed. This population remained constant till the end of the observation period (90 th day), notedly in relation to the LE strain . Thus, it was concluded that gamma irradiation (at the dose of 3 Krad) is able to hinder the worm egg production in 98.1% of the infected mice. Further, it was observed that the few detected eggs were dead. Females were found to be more resistant to irradiation. The irradiation effect on the mortality of male worms was statistically significant scarcely from the 61 st day on. The long period of permanence of the sterile adult irradiated worms in the portal system of mice and their probable involvement in the development of immuno-protection (the so-called concomitant immunity, without the immuno-pathological involvements for the host) are here discussed. (author)

The protective effect of Royal Jelly against the hemopoiesis dysfunction in X-irradiated mice

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Emori, Yutaka; Oka, Hideki; Ohya, Osamu; Tamaki, Hajime; Hayashi, Yoshiro [Zeria Pharmaceutical Co., Ltd., Konan, Saitama (Japan). Central Research Laboratories; Nomoto, Kikuo

1998-02-01

The protective effect of Royal Jelly (RJ) against the hemopoietic dysfunction in whole body X-irradiated C57BL/6 mice was investigated. When RJ (1.0 g/kg, po or 0.5 g/kg, ip) was administered every day beginning two weeks before X-irradiation (10 Gy), a significant increase in the number of leukocytes and erythrocytes was observed in mice treated with RJ, as compared with X-irradiated control. In addition, the number of colony forming units in culture (CFU-C) of bone marrow cells or splenocytes was significantly increased in mice treated with RJ. Therefore, when granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) in peripheral blood was measured by ELISA kit, a significant increase in the amount of GM-CSF and IL-3 was observed. These results suggest that the protective effect of RJ against hemopoietic dysfunction could be expressed through an increase in the number of hemopoietic stem cells by the induction of hemopoietic factor such as GM-CSF and IL-3. (author)

Reticuloendothelial neoplasms in C57 black mice after fast-neutron irradiation at low dosage

International Nuclear Information System (INIS)

Mewissen, D.J.; Rust, J.H.

1976-01-01

In many inbred strains of mice the modulation of the basic control tumor pattern by ionizing radiation is operative primarily on the reticular tissue. This phenomenon seems more productive with high linear energy transfer radiation, particularly neutrons. The results reported in this paper are based on a total of 1963 C57 Black mice, subline 6, of either sex. From each litter animals were randomly assigned to control and treatment groups and were neutron-irradiated at 3.2, 4.5, 6.3, 8.8, and 12.3 rads of single exposure. In male and female irradiation groups, incidence rates for lymphocytic lymphomas were sharply decreased by neutron irradiation at all dose levels. In reticulum-cell sarcomas an interesting contrast was observed. First, the tumor type shifted almost entirely from type A to type B. Second, all specific incidence rates were markedly increased by radiation, both for male and female mice at all dose levels. Our data suggest the existence of an intercompetitive process triggered or accelerated by radiation

Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy

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Lisa Y. Pang

2016-01-01

Full Text Available Cyclooxygenase-2 (COX-2 is an inducible form of the enzyme that catalyses the synthesis of prostanoids, including prostaglandin E2 (PGE2, a major mediator of inflammation and angiogenesis. COX-2 is overexpressed in cancer cells and is associated with progressive tumour growth, as well as resistance of cancer cells to conventional chemotherapy and radiotherapy. These therapies are often delivered in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during treatment intervals, leading to repopulation of the tumour and limiting the effectiveness of the treatment. Tumour cell repopulation is a major cause of treatment failure. The central dogma is that conventional chemotherapy and radiotherapy selects resistant cancer cells that are able to reinitiate tumour growth. However, there is compelling evidence of an active proliferative response, driven by increased COX-2 expression and downstream PGE2 release, which contribute to the repopulation of tumours and poor patient outcome. In this review, we will examine the evidence for a role of COX-2 in cancer stem cell biology and as a mediator of tumour repopulation that can be molecularly targeted to overcome resistance to therapy.

Residual injury to the hemopoietic microenvironment following sequential radiation and alkylating agents

International Nuclear Information System (INIS)

Wathen, L.M.K.

1981-01-01

To assess the hemopoietic impact following combined therapy, mice received intraperitoneal doses of cyclophosphamide one week after 1500 rad leg irradiation. This treatment inhibited repopulation of endogenous nucleated cells to less than 60% of normal. Leg irradiation alone repressed the repopulation to about 75% of normal and cyclophosphamide alone suppressed to 80% of normal. Differential marrow counts revealed that marrow stromal cells were suppressed to less than 30% normal for 3 months following combined modality treatment. Studies were initiated to determine whether busulfan, an alkylating agent known to produce aplastic anemia, would cause microenvironmental damage similar to that seen following cyclophosphamide. The mice received intraperitoneal doses of busulfan one week after 1500 rad leg irradation. In general, the pattern of hemopoietic suppression was similar to that following sequential radiation and cyclophosphamide. However, at 4 and 6 months post-irradiation, the busulfan treated mice had a more severe suppression of CFU-S, CFU-C, and marrow stromal cells than mice treated with cyclophosphamide alone. In addition, an excessive number of myeloid blast cells and a severe erythroid depletion suggested that the BU-treated mice were preleukemic. Vascular patency was studied by injecting 51 Cr labeled autologous red blood cells into mice treated with the radiation and busulfan regimen. Combined modality therapy inhibited the ingress of 51 Cr labeled erythrocytes into the irradiated femur but either modality alone did not cause inhibition. It was concluded that a portion of the microenvironmental defect seen in the combined radiation and alkylating agent studies was the result of microvascular damage and that a portion was due to marrow stromal cell insufficiency

Flt3 ligand-eGFP-reporter expression characterizes functionally distinct subpopulations of CD150+ long-term repopulating murine hematopoietic stem cells.

Science.gov (United States)

Tornack, Julia; Kawano, Yohei; Garbi, Natalio; Hämmerling, Günter J; Melchers, Fritz; Tsuneto, Motokazu

2017-09-01

The pool of hematopoietic stem cells (HSCs) in the bone marrow is a mixture of resting, proliferating, and differentiating cells. Long-term repopulating HSCs (LT-HSC) are routinely enriched as Lin - Sca1 + c-Kit + CD34 - Flt3 - CD150 + CD48 - cells. The Flt3 ligand (Flt3L) and its receptor Flt3 are important regulators of HSC maintenance, expansion and differentiation. Using Flt3L-eGFP reporter mice, we show that endogenous Flt3L-eGFP-reporter RNA expression correlates with eGFP-protein expression. This Flt3L-eGFP-reporter expression distinguishes two LT-HSC populations with differences in gene expressions and reconstituting potential. Thus, Flt3L-eGFP-reporter low cells are identified as predominantly resting HSCs with long-term repopulating capacities. In contrast, Flt3L-eGFP-reporter high cells are in majority proliferating HSCs with only short-term repopulating capacities. Flt3L-eGFP-reporter low cells express hypoxia, autophagy-inducing, and the LT-HSC-associated genes HoxB5 and Fgd5, while Flt3L-eGFP-reporter high HSCs upregulate genes involved in HSC differentiation. Flt3L-eGFP-reporter low cells develop to Flt3L-eGFP-reporter high cells in vitro, although Flt3L-eGFP-reporter high cells remain Flt3L-eGFP-reporter high . CD150 + Flt3L-eGFP-reporter low cells express either endothelial protein C receptor (EPCR) or CD41, while Flt3L-eGFP-reporter high cells do express EPCR but not CD41. Thus, FACS-enrichment of Flt3/ Flt3L-eGFP-reporter negative, Lin - CD150 + CD48 - EPCR + CD41 + HSCs allows a further 5-fold enrichment of functional LT-HSCs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Restorative effect of exogenous RNA on the intestinal crypts in mice after abdominal γ-irradiation

International Nuclear Information System (INIS)

Zeng Guiying; Han Shichen; Liu Aiping; Xie Xuejun; Zhou Yuankai

1995-01-01

The author's previous investigation revealed a restorative effect of exogenous nucleic acids on the intestinal crypt in mice after abdominal γ-irradiation. In the article, the factors influencing the restorative effect of exogenous RNA on the intestinal crypt in mice post-irradiation were studied. The results showed that: (a) RNAs from different sources all showed the crypt survival enhancement capability. (b) Bell-shaped curves correlating the crypt survival fraction and RNA doses were obtained, with the optimal doses for different routes of administration estimated. (c) Comparing the different routes of RNA administration, the intravenous injection seemed to be the most effective. (d) An exponential relationship between the crypt survival fraction and the post-irradiation time of RNA administration was found. The earlier the administration, the more effective it was. (e) Administration of RNA merely once within 6h after irradiation, the increases of crypt survival fraction was statistically significant when compared with that of the irradiated control

Investigation of bacterial repopulation after sinus surgery and perioperative antibiotics.

Science.gov (United States)

Hauser, Leah J; Ir, Diana; Kingdom, Todd T; Robertson, Charles E; Frank, Daniel N; Ramakrishnan, Vijay R

2016-01-01

Endoscopic sinus surgery (ESS) enjoys high success rates, but repopulation with pathogenic bacteria is 1 of the hallmarks of poorer outcomes. There are many hypothesized sources of repopulating bacteria; however, this process remains largely unexplored. This study examined changes in the sinus microbiome after ESS and medical therapies to identify potential sources for postsurgical microbial repopulation. Samples from the anterior nares, ethmoid sinus, and nasopharynx were taken at the time of surgery from 13 subjects undergoing ESS for chronic rhinosinusitis (CRS). Patients were treated postoperatively with 2 weeks of oral antibiotics and saline rinses. The ethmoid sinus was sampled at 2 and 6 weeks postoperatively; microbiota were characterized using quantitative polymerase chain reaction (qPCR) and 16S ribosomal RNA (rRNA) gene sequencing. The Morisita-Horn beta-diversity index (M-H) was used to compare similarity between samples. The bacterial burden of the ethmoid was higher 2 weeks postoperatively than 6 weeks postoperatively (p = 0.01). The 6-week samples most closely represented the anterior nares and ethmoid at surgery (M-H = 0.58 and 0.59, respectively), and were least similar to the nasopharynx (M-H = 0.28). Principal coordinates analysis (PCoA) plots illustrate that the ethmoid microbiota temporarily shifted after surgery and antibiotics but returned toward baseline in many subjects. Bacterial communities colonizing the ethmoid 6 weeks postoperatively were most similar to anterior nasal cavity and pretreatment sinus microbial profiles, indicating a high degree of resilience in the sinonasal microbiome of most subjects. Interestingly, surgery and postoperative antibiotic therapy does not appear to reduce bacterial burden, but rather, shifts the microbial consortia. © 2015 ARS-AAOA, LLC.

Studies on immunity to Schistosoma mansoni in vivo: whole-body irradiation has no effect on vaccine-induced resistance in mice

International Nuclear Information System (INIS)

Vignali, D.A.A.; Bickle, Q.D.; Taylor, M.G.

1988-01-01

Actively immunized mice, whole-body irradiated with 650 or 525 rad., manifested comparable levels of resistance to Schistosoma mansoni compared with unirradiated, immunized mice in spite of a marked reduction in circulating leucocytes and platelets, and despite an abrogation of delayed-type hypersensitivity (DTH) (Type IV) reponse to schistosomular antigens. However, limited histopathological comparison of lung sections from irradiated and unirradiated mice 7 days post-challenge showed that cellular reactions ('foci') around parasites were similar in size and cellular composition except that in irradiated mice, eosinophils were poorly represented both in the foci and in lung tissue in general. Neither presumed immune complex-mediated (Type III, Arthus reaction) hypersensitivity nor serum anti-schistosomulum extract antibody levels were affected. The pattern of 125 I-labelled schistosomular surface antigens immunoprecipitated with serum from irradiated and unirradiated mice was essentially similar. These results are consistent with antibody playing an important role in vaccine-induced immunity in mice but suggest that radiosensitive T cell function and radiosensitive cells, such as platelets and polymorphonuclear cells, including eosinophils, may not be essential. (author)

Evaluation of reduced allergenicity of irradiated peanut extract using splenocytes from peanut-sensitized mice

Energy Technology Data Exchange (ETDEWEB)

Oh, Sejo; Jang, Da-In [Department of Pediatrics, Ajou University School of Medicine, Suwon 442-749 (Korea, Republic of); Lee, Ju-Woon; Kim, Jae-Hun; Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Lee, Soo-Young [Department of Pediatrics, Ajou University School of Medicine, Suwon 442-749 (Korea, Republic of)], E-mail: jsjs87@ajou.ac.kr

2009-07-15

Peanut (PN) allergy is one of the most serious forms of IgE-mediated food hypersensitivity. Gamma irradiation has been widely used for the preservation of food. The results of our previous studies showed that the IgE-binding capacity to several antigens were profoundly reduced after gamma irradiation. In this study, we evaluated the changes of allergenecity and cytokine production profiles after exposure of irradiated PN extract in a PN-allergy mouse model. Mice were sensitized to PN extract by intragastric administration on days 0, 1, 2, and 7, and then challenged on day 21. Four weeks later, we evaluated the cytokine production patterns and proliferation responses of splenocytes that were stimulated with intact PN extract, compared to 10 and 50 kGy irradiated PN extract. When the cells were stimulated with 10 kGy of irradiated PN extract, a higher level of production of IFN-{gamma} and IL-10 cytokines was observed. However, stimulation with 50 kGy of irradiated PN extract resulted in a higher level of production of only IFN-{gamma} cytokines. In addition, the Th1/Th2 ratio increased in response to treatment with gamma-irradiated PNs. The results of this study show that the allergenicity of PN extracts could be reduced by gamma irradiation which caused downregulation of Th2 lymphocyte activity in the PN-sensitized mice.

Evaluation of reduced allergenicity of irradiated peanut extract using splenocytes from peanut-sensitized mice

International Nuclear Information System (INIS)

Oh, Sejo; Jang, Da-In; Lee, Ju-Woon; Kim, Jae-Hun; Byun, Myung-Woo; Lee, Soo-Young

2009-01-01

Peanut (PN) allergy is one of the most serious forms of IgE-mediated food hypersensitivity. Gamma irradiation has been widely used for the preservation of food. The results of our previous studies showed that the IgE-binding capacity to several antigens were profoundly reduced after gamma irradiation. In this study, we evaluated the changes of allergenecity and cytokine production profiles after exposure of irradiated PN extract in a PN-allergy mouse model. Mice were sensitized to PN extract by intragastric administration on days 0, 1, 2, and 7, and then challenged on day 21. Four weeks later, we evaluated the cytokine production patterns and proliferation responses of splenocytes that were stimulated with intact PN extract, compared to 10 and 50 kGy irradiated PN extract. When the cells were stimulated with 10 kGy of irradiated PN extract, a higher level of production of IFN-γ and IL-10 cytokines was observed. However, stimulation with 50 kGy of irradiated PN extract resulted in a higher level of production of only IFN-γ cytokines. In addition, the Th1/Th2 ratio increased in response to treatment with gamma-irradiated PNs. The results of this study show that the allergenicity of PN extracts could be reduced by gamma irradiation which caused downregulation of Th2 lymphocyte activity in the PN-sensitized mice.

Effects of low dose γ-rays irradiation on yield of tumor-infiltrating lymphocytes in mice

International Nuclear Information System (INIS)

Zou Huawei; Su Liaoyuan; Tian Hailin

1998-01-01

It is confirmed that low dose irradiation can inhibit tumor growth. In order to know tumor growth inhibiting mechanism, the changes of tumor-infiltrating lymphocytes (TIL) were investigated after exposing to tumor-bring mice. The mice were exposed to different doses, then , EAC cells were transplanted at the 3,6,9 and 24h hour. Ten days later TILs increased obviously caused by of 5-10 cGy γ-rays irradiation. The most obvious increasing occurred in the group in which cells was exposed irradiation for 6 hours at 10 cGy dose. A low dose radiation can make the yield of TILs increased. I might be correlated to the mechanism of tumor growth inhibiting

Effects of AET, MEA, or 5-HT treatment before X-irradiation of pregnant C57B mice

International Nuclear Information System (INIS)

Mazur, L.

1985-01-01

C57B mice were either whole body X-irradiated with a dose of 200 R or, 15 minutes before X-radiation injected with AET, MEA, or 5-HT, in a dose of 40 mg/kg of body weight, on the first day of gestation. Uterine contents were examined on the nineteenth day of pregnancy. The number of corpora lutea was assumed as 100% and the percentage values of live and dead foetuses, resorptions, and non-implanted embryos were calculated. The percentage ratio of females with live foetuses in the uterus, in relation to the total number of those with a vaginal plug was also determined. X-irradiation of pregnant mice influenced the embryonic survival. As compared with controls, in only X-irradiated mice a lower percentage value of live foetuses and higher percentage values of non-implanted embryos and resorptions were found. One dead foetus was only observed in X-irradiated females. Percentage value of X-irradiated females with live foetuses was lower than that of control ones. High mortality of embryos occurred more often before than after the implantation of blastocysts. The percentage value of non-implanted embryos was higher than that of resorptions. AET, MEA, and 5-HT when injected to mice before their X-irradiation acted as radioprotectors. The strongest radioprotective effect was obtained following AET administration, intermediate after 5-HT treatment and the weakest one when MEA was injected. (orig.) [de

The effect of whole body or total-head x irradiation of the metallophilic cells in the mice spleen

International Nuclear Information System (INIS)

Sasaki, Osamu; Matsueda, Yasutoshi; Mizuguchi, Hiroshi; Moriguchi, Kenzo; Ogata, Kunitoshi; Sugie, Tsuneto

1984-01-01

The purpose of this paper is to clarify morphological changes of the reticuloendothelial cells in the spleen following X-irradiation by Katsura's silver impregnation method. The animals used in this experiment were ddN female mice weighing 20 to 25g. The mice were given X-irradiation to the total-head (1,500R) or whole body (300R). The metallophilic cells in the spleen of control mice were of the small foamy type in the follicle, the large stellate type in the marginal metallophils, the small branching type in the marginal zone and the small foamy or round type in the red pulp, respectively. The metallophilic cells decreased immediately after whole body irradiation and the number of cells returned to normal in from 10 to 14 days. On the other hand, the number of the metallophilic cells in the follicle and the perifollicular region increased immediately after total-head X-irradiation. This state continued for several days. In the marginal zone and red pulp, the number of amoebian type cells appeared from 24 hours after irradiation and the number of cells in total-head irradiation group were more clearly distinguishable than in the whole body irradiated group. (author)

Growth of Theileria annulata and Theileria parva macroschizont-infected bovine cells in immunodeficient mice: effect of irradiation and tumour load on lymphocyte subsets

Energy Technology Data Exchange (ETDEWEB)

Fell, A.H.; Preston, P.M. (Edinburgh Univ. (United Kingdom))

1992-07-01

Bovine cells infected with macroschizonts of the protozoan parasites Theileria annulata and Theileria parva formed solid tumours when injected into irradiated Balb/c and irradiated Balb/c nude mice. T. annulata tumours grew more vigorously than T. parva tumours, when initiated with similar doses of infected cells in mice exposed to the same doses of gamma-irradiation. In irradiated Balb/c mice, tumours of both species of parasites began to regress 2-3 weeks after injection of cells but grew without regression in irradiated Balb/c nude mice. Haemorrhage and necrosis of tumours, induced by macrophages and neutrophils, were seen in both mouse strains but were insufficient to cause regression in Balb/c nude mice. Theileria-infected bovine cells failed to establish in C57 beige mice, which lack functional natural killer (NK) cells. Flow cytometry, using monoclonal antibodies to murine leukocyte/lymphocyte antigens, showed that the radiation dose required to allow establishment of T. annulata tumours in Balb/c mice caused a severe depletion of splenic lymphocytes. B cells, helper T and cytotoxic T cells showed differing levels of susceptibility to irradiation. (Author).

Growth of Theileria annulata and Theileria parva macroschizont-infected bovine cells in immunodeficient mice: effect of irradiation and tumour load on lymphocyte subsets

International Nuclear Information System (INIS)

Fell, A.H.; Preston, P.M.

1992-01-01

Bovine cells infected with macroschizonts of the protozoan parasites Theileria annulata and Theileria parva formed solid tumours when injected into irradiated Balb/c and irradiated Balb/c nude mice. T. annulata tumours grew more vigorously than T. parva tumours, when initiated with similar doses of infected cells in mice exposed to the same doses of gamma-irradiation. In irradiated Balb/c mice, tumours of both species of parasites began to regress 2-3 weeks after injection of cells but grew without regression in irradiated Balb/c nude mice. Haemorrhage and necrosis of tumours, induced by macrophages and neutrophils, were seen in both mouse strains but were insufficient to cause regression in Balb/c nude mice. Theileria-infected bovine cells failed to establish in C57 beige mice, which lack functional natural killer (NK) cells. Flow cytometry, using monoclonal antibodies to murine leukocyte/lymphocyte antigens, showed that the radiation dose required to allow establishment of T. annulata tumours in Balb/c mice caused a severe depletion of splenic lymphocytes. B cells, helper T and cytotoxic T cells showed differing levels of susceptibility to irradiation. (Author)

Effects of irradiation at different dose rates on the onset of type I diabetes in model mice

International Nuclear Information System (INIS)

Nomura, Takashi; Sakai, Kazuo

2003-01-01

We previously demonstrated that low-dose irradiation (0.5 Gy) increased the level of antioxidants and decreased the level of lipid peroxide in normal mice. We also found that 0.5 Gy-irradiation of NOD mice suppressed the onset of type I diabetes. These results were obtained by the irradiation at high dose rate. The aim of the present study is to examine the effects at the low dose rate. The mice were acutely irradiated with 0.5 Gy of X-rays (300 kVp) at 94.2 Gy/hr at 10, 11, 12, 13 or 14 weeks of age, or chronically irradiated with 0.5 Gy of 137 Cs γ-rays at 0.95 mGy/hr starting at 10,11,12,13 or 14 weeks of age. When irradiated at 12th week with the high dose rate X-rays, the onset of diabetes suppressed, and the increase in the specific activity of superoxide dismutase (SOD) in pancreas was observed. On the other hand, the low dose rate γ-rays delivered from 12th week of age to 14th was less effective in the suppression of the incidence of diabetes than the high dose rate X-rays at the 12-14 weeks of age. Furthermore, the significant increase in pancreatic SOD activity was not observed after the low dose irradiation. Splenic macrophage activities of superoxide generation were not affected by the high dose rate irradiation nor the low dose rate irradiation. (author)

Evaluation of caffeine as a radioprotector in gamma-irradiated C57BL/6N male mice

Energy Technology Data Exchange (ETDEWEB)

Kim, Ji Hyang; Yoon, Yong Dal [Hanyang University, Seoul (Korea, Republic of); Kim, Jin Kyu [KAERI, Taejon (Korea, Republic of)

2002-10-01

Caffeine is the main psychoactive ingredient of coffee, tea, even colas with a high frequency of concurrent use in humans. Caffeine has been recently reported as a scavenger of hydroxyl radical in millimolar levels and a potential radioprotector in chronically exposed rodent. This study was performed to investigate the functional radioprotection of caffeine in gamma-irradiated mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administrated 80 mg/ kg body weight by i.p injection, a single exposure, at 1 hour before irradiation. The remaining mice were kept as sham controls. At 6 hours after irradiation, we measured the body and organ weight, collected serum, and testes were removed and processed for paraffin sections and isolation of total RNA. Hormonal analysis was performed by means of radioimmunoassay (RIA) in serum. Semiquantitative reverse transcription-reverse chain reaction (RT-PCR) was used to evaluate the expression kinetics of the apoptotic genes after irradiation. The weight of body and organ and H-E stained slide did not show a difference between groups. The circulating testosterone significantly decreased in irradiated group. RT-PCR data represented that the expression of Fas antigen, p21, p53, bax, and bcl2 related radiation-induced apoptosis showed the specific patterns comparable to that of caffeine-untreated group. Specially, bax mRNA dramatically increased in irradiated group, except caffeine-treated irradiated. Taken together, caffeine can protect an early apoptotic initiation against gamma radiation and may act as a radioprotector.

Evaluation of caffeine as a radioprotector in gamma-irradiated C57BL/6N male mice

International Nuclear Information System (INIS)

Kim, Ji Hyang; Yoon, Yong Dal; Kim, Jin Kyu

2002-01-01

Caffeine is the main psychoactive ingredient of coffee, tea, even colas with a high frequency of concurrent use in humans. Caffeine has been recently reported as a scavenger of hydroxyl radical in millimolar levels and a potential radioprotector in chronically exposed rodent. This study was performed to investigate the functional radioprotection of caffeine in gamma-irradiated mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administrated 80 mg/ kg body weight by i.p injection, a single exposure, at 1 hour before irradiation. The remaining mice were kept as sham controls. At 6 hours after irradiation, we measured the body and organ weight, collected serum, and testes were removed and processed for paraffin sections and isolation of total RNA. Hormonal analysis was performed by means of radioimmunoassay (RIA) in serum. Semiquantitative reverse transcription-reverse chain reaction (RT-PCR) was used to evaluate the expression kinetics of the apoptotic genes after irradiation. The weight of body and organ and H-E stained slide did not show a difference between groups. The circulating testosterone significantly decreased in irradiated group. RT-PCR data represented that the expression of Fas antigen, p21, p53, bax, and bcl2 related radiation-induced apoptosis showed the specific patterns comparable to that of caffeine-untreated group. Specially, bax mRNA dramatically increased in irradiated group, except caffeine-treated irradiated. Taken together, caffeine can protect an early apoptotic initiation against gamma radiation and may act as a radioprotector

Macroarray analysis of gene expression in hematopoietic tissues from mice continuously irradiated by low dose-rate ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Saitou, Mikio; Nakamura, Shingo; Shirata, Katsutoshi; Yanai, Takanori; Izumi, Jun; Sugihara, Takashi; Tanaka, Satoshi; Tanaka, Kimio; Otsu, Hiroshi; Sato, Fumiaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan)

2002-07-01

We found that the number of hematopoietic progenitor cells in bone marrow and spleen from 4 - 8 Gy-irradiated mice decreased about 50%, in spite of no change in the number of peripheral blood cells. To evaluate the effects of chronic irradiation by low dose-rate ionizing radiation on the gene expression in mice hematopoietic cells from bone marrow and spleen, the RNA expressions of more than 500 genes such as cytokine genes and oncogenes were measured on the membranes by the RNA macroarray analysis method at accumulated doses at 4.7 and 8 Gy in specific-pathogen-free (SPF) C3H/HeN female mice irradiated by {sup 137}Cs {gamma}-rays with the dose rate of 20 mGy/day. The RNA macroarray analysis in spleens from 8 Gy-irradiated mice showed that the expressions in 16 genes including noggin were more than 1.5 times larger than that of control, while those in 64 genes including shh (sonic hedgehog) and BMP-4 (bone morphogenesis protein 4) were more than 1.5 times smaller than that of control. (author)

Quantitative changes in the arterial blood gases of mice following localized irradiation of the lungs

International Nuclear Information System (INIS)

Siemann, D.W.; Hill, R.P.

1983-01-01

The arterial pH and partial pressures of oxygen (PaO 2 ) and carbon dioxide (PaCO 2 ) were evaluated in LAF1 mice 15 and 38 weeks after localized irradiation of the animals' thoraxes. Graded radiation doses of 900 to 1200 rad were administered. These doses resulted in 0 to 100% lethality by 26 weeks (180 days) after irradiation. At 15 weeks after treatment mice receiving radiation doses which would subsequently result in lethality (by 180 days) exhibited significant reductions in their PaO 2 and elevations in their PaCO 2 values, respectively. However, there was no clear dose-response relationship between blood gas values and radiation dose, which may reflect the animals' ability to compensate for their poor blood gas exchange by an increased breathing frequency. At 38 weeks after irradiation the blood gas values were abnormal in mice from groups which had normal blood gas values at Week 15 (and no fatalities by Week 26) but in which animal deaths had occurred between Weeks 26 and 38. These data therfore indicated (i) that abnormal blood gas values occurred in the mice prior to fatalities resulting from the acute radiation pneumonitis syndrome and (ii) that mice surviving the initial radiation pneumonitis phase could still succumb to progressive pulmonary toxicity which was reflected by the increasing levels of animal lethality and altered blood gas tensions at the later times

Protective effect of zinc against lethality of the irradiated mice

International Nuclear Information System (INIS)

Matsubara, J.; Inada, T.; Machida, K.

1982-01-01

The effects of adding 1000 ppm Zn in the drinking water 10 days before gamma irradiation (562 - 1000 rad) of mice were studied. The mice which had received zinc had a lower mortality rate and a longer survival time compared to the controls. The LD 50 of gamma radiation was 690 rad in the control group and 770 rad in the zinc group. Zinc added to the culture medium of human melanoma cells did not shown any change in radiosensitivity; thus the radioprotective effect of zinc appears to work at the whole body level. (U.K.)

Safety evaluation of the ethyl acetate extract on irradiated tea parasite: Acute toxicity study on mice

International Nuclear Information System (INIS)

Hendig Winarno

2011-01-01

Many studies of the pharmacological efficacy of tea parasite and the use of ionizing radiation for decontamination of microbes and extending shelf life have been reported, but there is no information on its safety, such as the acute toxicity. In this study, the acute toxicity of two ethyl acetate extracts from unirradiated and irradiated (irradiation dose of 10 kGy) tea parasites Scurrula atropurpurea on Swiss Webster mice have been examined. The observation was done after the treatment of a single oral dose of ethyl acetate extract in various dose groups, i.e.: control (0 g/kg of mice body weight), D1 (0.625 g/kg), D2 (1.25 g/kg), D3 (2.5 g/kg) D4 (5 g/kg), D5 (10 g/kg) by observing the effect on behavioral response (pharmacological profile), the body weight gains and mortality until the day 14 th . At the last day, the observation of vital organs has also been done. The result showed that no acute toxicity was found in mice treated with a single oral dose of ethyl acetate extract from unirradiated tea parasite and irradiated tea parasite at the dose of 10 kGy. At the dose up to 10 g/kg (equivalent to 77.6 g of extract which administered to human), the normal body weight gains were observed in mice of all dose groups, no mice deaths in any of the dose groups, and no significant change (p > 0.05) in organ weights relative to the body weight i.e.: liver, spleen, kidneys, lung, heart, testes and seminal vesicle (for male), and ovaries and uterus (for female). The approximate lethal doses for male and female mice were determined to be higher than 10 g/kg of mice body weight. It is suggested that the treatment of ethyl acetate extract from unirradiated and irradiated tea parasites until dose up to 10 g/kg of mice body weight was still safe. (author)

Cellular and Behavioral Effects of Cranial Irradiation of the Subventricular Zone in Adult Mice

Science.gov (United States)

Lazarini, Françoise; Mouthon, Marc-André; Gheusi, Gilles; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Lamarque, Stéphanie; Abrous, Djoher Nora; Boussin, François D.; Lledo, Pierre-Marie

2009-01-01

Background In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear. Methodology/Principal Findings In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation. Conclusion/Significance These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces. PMID:19753118

Cellular and behavioral effects of cranial irradiation of the subventricular zone in adult mice.

Directory of Open Access Journals (Sweden)

Françoise Lazarini

2009-09-01

Full Text Available In mammals, new neurons are added to the olfactory bulb (OB throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear.In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation.These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces.

The effect of gamma-rays on the hemoglobin of whole-body irradiated mice

International Nuclear Information System (INIS)

Ashry, H.A.; Selim, N.S.; El-Behay, A.Z.

1994-01-01

Changes in the UV-visible absorption spectrum of mouse hemoglobin as a result of whole body irradiation were studied. White albino adult mice were exposed to a Cs-137 γ-source at a dose rate of 47.5 Gy/h to different absorbed dose values ranging from 1 to 8 Gy. Blood specimens were taken 24 h after irradiation. The UV-visible absorption spectra of hemoglobin of irradiated and control mice were measured in the wavelength range from 200 to 700 nm. The obtained results showed significant changes in the bands measured at 340 nm, in the Soret band measured at 410 nm, also, the α- and β-bands measured at 537 and 572 nm showed significant decrease in intensity with the absorbed dose increase. The absorbance measured at 630 nm showed no significant changes. The radiation effect on the animal hemoglobin was discussed on the basis of the obtained results. (Author)

Abrogation of genetically controlled resistance of mice to Treponema pallidum by irradiation

International Nuclear Information System (INIS)

Klein, J.R.; Monjan, A.A.; Hardy, P.H. Jr.; Cole, G.A.

1980-01-01

On intradermal infection, transient primary lesions, characteristic of those seen in naturally acquired human syphilis, can be produced regularly in some strains of mice but not others, indicating a genetic basis for host susceptibility. However strains of mice which normally fail to develop lesions, do so after exposure to ionising radiation. Here the importance of an intact immune system in the outcome of local infection is illustrated by the use of radiation-induced immunosuppression. The mice were exposed to lethal doses of total body irradiation from a 137 Ce source (137 rad per min), 850-1,050 rad depending on mouse strain. (UK)

Effect of prolonged irradiation by low dose-rate ionizing radiation on the hemopoiesis of mice

Energy Technology Data Exchange (ETDEWEB)

Yanai, Takanori; Shirata, Katsutoshi; Yamada, Yutaka; Saitou, Mikio; Izumi, Jun; Tanaka, Satoshi; Otsu, Hiroshi; Sato, Fumiaki [Institute for Environmental Sciences, Rokkasho, Aomori (Japan)

2000-07-01

For evaluation of effects of prolonged irradiation by low dose-rate ionizing radiation on the hemopoiesis of mice, SPF C3H/HeN female mice were irradiated with {sup 137}Cs {gamma}-rays with doses of 1-4 Gy at the dose rate of 20 mGy/22h-day. After irradiation, the number of hemopoietic cells contained in spleen was determined by the methods of CFU-S and CFU-GM assay, and the number of peripheral blood cells was counted. It was shown that the number of CFU-S colonies on day 12, which is in the earlier stage of differentiation, decreased as dose increased. No remarkable changes in the number of peripheral blood cells, however, were observed. (author)

The affect of bone marrow cell biomechanical characteristics to 6 Gy γ irradiation-injured mice

International Nuclear Information System (INIS)

Pu Xiaoyun; Chen Xiaoli; Pan Jing; Li Zhaoquan; Deng Jun; Huang Hui; Ye Yong

2004-01-01

Objective: To explore the change of bone marrow cell biomechanical characteristics in radiation-injured mice and the influencing factors. Methods: Male Kunming mice were exposed to total body irradiation of 6 Gy γ-rays from a 60 Co source. Electrophoresis, DPH probe-micropore filter, and adhesion rate methods were used to detect cell surface charge, membrane microviscosity, cell deformability, and cell adhesion, respectively. Results: The deformability, adhesiveness and cell surface charges of bone marrow cells (including hematopoietic cells and stromal cells) were dramatically decreased, but membrane microviscosity was obviously increased after irradiation on 1 d, 3 d and 7 d. Conclusion: The biomechanical characteristics of bone marrow cells are obviously changed after radiation injury. It might be one of the reasons of hematopoietic failure after irradiation. (authors)

Development of intraepithelial T lymphocytes in the intestine of irradiated SCID mice by adult liver hematopoietic stem cells from normal mice

International Nuclear Information System (INIS)

Yamagiwa, Satoshi; Seki, Shuhji; Shirai, Katsuaki; Yoshida, Yuhei; Miyaji, Chikako; Watanabe, Hisami; Abo, Toru

1999-01-01

Background/Aims: We recently reported the adult mouse liver to contain c-kit + stem cells that can give rise to multilineage leukocytes. This study was designed to determine whether or not adult mouse liver stem cells can generate intraepithelial T cells in the intestine as well as to examine the possibility that adult liver c-kit + stem cells originate from the fetal liver. Methods: Adult liver mononuclear cells, bone marrow (BM) cells, liver c-kit + cells or bone BM c-kit + cells of BALB/c mice were i.v. transferred into 4 Gy irradiated CB17/-SCID mice. In other experiments, fetal liver cells from Ly5.1 C57BL/6 mice and T cell depleted adult BM cells from Ly5.2 C57BL/6 mice were simultaneously transferred into irradiated C57BL/6 SCID mice (Ly5.2). At 1 to 8 weeks after cell transfer, the SCID mice were examined. Results: Not only BM cells and BM c-kit + cells but also liver mononuclear cells and liver c-kit + cells reconstituted γδT cells, CD4 + CD8 + double-positive T cells and CDiα + β - T cells of intestinal intraepithelial lymphocytes of SCID mice. Injection of a mixture of fetal liver cells from Ly5.1 C57BL/6 mice and adult BM cells from Ly5.2 C57BL/6 mice into Ly5.2 C57BL/6 SCID mice induced both Ly5.1 and Ly5.2 T cells, while also generating c-kit + cells of both Ly5.1 and Ly5.2 origins in the liver. Conclusions: Adult mouse liver stem cells were able to generate intestinal intraepithelial T cells of the SCID mice, and it is thus suggested that some adult liver stem cells may indeed be derived from the fetal liver. (au)

Inhibition of cyclobutane pyrimidine dimer formation in epidermal p53 gene of UV-irradiated mice by alpha-tocopherol

International Nuclear Information System (INIS)

Chen, W.; Barthelman, M.; Martinez, J.; Alberts, D.; Gensler, H.L.

1997-01-01

Mutations or alterations in the p53 gene have been observed in 50-100% of ultraviolet light (UV)-induced squamous cell carcinoma in humans and animals. Most of the mutations occurred at dipyrimidine sequences, suggesting that pyrimidine dimers in the p53 gene play a role in the pathogenesis of cutaneous squamous cell carcinoma. We previously showed that topical alpha-tocopherol prevents UV-induced skin carcinogenesis in the mouse. In the present study we asked whether topical alpha-tocopherol reduces the level of UV-induced cyclobutane pyrimidine dimers in the murine epidermal p53 gene. Mice received six dorsal applications of 25 mg each of alpha-tocopherol, on alternate days, before exposure to 500 J/m2 of UV-B irradiation. Mice were killed at selected times after irradiation. The level of dimers in the epidermal p53 gene was measured using the T4 endonuclease V assay with quantitative Southern hybridization. Topical alpha-tocopherol caused a 55% reduction in the formation of cyclobutane pyrimidine dimers in the epidermal p53 gene. The rate of reduction of pyrimidine dimers between 1 and 10 hours after irradiation was similar in UV-irradiated mice, regardless of alpha-tocopherol treatment. Therefore, the lower level of cyclobutane pyrimidine dimers in UV-irradiated mice treated with alpha-tocopherol than in control UV-irradiated mice resulted from the prevention of formation of the dimers, and not from enhanced repair of these lesions. Our results indicate that alpha-tocopherol acts as an effective sunscreen in vivo, preventing the formation of premutagenic DNA lesions in a gene known to be important in skin carcinogenesis

Mammary tumorigenesis in APC{sup min/+} mice is enhanced by X-irradiation with a characteristic age dependence

Energy Technology Data Exchange (ETDEWEB)

Tatsuhiko, Imaoka; Mayumi, Nishimura; Shizuko, Kakinuma; Yoshiya, Shimada [National Institute of Radiological Sciences, Experimental Radiobiology for Children' s Health Research Group, Research, Center for Radiation Protection (Japan); Mieko, Okamoto [Tokyo Metropolitan Institute of Medical Science (Japan)

2006-07-01

The ApcM{sup min/+} (Min) mouse is a genetically predisposed model of both intestinal and mammary tumorigenesis. We investigated age-related changes in the susceptibility of mice (before, during and after puberty) to radiation-induced mammary tumorigenesis using this model. Female Min and wild-type mice having the C57BL/6J background were irradiated with 2 Gy of X-rays at 2, 5, 7 and 10 weeks and sacrificed at 18 weeks of age. Min mice irradiated at 7 to 10 weeks of age (after puberty) developed mammary tumors with squamous metaplasia, whereas their wild-type litter-mates did not. Interestingly, irradiation of Min mice at 2 to 5 weeks (before and during puberty, respectively) did not induce mammary tumors but rather cystic nodules with metaplasia. The mammary tumors exhibited increased nuclear beta-catenin protein and loss of the wild-type Apc allele. Our results show that susceptibility to radiation-induced mammary tumorigenesis increases after puberty in Min mice, suggesting that the tumorigenic effect of ionizing radiation targets the lobular-alveolar progenitor cells, which increase in number with age and are controlled by beta-catenin signaling. (author)

Experimental studies on anti-oxidants reducing lipid peroxidation of irradiated mice

International Nuclear Information System (INIS)

Du Zeji; Liu Keliang; Su Liaoyuan

1993-08-01

The free radical plays an important role in the irradiation damage. The irradiation damage would be reduced if anti-oxidants is used, because anti-oxidants can scavenge free radicals and suppress lipid peroxidation. In the study, a fluoro-spectrophotometer was used to determine the changes of MDA levels in mice tissues and serum after irradiation and the protective effect of anti-oxidants of Vit E and DMSO on damage caused by free radicals. The results are as follows: (1) The highest MDA level was at 12 to 24 hours after irradiation dose of 3.0 Gy. (2) The MDA level is increasing with the increasing of irradiation dose. It means the MDA level can indicate the extent of irradiation damage. (3) Both Vit E and DMSO had a powerful effect on reducing MDA level, but the effect of DMSO was stronger than Vit E. The optimum doses of them were 0.25 mg/g body weight and 10 mg/g body weight respectively. (4) The best effect obtained was to use Vit E and DMSO simultaneously

Safety of dried sambiloto Andrographis paniculata (Burm. F.) nees gamma irradiated based on acute toxicity aspect in mice swiss webster

International Nuclear Information System (INIS)

Ermin Katrin; Susanto; Hendig Winarno

2014-01-01

Andrographis paniculata nees (Family: Acanthaceae) is a medicinal plant commonly cultivated in Asian countries. The purpose of this study was to evaluate the safety of gamma irradiated sambiloto against to animal test (mice) and to support the application of nuclear techniques for radiation pasteurization of sambiloto as health products without changing the properties. In the acute toxicity test was observed the effects of the tested material on behavioral changes, abnormalities in the function of several organs and body weight changes in animal test every day for 2 weeks. The results showed that the ethanol extract of unirradiated and irradiated with dose of 7.5 kGy) sambiloto were not toxic to mice. Lethal Dose 50 (DL 50 ) of ethanol extract from sambiloto unirradiated or irradiated at the dose of 7.5 kGy was > 5000 mg/kg BW. At the highest dose tested 5000 mg/kg BW mice there were no significant toxic effects and no mice that died during the experiment, therefore ethanol extracts of un irradiated and irradiated samples could be declared safe. (author)

Transplantation of bone marrow cells into lethally irradiated mice

International Nuclear Information System (INIS)

Viktora, L.; Hermanova, E.

1978-01-01

Morphological changes were studied of megakaryocytes in the bone marrow and spleen of lethally irradiated mice (0.2 C/kg) after transplantation of living bone marrow cells. It was observed that functional trombopoietic megakaryocytes occur from day 15 after transplantation and that functional active megakaryocytes predominate in bone marrow and spleen from day 20. In addition, other types of cells, primarily granulocytes, were detected in some megakaryocytes. (author)

Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

Science.gov (United States)

Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

2005-04-01

Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

Effect of ATM heterozygosity on heritable DNA damage in mice following paternal F0 germline irradiation

International Nuclear Information System (INIS)

Baulch, Janet E.; Li, M.-W.; Raabe, Otto G.

2007-01-01

The ataxia telangiectasia mutated (ATM) gene product maintains genome integrity and initiates cellular DNA repair pathways following exposures to genotoxic agents. ATM also plays a significant role in meiotic recombination during spermatogenesis. Fertilization with sperm carrying damaged DNA could lead to adverse effects in offspring including developmental defects or increased cancer susceptibility. Currently, there is little information regarding the effect of ATM heterozygosity on germline DNA repair and heritable effects of paternal germline-ionizing irradiation. We used neutral pH comet assays to evaluate spermatozoa 45 days after acute whole-body irradiation of male mice (0.1 Gy, attenuated 137 Cs γ rays) to determine the effect of ATM heterozygosity on delayed DNA damage effects of Type A/B spermatogonial irradiation. Using the neutral pH sperm comet assay, significant irradiation-related differences were found in comet tail length, percent tail DNA and tail extent moment, but there were no observed differences in effect between wild-type and ATM +/- mice. However, evaluation of spermatozoa from third generation descendants of irradiated male mice for heritable chromatin effects revealed significant differences in DNA electrophoretic mobility in the F 3 descendants that were based upon the irradiated F 0 sire's genotype. In this study, radiation-induced chromatin alterations to Type A/B spermatogonia, detected in mature sperm 45 days post-irradiation, led to chromatin effects in mature sperm three generations later. The early cellular response to and repair of DNA damage is critical and appears to be affected by ATM zygosity. Our results indicate that there is potential for heritable genetic or epigenetic changes following Type A/B spermatogonial irradiation and that ATM heterozygosity increases this effect

Phenotypic characterization of thymic prelymphoma cells of B10 mice treated with split-dose irradiation

International Nuclear Information System (INIS)

Muto, M.; Kubo, E.; Kamisaku, H.; Sado, T.

1990-01-01

Using an intrathymic injection assay on B10 Thy-1 congenic mice, it was demonstrated that thymic prelymphoma cells first developed within the thymuses from 4 to 8 days after split-dose irradiation and were detected in more than 63% of the test donor thymuses when examined at 21 and 31 days after irradiation. Moreover, some mice (25%) at 2 mo after split-dose irradiation had already developed thymic lymphomas in their thymuses. To characterize these thymic prelymphoma cells, the thymocytes from B10 Thy-1.1 mice 1 mo after irradiation were stained with anti-CD4 and anti-CD8 mAb and were sorted into four subpopulations. These fractionated cells were injected into the recipient thymuses to examine which subpopulation contained thymic prelymphoma cells. The results indicated that thymic prelymphoma cells existed mainly in CD4- CD8- and CD4- CD8+ thymocyte subpopulations and also in CD4+ CD8+ subpopulation. T cell lymphomas derived from CD4- CD8- prelymphoma cells had mainly CD4- CD8- or CD4- CD8+ phenotypes. T cell lymphomas developed from CD4- CD8+ prelymphoma cells mainly expressed CD4- CD8+ or CD4+ CD8+ phenotype. T cell lymphomas originating from CD4+ CD8+ prelymphoma cells were mainly CD4+ CD8+ but some CD4- CD8+ or CD4+ CD8- cells were also present. These thymic prelymphoma cells were further characterized phenotypically in relation to their expression of the marker defined by the mAb against J11d marker and TL-2 (thymus-leukemia) Ag, which is not expressed on normal thymocytes of B10.Thy-1.2 or B10.Thy-1.1 strain, but appears on the thymocytes of lymphomagenic irradiated mice. The results indicated that the prelymphoma cells existed in J11d+, TL-2+ cells

Protective effect of Hippophae rhamnoides leaf extract on gamma irradiation induced clastogenecity in mice

International Nuclear Information System (INIS)

Tyagi, Anuradha; Prasad, Jagdish; Bala, Madhu

2012-01-01

Hippophae rhamnoides (sea buckthorn) is a plant belonging to Elaeagnaceae family and is distributed worldwide. It has variety of uses from nutritional food to pharmacological application. The study was aimed to analyse the extract from Hippophae rhamnoides leaves for their possible protective effects against the whole body 60 Co-a-irradiation. The study was performed on six groups of male mice i.e. untreated group, H. rhamnoides extract group, irradiated (2Gy), irradiated (3Gy), H. rhamnoides and irradiated (2Gy) and H. rhamnoides and irradiated (3Gy). In each group micronucleus test was performed utilising bone marrow and peripheral blood. The mice were sacrificed 30 hrs after treatment and analysed for the presence of micronuclei. In the present study, there was no significant increase in the frequency of either micronucleated polychromatic erythrocytes (MNPCEs) or normochromatic erythrocytes (NCE) in H. rhamnoides extract treated group over the negative control group of animals, indicating its non-clastogenic and non-toxic activity in the erythropoietic system. H. rhamnoides extract showed good anti-clastogenic activity against the a-irradiation induced clastogenecity in both the tissues i.e. bone marrow and peripheral blood by reducing the frequency of micronuclei. Also the administration of H. rhamnoides extract along with irradiation was slightly able to increase the frequency of PCE in bone marrow as well as in peripheral blood in comparison to the irradiated group (2Gy and 3Gy) indicating its ability to reduce the toxicity caused by irradiation in the erythropoietic system. Thus the results indicate the non-clastogenic effect of H. rhamnoides leaf extract and significant protective activity against 60 Co-a-irradiation suggesting its pharmacological significance for development of radioprotector. (author)

Lack of effect on the chromosomal non-disjunction in aged female mice after low dose x-irradiation

Energy Technology Data Exchange (ETDEWEB)

Strausmanis, R; Hendrikson, I B; Holmberg, M; Roennbaeck, C [Research Inst. of National Defence, Sundbyberg (Sweden). Dept. 4

1978-02-01

Karyotypes were determined in 1064 embryos of aged C57/BL mothers. The virgin female mice were irradiated with 0, 4, 8 or 16 R of X-rays, respectively, and placed with young untreated males 5 days after irradiation. 10.5-days old embryos were recovered from the uterus. Aneuploid embryos classified as alive (heart beats observed at the dissection) were 1 monosomic in the control group (496 embryos) and 2 trisomics in the irradiated group (568 embryos). The number of aneuploid embryos classified as dead was 4 trisomic cases in the control group and 3 trisomics in the irradiated group. The data indicate that trisomic embryos are not uncommon in the mouse but are eliminated in post-implantation death. In contrast to the results of Yamamoto et al. the present data do not demonstrate an increased frequency of chromosome abnormalities in embryos of aged mice X-irradiated before mating as compared to non-irradiated ones.

Lack of effect on the chromosomal non-disjunction in aged female mice after low dose x-irradiation

International Nuclear Information System (INIS)

Strausmanis, R.; Hendrikson, I.-B.; Holmberg, M.; Roennbaeck, C.

1978-01-01

Karyotypes were determined in 1064 embryos of aged C57/BL mothers. The virgin female mice were irradiated with 0, 4, 8 or 16 R of X-rays, respectively, and placed with young untreated males 5 days after irradiation. 10.5-days old embryos were recovered from the uterus. Aneuploid embryos classified as alive (heart beats observed at the dissection) were 1 monosomic in the control group (496 embryos) and 2 trisomics in the irradiated group (568 embryos). The number of aneuploid embryos classified as dead was 4 trisomic cases in the control group and 3 trisomics in the irradiated group. The data indicate that trisomic embryos are not uncommon in the mouse but are eliminated in post-implantation death. In contrast to the results of Yamamoto et al. the present data do not demonstrate an increased frequency of chromosome abnormalities in embryos of aged mice X-irradiated before mating as compared to non-irradiated ones

Studies in mice fed a diet containing irradiated fish

International Nuclear Information System (INIS)

1979-01-01

Three groups of mice were observed in utero and for eighty (80) weeks thereafter to study growth, food consumption, hematology, blood chemistry and survival with particular interest in carcinogenic potential. Group I received only Purina Mouse Chow, Group II received a diet composed of 45% non-irradiated fish and 55% Purina Mouse Chow, and Group III received a diet composed of 45% gamma irradiated fish and 55% Purina Mouse Chow. Differences observed in body weights between control and fish treated diets were due to the incorporation of fish into the diet and not the results of fish being treated with gamma irradiation. Differences observed in food consumption between control and fish treated diets were due to the incorporation of fish into the diet and not the result of fish being treated with gamma irradiation. No daily observations were made which could be attributed to the treatment of fish with gamma irradiation. No observations were made at any time interval for hematology which could be attributed to the treatment of fish with gamma irradiation. No observations were made at any time interval for clinical chemistry which could be attributed to the treatment of fish with gamma irradiation. Palpable mass data did not reveal any trends which could be related to the treatment of fish with gamma irradiation. Gross observations at necropsy were limited to spontaneously occurring lesions or artifacts of necropsy technique commonly associated with animals of this species and age. Organ weight data did not reveal any trends which could be related to the treatment of fish with gamma irradiation. Pathological findings were limited to spontaneously occurring lesions or artifacts of necropsy technique commonly associated with animals of this species and age. (orig.)

Sesamol attenuates cytogenetic damages in bone marrow cells of whole body gamma irradiated mice

International Nuclear Information System (INIS)

Kumar, Arun; Tamizh Selvan, G.; Adhikari, Jawahar S.; Chaudhury, N.K.

2014-01-01

Whole body radiation exposure cause damages to all vital organs and bone marrow is the most sensitive. Pre-treatment with antioxidant as single prophylactic dose is expected to lower induction of damages in bone marrow. In the present study we have focused on sesamol, a dietary antioxidant mediated radioprotection in bone marrow cells of gamma irradiated mice and compared with melatonin. Male C57BL/6 mice were intraperitoneally administered with sesamol (10 and 20 mg/kg body) and after 30 minutes exposed to whole body gamma radiation using 60 Co Teletherapy unit. Mice were injected with 0.2 ml of a metaphase arresting agent (0.05% colchicine) intra-peritoneally 3 hours prior to sacrifice (24 hrs. post-irradiation). Bone marrow cells were flushed out from femurs of each animal and processed for chromosomal aberration assay. Another set of experiment without colchicine injection was performed to access the DNA damage in bone marrow using alkaline comet assay. At least 100 metaphases per animal were scored under light microscope to record various aberrations and total chromosomal aberrations (TCA) was calculated. Similar measurements were performed with melatonin for comparing the efficacy of sesamol. Gamma irradiation has increased the chromatid type aberrations (break formation, fragment) and chromosomal type aberrations (ring formation, acentric) in bone marrow cells. The results have shown significant (p< 0.001) increase in TCA of irradiated mice than control. While pre-treatment of sesamol and melatonin 10 mg/kg significantly (p<0.05) reduced the TCA. The extend of protection has increased at 20 mg/kg significantly (p<0.001) as evident from the reduced TCA compared to irradiated group. Interestingly, sesamol and melatonin have shown similar extent of reduction of TCA. Thus sesamol has demonstrated strong ability to protect bone marrow at low dosage. These investigations on sesamol mediated protection in bone marrow are likely to benefit development of

Influence of vaccination with Bordetella pertussis cells on haemopoiesis in sublethally irradiated mice and their radiation lethality

International Nuclear Information System (INIS)

Kwiek, S.; Bitny-Szlachto, S.

1978-01-01

Post-irradiation lethality of CFW mice has turned out to be enhanced by vaccination with Bordetella pertussis cells 10 min., 48 hrs. prior or 48 hrs. after the exposure to X-rays. The sensitization factor was found to be 1.23, as it revealed by decrease of radiation LD 50 . Granulopoiesis and erythropoiesis proved to be stimulated by vaccination, in mice irradiated with 200 or 400 R but not in those after 600 R. Direct radiosensitivity of CFU was not altered by vaccination, but the subsequent loss of bone marrow stem cells was enhanced in vaccinated mice. On the other hand, endocolonization of spleens with bone marrow stem cells has turned out to be highly enhanced by the vaccine, resulting in confluent growth of colonies. This effect of the vaccine was not abolished by hydroxyurea given 15 min. or 1 hr. after vaccination. Enhanced post-irradiation lethality is considered to result from fall of the bone marrow stem cell pool below the level indispensable to ensure the post-irradiation recovery of the haemopoietic system. (author)

Effect of prolonged irradiation by low dose-rate ionizing radiation on the hemopoiesis of mice

Energy Technology Data Exchange (ETDEWEB)

Yanai, Takanori; Shirata, Katsutoshi; Saitou, Mikio; Tanaka, Satoshi; Onodera, Junichi; Otsu, Hiroshi; Sato, Fumiaki [Institute for Environmental Sciences, Department of Radiobiology, Rokkasho, Aomori (Japan)

1999-07-01

To evaluate effects of prolonged irradiation by low dose-rate ionizing radiation on the hemopoiesis of mice, SPF C3H/HeN female mice were irradiated by {sup 137}Cs {gamma}-rays with doses of 1-8 Gy at the dose rate of 20 mGy (22 h-day){sup -1}. After irradiation, the number of hemopoietic cells contained in bone marrow was determined by the methods of CFU-S and CFU-GM assay, and the number of peripheral blood cells was counted. It was shown that the day 12-CFU-S, which is in the earlier stage of differentiation, decreased as the dose increased. Decreases of the numbers of day 7-CFU-S and CFU-GM were also observed. However, there were no remarkable changes in the number of peripheral blood cells. (author)

Comparative study of the reciprocal translocation rate in spermatocytes after irradiation of newborn and adult mice

International Nuclear Information System (INIS)

Pomerantseva, M.D.

1978-01-01

The yield of reciprocal translocations was investigated in spermatocytes of the CBA male mice irradiated immediately after their brith or after the irradiation of the stem spermatogonia at the age of 3 months. The irradiation doses were 100, 200, 400 R X-rays 300 R gamma-rays 60 Co. The yield of translocations in both groups was the same

Late vascular effects in irradiated mice brain. In relation to experimental radionecrosis

Energy Technology Data Exchange (ETDEWEB)

Yoshii, Y; Maki, Y [Tsukuba Univ., Sakura, Ibaraki (Japan); Phillips, T L

1982-03-01

The whole brains of mice were irradiated with 250 kVp X-ray at 120 rad min/sup -1/ (1.6 mm Cu HVL, TSD 50 cm) and a histological study was done. The dose range of X-irradiation was from 1300 to 2500 rads. i.e., 1300, 1500, 1750, 2000, and 2500 rads. In the microscopic examination, the mice were killed at the regular postirradiation intervals of between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. A histological examination was performed by a morphometric estimation of vascular lesion in which the degree of the damage to the arterial system was scored through whole serial brain sections. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectatic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large artery were observed. Incidence of the fibrinoid necrosis increased dose dependently between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 - 87 weeks and can be used to quantify the vessel injury and a fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis.

Effect of antibiotics and bifidobacterial preparations on the intestinal microflora in mice irradiated with gamma quanta

International Nuclear Information System (INIS)

Korshunov, V.M.; Pinegin, B.V.; Mal'tsev, V.N.; Kissina, E.V.; Ikonnikova, T.B.; Goncharova, G.I.; Lyannaya, A.I.; Institut Biofiziki, Moscow; Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Ehpidemiologii i Mikrobiologii)

1980-01-01

Mice weighing 19-20 g have been exposed to the dose of 700 R and devided into 3 groups. During the first five days animals of the first group received antibiotics perorally - 40 units phenoxypenicillin, 30 units oxytetracycline, 40 units streptomicine. On the 6th, 10th and 15th days after irradiation the bifidobacterium preparation (75-41 strain) has been introduced perorally in the amount of 5x10 8 cells. Animals of the second group have received antibiotics alone in the same period as mice of the first group but the sterile physiological solution has been introduced instead of bifidobacteria. The sterile physiological solution has been perorally introduced to animals of the third group instead of antibiotics and bifidobacteria. The complex treatment has lead to the increase of survival percentage as compared with animals which have not been treated. The normalization of the intestines microbic landscape is observed in irradiated mice, subjected to treatment with antibiotics and bifidobacteria. It is expressed in a considerable reduction in the amount of clostridium, enterococci, intestinal bacilli and proteus as compared with the amount of these microbes in the intestines of non-treated mice. At the same time, a certain increase of lactobacilli amount to the level characteristic of lactobacilli in the intestinal tract of non-treated animals is observed in the intestines of irradiated and treated mice

Effect of antibiotics and bifidobacterial preparations on the intestinal microflora in mice irradiated with gamma quanta

Energy Technology Data Exchange (ETDEWEB)

Korshunov, V M; Pinegin, B V; Mal' tsev, V N; Kissina, E V; Ikonnikova, T B; Goncharova, G I; Lyannaya, A I [Vtoroj Moskovskij Gosudarstvennyj Meditsinskij Inst. (USSR); Institut Biofiziki, Moscow (USSR); Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Ehpidemiologii i Mikrobiologii)

1980-07-01

Mice weighing 19-20 g have been exposed to the dose of 700 R and devided into 3 groups. During the first five days animals of the first group received antibiotics perorally - 40 units phenoxypenicillin, 30 units oxytetracycline, 40 units streptomicine. On the 6th, 10th and 15th days after irradiation the bifidobacterium preparation (75-41 strain) has been introduced perorally in the amount of 5x10/sup 8/ cells. Animals of the second group have received antibiotics alone in the same period as mice of the first group but the sterile physiological solution has been introduced instead of bifidobacteria. The sterile physiological solution has been perorally introduced to animals of the third group instead of antibiotics and bifidobacteria. The complex treatment has lead to the increase of survival percentage as compared with animals which have not been treated. The normalization of the intestines microbic landscape is observed in irradiated mice, subjected to treatment with antibiotics and bifidobacteria. It is expressed in a considerable reduction in the amount of clostridium, enterococci, intestinal bacilli and proteus as compared with the amount of these microbes in the intestines of non-treated mice. At the same time, a certain increase of lactobacilli amount to the level characteristic of lactobacilli in the intestinal tract of non-treated animals is observed in the intestines of irradiated and treated mice.

Life span, testis damage and immune cell populations of spleen in C57BL mice with neutron irradiation by lying flat pose

Energy Technology Data Exchange (ETDEWEB)

Chun, Ki Jung; kim, Myung Sup; Kyung, Yoo Bo [KAERI, Taejon (Korea)

2003-10-01

This study deals with the biological effects of black mouse (C57BL) irradiated with neutron irradiation by using Boron Neutron Capture Therapy facility in HANARO reactor. These include mortality, body wt., hair color, testis volume, sperm count and immune cell populations in mouse spleen after 80 days later by thermal neutron irradiation. Six week old C57BL male mice were irradiated with neutron irradiation for 1 hr or 2 hrs (flux : 1.036739E +09). These irradiat ion doses estimated 15Gy and 30Gy, respectively. Survival days and hair color in mice was checked. On day 80 after irradiation, testis were taken for volume and sperm count. Also spleen was taken for FACS and spleen cells were isolatd and discarded RBC by treating with lysising solution. These cells were placed on ice and immunofluorescence staining was performed. Phycoerythrin (PE )-anti-CD3e, fluorescein isothiocyanate (FITC)-anti-CD4, and FITC-anti-CD8 were added, then the immunostaining cells were incubated on ice for 40 min. The resulting cells were washed with a PBS buffer 3 times and analyzed using a Flow cytometer. All experimental animals survived over 90 days but in case of 30 Gy neutron irradiation, black mice hair were changed white color on the center of the back. Neutron irradiation of black mice show similar in damage of spleen immune cells by subpopulation of T helper and T cytotoxic cells compared to the control non - irradiated group. These results show that treatment of neutron irradiation without boron compounds for 2 hrs in mice can survive over 90 days with hair color change from black to white. Damaged spleen cells recover after long time by irradiation but testis volume and no. of sperm are not recover compared to the normal group in response to neutron irradiation.

Life span, testis damage and immune cell populations of spleen in C57BL mice with neutron irradiation by lying flat pose

International Nuclear Information System (INIS)

Chun, Ki Jung; kim, Myung Sup; Kyung, Yoo Bo

2003-01-01

This study deals with the biological effects of black mouse (C57BL) irradiated with neutron irradiation by using Boron Neutron Capture Therapy facility in HANARO reactor. These include mortality, body wt., hair color, testis volume, sperm count and immune cell populations in mouse spleen after 80 days later by thermal neutron irradiation. Six week old C57BL male mice were irradiated with neutron irradiation for 1 hr or 2 hrs (flux : 1.036739E +09). These irradiat ion doses estimated 15Gy and 30Gy, respectively. Survival days and hair color in mice was checked. On day 80 after irradiation, testis were taken for volume and sperm count. Also spleen was taken for FACS and spleen cells were isolatd and discarded RBC by treating with lysising solution. These cells were placed on ice and immunofluorescence staining was performed. Phycoerythrin (PE )-anti-CD3e, fluorescein isothiocyanate (FITC)-anti-CD4, and FITC-anti-CD8 were added, then the immunostaining cells were incubated on ice for 40 min. The resulting cells were washed with a PBS buffer 3 times and analyzed using a Flow cytometer. All experimental animals survived over 90 days but in case of 30 Gy neutron irradiation, black mice hair were changed white color on the center of the back. Neutron irradiation of black mice show similar in damage of spleen immune cells by subpopulation of T helper and T cytotoxic cells compared to the control non - irradiated group. These results show that treatment of neutron irradiation without boron compounds for 2 hrs in mice can survive over 90 days with hair color change from black to white. Damaged spleen cells recover after long time by irradiation but testis volume and no. of sperm are not recover compared to the normal group in response to neutron irradiation

Revising the Radiobiological Model of Synchronous Chemotherapy in Head-and-Neck Cancer: A New Analysis Examining Reduced Weighting of Accelerated Repopulation

Energy Technology Data Exchange (ETDEWEB)

Meade, Sara, E-mail: sara.meade@uhb.nhs.uk [Hall-Edwards Radiotherapy Research Group, Cancer Centre, Queen Elizabeth Hospital, Birmingham (United Kingdom); Sanghera, Paul [Hall-Edwards Radiotherapy Research Group, Cancer Centre, Queen Elizabeth Hospital, Birmingham (United Kingdom); McConkey, Christopher [Clinical Trials Unit, Warwick Medical School, University of Warwick, Warwick (United Kingdom); Fowler, Jack [Departments of Human Oncology and Medical Physics, University of Wisconsin, Madison, Wisconsin (United States); Fountzilas, George [AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki (Greece); Glaholm, John; Hartley, Andrew [Hall-Edwards Radiotherapy Research Group, Cancer Centre, Queen Elizabeth Hospital, Birmingham (United Kingdom)

2013-05-01

Purpose: Previous studies of synchronous chemoradiation therapy have modeled the additional effect of chemotherapy as additional radiation therapy biologically effective dose (BED). Recent trials of accelerated versus conventional fractionation chemoradiation have cast doubt on such modeling. The purpose of this study was to identify alternative models. Methods and Materials: Nine trials of platinum-based chemoradiation were identified. In radiation therapy-alone arms, the radiation therapy BED for tumor was calculated using standard parameters. In chemoradiation arms, 3 methods were used to calculate tumor BED (tBED): additional BED, addition of 9.3 Gy BED for tumor to the radiation therapy BED; zero repopulation, BED with no correction for repopulation; variable t{sub p} (the average doubling time during accelerated repopulation), values of t{sub p} 3-10 were used to examine a partial suppression of repopulation. The correlations between the calculated percentage change in tBED for each method and observed percentage change in local control were assessed using the Pearson product moment correlation. Results: Significant correlations were obtained for all 3 methods but were stronger with zero repopulation (P=.0002) and variable t{sub p} (t{sub p} = 10) (P=.0005) than additional BED (P=.02). Conclusions: Radiobiological models using modified parameters for accelerated repopulation seem to correlate strongly with outcome in chemoradiation studies. The variable t{sub p} method shows strong correlation for outcome in local control and is potentially a more suitable model in the chemoradiation setting. However, a lack of trials with an overall treatment time of more than 46 days inhibits further differentiation of the optimal model.

Unscheduled DNA synthesis and elimination of DNA damage in liver cells of. gamma. -irradiated senescent mice

Energy Technology Data Exchange (ETDEWEB)

Gaziev, A.I.; Malakhova, L.V. (AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki)

1982-10-01

The level of 'spontaneous' and ..gamma..-radiation-induced DNA synthesis which is not inhibited with hydroxyurea (unscheduled synthesis) is considerably lower in hepatocytes of 18-22-month-old mice than that of 1.5-2-month-old mice. The dose-dependent increase (10-300 Gy) of unscheduled DNA synthesis (UDS) in hepatocytes of senescent mice is higher than in young animals. The elimination of damage in DNA of ..gamma..-irradiated hepatocytes (100 Gy) was examined by using an enzyme system (M. luteus extract and DNA-polymerase I of E. coli). It was found that the rate of elimination of the DNA damage in hepatocytes of 20-month-old mice is lower than that of 2-month-old mice although the activities of DNA-polymerase ..beta.. and apurinic endonuclease remain equal in the liver of both senescent and young mice. However, the nucleoids from ..gamma..-irradiated liver nuclei of 2-month-old mice are relaxed to a greater extent (as judged by the criterion of ethidium-binding capacity) than those of 20-month-old mice. The results suggest that there are limitations in the functioning of repair enzymes and in their access to damaged DNA sites in the chromatin of senescent mouse liver cells.

Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice.

Science.gov (United States)

Raber, Jacob; Torres, Eileen Ruth S; Akinyeke, Tunde; Lee, Joanne; Weber Boutros, Sydney J; Turker, Mitchell S; Kronenberg, Amy

2018-04-20

The space radiation environment includes helium (⁴He) ions that may impact brain function. As little is known about the effects of exposures to ⁴He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation with ⁴He ions (250 MeV/n; linear energy transfer (LET) = 1.6 keV/μm; 0, 21, 42 or 168 cGy). Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. ⁴He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2) in the cortex. There was an effect of radiation on apolipoprotein E (apoE) levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued fear

Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice

Directory of Open Access Journals (Sweden)

Jacob Raber

2018-04-01

Full Text Available The space radiation environment includes helium (4He ions that may impact brain function. As little is known about the effects of exposures to 4He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1 mice three months following irradiation with 4He ions (250 MeV/n; linear energy transfer (LET = 1.6 keV/μm; 0, 21, 42 or 168 cGy. Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. 4He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2 in the cortex. There was an effect of radiation on apolipoprotein E (apoE levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued

Uptake of carbon monoxide by C3H mice following X irradiation of lung only or total-body irradiation with 60Co

International Nuclear Information System (INIS)

Rappaport, D.S.; Niewoehner, D.E.; Kim, T.H.; Song, C.W.; Levitt, S.H.

1983-01-01

Carbon monoxide uptake (V/sub co/) and ventilation rate (VR) of C3H mice were determined at 14 weeks following either X irradiation of lungs only or total-body irradiation with 60 Co at different dose rates. Following localized X irradiation of lung at 97 /sub c/Gy/min there was a reduction in V/sub co/, which was inversely related to radiation dose, with a small reduction below control levels being detected at 7 Gy, the lowest dose tested. An increase in VR could be detected only at doses of 11 Gy, or more. Another group of animals received 11.5 Gy total-body irradiation at either 26.2 or 4.85 /sub c/Gy/min fllowed by transplantation with syngeneic bone marrow. Following total-body irradiation, V/sub co/ was significantly reduced by about 37% at the higher dose rate and 23% at the lower dose rate. In contrast, a trend toward elevated VR was detected only at the higher dose rate.The results indicate that V/sub co/ is a sensitive indicator of radiation-induced lung injury and that under the experimental conditions used V/sub co/ is a more sensitive indicator of radiation-induced lung injury in C3H mice than VR

X-irradiation of mice in the early fetal period. Pt. 2

International Nuclear Information System (INIS)

Kriegel, H.; Weber, L.; Schmahl, W.

1979-01-01

Pregnant NMRI mice were X-irradiated with 50, 100 and 200 R, respectively, on the twelfth gestational day. The brains of their offspring were weighed and examined for acetylcholinesterase and Na,K-ATPase activities from birth until the 64th postnatal day. The postnatal brain weights were influenced by the prenatal irradiation in a dose-dependent manner. At birth the brains of the treated animals weighed less than those of the controls. After a limited period of restitution (postnatal days 3 to 10), weights fell again, as compared to the controls, and persisted at subnormal levels. This was assumed to be a sequel of surplus neuron cell formation and their speedy degradation as soon as neuronal function had been established. The curves of the activites (per gram of brain tissue) of acetylcholinesterase as well as Na,K-ATPase showed oscillating compensatory responses to the prenatal irradiation. Activities were preferentially found at supernormal levels, the oscillation lasting as long as the restitution period of the brain weights. With the 50 R and 100 R groups, enzyme activities were steadily above the control levels from the 16th until the 48th day after birth. On the 64th postnatal day all enzyme activities but one (200 R, Na,K-ATPase) had returned to the control levels. Oscillating responses to prenatal X-irradiation have been described for the DNA-synthesis in livers and brains of mice during the first three postnatal weeks. From this perspective, our results are discussed as the outcome of radiation-induced alterations in genome activity. (orig.) [de

Chromosome aberrations in F1 from irradiated male mice studied by their synaptonemal complexes

International Nuclear Information System (INIS)

Kalikinskaya, E.I.; Kolomiets, O.L.; Shevchenko, V.A.; Bogdanov, Yu.F.

1986-01-01

Possible implications of surface-spread synaptonemal complex (SC) karyotyping in analysing the causes of sterility of F 1 from irradiated male mice are demonstrated in this work. After irradiation by 137 Cs γ-rays at a dose of 5 Gy the males were mated to unirradiated females and genetic analysis of fertility in the F 1 progeny was carried out. Males with abnormal fertility were examined for the presence of chromosome aberrations in diakinesis-metaphase I and in pachytene by the method of surface-spread SC karyotyping. In most cases, SC karyotyping provides additional information and permits the detection and analysis of aberrations that are not revealed in diakinesis. Two reciprocal translocations, one X autosomal and one nonreciprocal translocation were discovered in five F 1 males studied. It is concluded that the method is efficient in detecting translocations in pachytene in partially fertile F 1 hybrids of irradiated and normal mice. (orig.)

Genistein Protects Against Biomarkers of Delayed Lung Sequelae in Mice Surviving High-Dose Total Body Irradiation

Science.gov (United States)

DAY, Regina M.; BARSHISHAT-KUPPER, Michal; MOG, Steven R.; MCCART, Elizabeth A.; PRASANNA, P. G. S.; DAVIS, Thomas A.; LANDAUER, Michael R.

2008-01-01

The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60Co, 0.6 Gy/min). Experimental groups were: No treatment + Sham (NC), Vehicle + Sham (VC), Genistein + Sham (GC), Radiation only (NR), Vehicle + Radiation (VR), Genistein + Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13–28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. PMID:18434686

Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation

International Nuclear Information System (INIS)

Day, R.M.; Barshishat-Kupper, M.; Mog, S.R.; Mccart, E.A.; Prasanna, P.G.S.; Landauer, M.R.; Davis, T.A.

2008-01-01

The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60 Co, 0.6 Gy/min). Experimental groups were: No treatment+Sham (NC), Vehicle+Sham (VC), Genistein+Sham (GC), Radiation only (NR), Vehicle+Radiation (VR), Genistein+Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13-28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. (author)

Mechanisms involved in the differential recovery of CD4 and CD8 T-lymphocytes after local irradiation in mice

International Nuclear Information System (INIS)

De Ruysscher, D; Waer, M.; Vandeputte, M.; Van der Schueren, E.

1990-01-01

The mechanisms involved in the differential recovery of CD4 (helper/inducer phenotype) and CD8 (Cytotoxic/suppressor phenotype) T-lymphocytes after fractionated local irradiation were investigated. In mice, a better recovery of CD4 cells than of CD8 cells was found, while the reverse has been described in humans. Differences in radiosensivitity between CD4 and CD8 mouse splenocytes could not be found. No sequestration of CD8 cells in irradiated tissues could be demonstrated. Irradiation of the thymus did not influence the observed immune changes. Altered thymic production of CD4 and CD8 cells could be excluded by intrathymic injection of FITC (fluorescein isothiocyanate). Hindlimb and tail irradiation did suggest that the differential recovery of CD4 and CD8 T-lymphocytes after local irradiation is determined by extrathymic factors in man and mice, and that the observed differences in immune recovery between man and mice are due to defective thymic function in the former and normal function in the latter. (author). 12 refs.; 5 figs.; 2 tabs

Hematologic status of mice submitted to sublethal total body irradiation with mixed neutron-gamma radiation

International Nuclear Information System (INIS)

Herodin, F.; Court, L.

1989-01-01

The hematologic status of mice exposed to sublethal whole body irradiation with mixed neutron-gamma radiation (mainly neutrons) is studied. A slight decrease of the blood cell count is still observed below 1 Gy. The recovery of bone marrow granulocyte-macrophage progenitors seems to require more time than after pure gamma irradiation [fr

Diabetes susceptibility of BALB/cBOM mice treated with streptozotocin. Inhibition by lethal irradiation and restoration by splenic lymphocytes

International Nuclear Information System (INIS)

Paik, S.G.; Blue, M.L.; Fleischer, N.; Shin, S.

1982-01-01

In genetically susceptible strains of mice, repeated injections of a subdiabetogenic dose of streptozotocin induces the development of progressive insulin-dependent hyperglycemia. We showed previously that host T-cell functions play an obligatory etiologic role in this experimental disease by demonstrating that the athymic nude mouse is resistant to diabetes induction unless its T-cell functions are reconstituted by thymus graft. Here we show that lethal irradiation of euthymic (+/nu) mice of BALB/cBOM background causes selective resistance of the mice to the diabetogenic effects of the multiple low doses of streptozotocin without affecting their sensitivity to a high pharmacologic dose of the toxin. We also show that reconstitution of the irradiated mice with splenic lymphocytes causes the restoration of diabetes susceptibility. Lethally irradiated mice thus represent a useful experimental model for analyzing the host functions involved in the development of this disease. These results provide an additional support for the hypothesis that the induction of diabetes in this model system is mediated by an autoimmune amplification mechanism

Repeated 0.5 Gy gamma-ray irradiation attenuates autoimmune disease in MRL-lpr/lpr mice with up-regulation of regulatory T cells

International Nuclear Information System (INIS)

Mitsutoshi Tsukimoto; Fumitoshi Tago; Hiroko Nakatsukasa; Shuji Kojima

2007-01-01

Complete text of publication follows. MRL-lpr/lpr mice present a single gene mutation on the Fas (CD95) gene that leads to reduced signaling for apoptosis. With aging, these mice spontaneously develop autoimmune disease and are used as a model of systemic lupus erythematosus. We previously reported attenuation of autoimmune disease in MRL-lpr/lpr mice by repeated γ-ray irradiation (0.5 Gy each time). In this study, we investigated the mechanisms of this attenuation focusing the highly activated CD3 + CD4 - CD8 - B220 + T cells, which are characteristically involved in autoimmune pathology in these mice. We measured the weight of the spleen and the population of CD3 + CD4 - CD8 - B220 + T cells. Splenomegaly and increase in percentage of CD3 + CD4 - CD8 - B220 + T cells, which occur with aging in non-irradiated mice, were suppressed in irradiated mice. To investigate the function of CD3 + CD4 - CD8 - B220 + T cells, we isolated these cells from splenocytes by magnetic cell sorting. Isolated CD3 + CD4 - CD8 - B220 + T cells were more resistant to irradiation-induced cell death than isolated CD4 + T cells. Although high proliferation rate and IL-6 production were observed in isolated CD3 + CD4 - CD8 - B220 + T cells, the proliferation rate and IL-6 production were lower in the cells isolated from the irradiated mice. Moreover, the production of autoantibodies (anti-collagen antibody and anti-single strand DNA antibody) was also lowered by irradiation. These results indicate that activation of CD3 + CD4 - CD8 - B220 + T cells and progression of pathology would be suppressed by repeated 0.5 Gy γ-ray irradiation. To uncover the mechanism of the immune suppression, we analyzed population of regulatory T cells (CD4 + CD25 + Foxp3 + ), which suppress activated T cells and excessive autoimmune responses. Intriguingly, significant increase of the percentage of regulatory T cells was observed in irradiated mice. In conclusion, we found that repeated 0.5 Gy γ-ray irradiation

Transplantation of homologous bone marrow cells to lethally irradiated mice: changes in the spleen

Energy Technology Data Exchange (ETDEWEB)

Viktora, L; Hach, P; Zoubkova, M

1975-01-01

Bone marrow cell suspensions were administered intravenously to lethally irradiated mice. The number of colonies in the spleen and the regeneration of hematopoietic tissue in the spleen were studied on the 9th day after irradiation and transplantation. From a comparison of the histological picture and weight of the spleens, the authors conclude that the degree of regeneration of hematopoiesis in the spleen after irradiation and transplantation is reflected in the weight of the spleen as well as in the number of hematopoietic colonies.

High incidence of acute myeloid leukemia in SJL/J mice after X-irradiation and corticosteroids

International Nuclear Information System (INIS)

Resnitzky, P.; Estrov, Z.; Hebrew Univ., Jerusalem; Haran-Ghera, N.

1985-01-01

SJL/J mice which developed a high incidence of spontaneous reticulum cell neoplasms, developed a low rate incidence (20-25%) of myeloid leukemia (ML) after X-irradiation. The possible effect of adrenal steroid imbalance to radiation-induced ML in SJL/J mice was tested. Intact and thymectomized animals were exposed to a single dose of 300 r whole body irradiation and treated with either hydrocortisone acetate, prednisone, metyrapone and adrenocorticotropin as coleukemogenic agents. Hydrocortisone and prednisone exerted a marked coleukemogenic effect, increasing the ML incidence to a similar rate of about 50-70%, at a mean latent period of 300 days. Prominent leukemic infiltration were observed in the bone marrow, spleen, lymph nodes and liver of the leukemic animals. Results of cytological and histological studies, including cytochemistry and ultrastructure, were all consistent with the diagnosis of acute myeloid leukemia (AML). Since AML is the type of human secondary leukemia which appears increasingly in patients treat with alkylating drugs and/or irradiation and corticosteroids for Hodgkin's disease or other neoplastic diseases, the experimental model of AML induced in SJL/J mice could be used for elucidation of mechanisms of leukemogenesis in secondary leukemia. (author)

High incidence of acute myeloid leukemia in SJL/J mice after X-irradiation and corticosteroids

Energy Technology Data Exchange (ETDEWEB)

Resnitzky, P; Estrov, Z; Haran-Ghera, N

1985-01-01

SJL/J mice which developed a high incidence of spontaneous reticulum cell neoplasms, developed a low rate incidence (20-25%) of myeloid leukemia (ML) after X-irradiation. The possible effect of adrenal steroid imbalance to radiation-induced ML in SJL/J mice was tested. Intact and thymectomized animals were exposed to a single dose of 300 r whole body irradiation and treated with either hydrocortisone acetate, prednisone, metyrapone and adrenocorticotropin as coleukemogenic agents. Hydrocortisone and prednisone exerted a marked coleukemogenic effect, increasing the ML incidence to a similar rate of about 50-70%, at a mean latent period of 300 days. Prominent leukemic infiltration were observed in the bone marrow, spleen, lymph nodes and liver of the leukemic animals. Results of cytological and histological studies, including cytochemistry and ultrastructure, were all consistent with the diagnosis of acute myeloid leukemia (AML). Since AML is the type of human secondary leukemia which appears increasingly in patients treat with alkylating drugs and/or irradiation and corticosteroids for Hodgkin's disease or other neoplastic diseases, the experimental model of AML induced in SJL/J mice could be used for elucidation of mechanisms of leukemogenesis in secondary leukemia.

Proliferation studies of the endothelial and smooth muscle cells of the mouse mesentery after irradiation

International Nuclear Information System (INIS)

Hirst, D.G.; Denekamp, J.; Hobson, B.

1980-01-01

A continuous tritium labelling technique was employed to study the effects of external β-radiation on the proliferation of endothelial cells and smooth muscle cells in the mesenteric arterioles of mice. Calculations showed very long turnover times for the two cell populations in control animals (> 2 years for endothelium and > 3 years for smooth muscle). After single doses of 20 and 45 Gy, no significant increase in endothelial proliferation was seen except at 3 weeks. No significant increase in labelling was observed in smooth muscle up to 48 weeks after irradiation. These labelling data have been compared with the pattern of cell depletion of the irradiated endothelium. It was concluded that the depletion was much earlier than expected for a slowly proliferating tissue, if all the cells were cycling very slowly. Such an early depletion is, however, consistent with cell death resulting from a small proportion of the cells having a short cell cycle. The recovery of the endothelial cell numbers between 9 and 12 months was not accompanied by a rise in the fraction of labelled cells. It is suggested that repopulation may occur from outside the treated area. (author)

Premature ageing of pituitary of irradiated ICRC mice

Energy Technology Data Exchange (ETDEWEB)

Pai, S R

1983-11-01

The secretory cycle of pituitary cells has been studied in ICRC young adult mice receiving whole body X-irradiation with the fractionated dose of 150R/wk for 4 wk. Sequential autopsies were performed at 80, 100 and 120 days after the first dose of irradiation. From the tinctorial affinity of the cells it was difficult to classify the pituitary cells under light microscopy. The secretory cytology was therefore studied under electron microscope. It was observed that the growth hormone secreting cells (GH) having well developed Golgi and endoplasmic reticulum (ER) were predominantly spread over the lobe at all three periods. However, the clumping of secretory granules and lytic bodies were seen only in the 120 day group. Few secretary granules, ill-defined Golgi, vesicular cytoplasm and lipid bodies were sequential changes that took place in the follicle-stimulating hormone cells (FSH). Along with these changes in the pituitary, atresia of the ovaries or proliferation of Leydig cells was observed. 3 figures, 16 refs.

The influence of combined treatment of Cd, and γ-irradiation on DNA damage and repair in lymphoid tissues of mice

International Nuclear Information System (INIS)

Privezentsev, K.V.; Sirota, N.P.; Gaziev, A.I.

1996-01-01

The effect of combined treatment of Cd and γ-irradiation on DNA damage and repair was studied in lymphoid tissues of mice using single-cell gel assay. Single i.p. injection of CdCl 2 (1 mg Cd/kg body wt), 2 h prior to irradiation resulted in increasing of DNA lesions in peripheral blood lymphocytes (PBL) when compared to non-injected animals. However, the same treatment, 48 h prior to irradiation is shown to decrease DNA damage in PBL and splenocytes in comparison with untreated mice. In thymocytes maximal protective effect of Cd was determined when mice were irradiated in 24 h after injection. The protective effect observed is due to decreasing of initial level of DNA damage in thymocytes as well as acceleration of DNA repair in PBL and splenocytes. 28 refs.; 2 figs

Inhibitory effects of prior low-dose X-ray irradiation on carbon tetrachloride-induced hepatopathy in acatalasemic mice

International Nuclear Information System (INIS)

Yamaoka, Kiyonori; Kataoka, Takahiro; Taguchi, Takehito; Wang, Da-Hong; Mori, Shuji; Hanamoto, Katsumi; Kira, Shohei; Nomura, Takaharu

2004-01-01

The catalase activities in blood and organs of the acatalasemic (C3H/AnLCs b Cs b ) mouse of C3H strain are lower than those of the normal (C3H/AnLCs a Cs a ) mouse. We examined the effects of prior low-dose (0.5 Gy) X-ray irradiation, which reduced the oxidative damage under carbon tetrachloride-induced hepatopathy in the acatalasemic or normal mice. The acatalasemic mice showed a significantly lower catalase activity and a significantly higher glutathione peroxidase activity compared with those in the normal mice. Moreover, low-dose irradiation increased the catalase activity in the acatalasemic mouse liver to a level similar to that of the normal mouse liver. Pathological examinations and analyses of blood glutamic oxaloacetic and glutamic pyruvic transaminase activity and lipid peroxide levels showed that carbon tetrachloride induced hepatopathy was inhibited by low-dose irradiation. These findings may indicate that the free radical reaction induced by the lack of catalase and the administration of carbon tetrachloride is more properly neutralized by high glutathione peroxidase activity and low-dose irradiation in the acatalasemic mouse liver. (author)

Transcription and activity of antioxidant proteins after ionization irradiation of radiation-resistant and radiation-sensitive mice

International Nuclear Information System (INIS)

Hardmeier, R.

1998-03-01

The involvernent of antioxidant proteins catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH px), and thioredoxin (TRX) in radiobiological processes has been described at the enzyme activity level. We were interested in examining the transcription of these proteins in a mammalian system following ionizing irradiation. In order to answer the question whether radiation effects in sensitive mice (Balb/c) (RS) showed differences at the transcriptional level from radiation effects in resistant mice (C3H) (RR). We exposed the whole body of these strains to X/rays doses of 2, 4, and 6 Gy and sacrificed the animals 5, 15, and 30 minutes after irradiation. The mRNA was isolated from liver and hybrized with probes for antioxidant enzymes and thioredoxin, β-actin was used as a housekeeping gene control. Antioxidant enzyme activities were determined by standard assays. Parameters for aromatic hydroxylation (o-Tyr) and lipid peroxidation (MDA) were determined by HPLC methods. Antioxidant transcription was unchanged in contrast to antioxidant activities. SOD and CAT activities were elevated within 15 minutes in RR animals but not in RS at all radiation doses. Glutathione peroxidase activity was not different between RR and RS mice, and was only moderately elevated after irradiation. No significant differences were found between RR and RS animals at the oxidation level, although a radiation dose-dependent increase of oxidation products was detected in both groups. Quantification of thioredoxin mRNA revealed that RR mice transcribed this protein at a significantly higher level at an earlier time point (5 minutes) than did RS mice. This delay may well be responsible for the radioresistance although no quantitative differences were found. As unchanged transcription of antioxidant enzymes could not have been responsible for the increased antioxidant enzyme activities, preformed antioxidant enzymes may have been released by irradiation. This would be in agreement

Immunization of mice with gamma-irradiated intramuscularly injected schistosomula of Schistosoma mansoni

International Nuclear Information System (INIS)

Bickle, Q.D.; Taylor, M.G.; Doenhoff, M.J.; Nelson, G.S.

1979-01-01

The parameters involved in the induction of resistance against Schistosoma mansoni by injection of irradiated, artificially transformed schistosomula were studied in mice. Single intramuscular injections of 500 schistosomula exposed to radiation doses in the range 2.3 to 160 krad. resulted in significant protection ( in the range 20 to 50% as assessed by reduced worm burdens) against a challenge infection administered at intervals from 3 to 24 weeks post-vaccination. However, schistosomular irradiated with 20 krad. consistently resulted in better protection than those exposed to either higher or lower radiation doses despite the persistence of stunted adults from the infections irradiated with 2.3 krad. Vaccination with 40 krad. schistosomula resulted in significant protection in terms of reduced worm and tissue egg burdens and increased survival following lethal challenge. Varying the number of irradiated schistosomula, the frequency and route of their administration, the site of challenge and the strain of host all failed to enhance the level of resistance. However, percutaneously applied, irradiated cercariae were found to be more effective in stimulating resistance (60%) than intramuscularly injected, irradiated schistosomula (40%). (author)

Activation of chromatin degradation by a protein factor of thymocyte cytoplasm of irradiated mice

International Nuclear Information System (INIS)

Soldatenkov, V.A.; Filippovich, I.V.

1986-01-01

A cytoplasmic thymocyte fraction isolated 1 h after irradiation of mice accelerates chromatin degradation in isolated nuclei. Treatment of the cytoplasmic fraction by heat and injection of cycloheximide to mice prevent the acceleration of DNA degradation. The analysis of the chromatin degradation products and the kinetics of this process at acid and alkaline pH shows that activation of DNA degradation in thymocytes by a factor obtained from the irradiated cell cytoplasm is specific for a Ca 2+ , Mg 2+ -dependent enzyme. The time- and dose-dependent parameters of the appearance in the thymocyte cytoplasm of the factor influencing degradation of chromatin are in a good agreement with both the time of the onset of its postirradiation degradation and the dose dependence of this process

Some genetic profiles in liver of Ehrlich ascites tumor-bearing mice under the stress of irradiation

Directory of Open Access Journals (Sweden)

Amal I. Hassan

2014-04-01

Full Text Available Radiation therapy aims to kill cancer cells with a minimum of normal tissue exposure. In an attempt to define the molecular and biochemical changes associated with exposure to radiotherapy, the objective of the present study is to explore the effect of gamma (γ irradiation on nuclear factor, erythroid 2 (NFE2, P53, stromelysin-1 (matrix metalloproteinase-3 (MMP3, BCL-2 and BAX genes expression in Ehrlich ascites carcinoma (EAC bearing mice. Various biochemical parameters such as liver function, H2O2, B% and T% lymphocytes, total antioxidants and MDA were investigated to evaluate their usefulness as possible during cancer treatment with radiotherapy. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 0.5 Gy. Sixty-four female mice, weighing 20–25 g were used in this study and divided into three main groups. The first group served as control group, while the second were injected intraperitoneally with EAC then was subdivided into two groups, II A and II B. The latter one (group II B, the animals were exposed to a single dose of 0.5 Gy whole body γ irradiation. The third main group, were irradiated with a single dose of 0.5 Gy whole body γ irradiation. Blood and liver tissue samples were collected at 4, 24 and 96 h post-irradiation. The gene expression levels in the livers of animals from each exposure group were compared individually with that of pooled sham-irradiated animals. MMP3 and NFE2 were overexpressed in liver samples of EAC group post 4, 24 and 96 h of γ irradiation (IIB. On the other hand, P53 and BCL-2 genes were downregulated by using RT-PCR analysis post 4, 24 and 96 h of γ irradiation (IIB. As well as, liver function and MDA were increased significantly in the γ - irradiation group (3rd group when compared to control mice (1st group. Gamma irradiation 3rd group revealed increase in the level of T% and B% lymphocytes. According to the obtained results, both γ rays and time period alter

Chloroquine Engages the Immune System to Eradicate Irradiated Breast Tumors in Mice

International Nuclear Information System (INIS)

Ratikan, Josephine Anna; Sayre, James William; Schaue, Dörthe

2013-01-01

Purpose: This study used chloroquine to direct radiation-induced tumor cell death pathways to harness the antitumor activity of the immune system. Methods and Materials: Chloroquine given immediately after tumor irradiation increased the cure rate of MCaK breast cancer in C3H mice. Chloroquine blocked radiation-induced autophagy and drove MCaK cells into a more rapid apoptotic and more immunogenic form of cell death. Results: Chloroquine treatment made irradiated tumor vaccines superior at inducing strong interferon gamma-associated immune responses in vivo and protecting mice from further tumor challenge. In vitro, chloroquine slowed antigen uptake and degradation by dendritic cells, although T-cell stimulation was unaffected. Conclusions: This study illustrates a novel approach to improve the efficacy of breast cancer radiation therapy by blocking endosomal pathways, which enhances radiation-induced cell death within the field and drives antitumor immunity to assist therapeutic cure. The study illuminates and merges seemingly disparate concepts regarding the importance of autophagy in cancer therapy

Prenatal irradiation and spatial memory in mice: investigation of dose-response relationship

International Nuclear Information System (INIS)

Sienkiewicz, Z.J.; Haylock, R.G.E.; Saunders, R.D.

1994-01-01

Pregnant CD1 mice were exposed on gestational day 18 to 250 kV X-rays at 0.1, 0.25, 0.35 and 0.5 Gy. The performances of 10 adult male offspring from each exposure condition were investigated on a spatial discrimination learning task in a radial arm maze. An impairment in the performance of this task was found which showed a correlation with dose. Compared with sham exposed control mice, performance was not significantly affected with irradiation at 0.1 Gy and was slightly but non-significantly reduced at 0.25 Gy. Irradiation at 0.35 Gy caused a significant impairment in performance, and exposure at 0.5 Gy resulted in a still larger impairment. The overall association between dose and behavioural impairment was best described by a linear relationship without a threshold, although at doses lower than about 0.25 Gy any impairment would appear to be too small to be detectable. (Author)

CD133-targeted Gene Transfer Into Long-term Repopulating Hematopoietic Stem Cells

NARCIS (Netherlands)

Brendel, Christian; Goebel, Benjamin; Daniela, Abriss; Brugman, Martijn; Kneissl, Sabrina; Schwaeble, Joachim; Kaufmann, Kerstin B.; Mueller-Kuller, Uta; Kunkel, Hana; Chen-Wichmann, Linping; Abel, Tobias; Serve, Hubert; Bystrykh, Leonid; Buchholz, Christian J.; Grez, Manuel

Gene therapy for hematological disorders relies on the genetic modification of CD34(+) cells, a heterogeneous cell population containing about 0.01% long-term repopulating cells. Here, we show that the lentiviral vector CD133-LV, which uses a surface marker on human primitive hematopoietic stem

The combined influence of irradiation and stress on antibody formation in mice

International Nuclear Information System (INIS)

Surinov, B.P.; Karpova, N.A.

1996-01-01

Disturbances in humoral immune response to sheep erythrocytes after separate and combined effect of ionizing radiation (2 and 4 Gy) and stress (swimming for 10 of 60 min) was studied in mice. The increase in sensitivity to stress was found in irradiated mice. Superposition of undulating dynamics of post-stress immunosuppression on dynamics of post-radiation disorder was revealed. This is due to the different mechanisms of disturbances: redistribution of precursors of immunocompetent cells between immune organs in the first case and destruction of cells in the second case. 17 refs., 2 figs

The effect of ceruloplasmin on erythroid precursor cells in the marrow of irradiated mice

International Nuclear Information System (INIS)

Suda, Toshio; Miura, Yasusada; Ozawa, Keiya; Yamada, Masaaki.

1981-01-01

The effect of ceruloplasmine on erythroid colony forming unit (CFU-e) of irradiated mice was investigated. Whole body #betta# ray irradiation of 100rad decreased the number of CFU-e from 154 to 40 per 4 * 10 4 myeloid nucleated cells. When human #betta#-globulin of 1 mg/kg or ceruloplasmin of 1 mg/kg was administrated immediately after irradiation, the number of CFU-e increased to that of more than normal and normal value in 2 days, respectively. In the case where ceruloplasmin was begun to administrated 7 days before irradiation, though the CFU-e number decreased from 144 to 44, the number increased to 317 after 2 days, and gradually decreased to the normal value by 16 days after irradiation. (Nakanishi, T)

Radioprotection of vitamin D on mice injured by irradiation

International Nuclear Information System (INIS)

Wang Xiaohui; Zhou Zhengyu; Li Bingyan; Nie Jihua; Tong Jian; Zhang Zengli

2008-01-01

To investigate the radioprotective effect of vitamin D against irradiation injury, the mice exposed to 60 Co γ-rays at 6 Gy was treated with preparation of vitamin D(Alfacalcidol Soft Capsules). Cell cycle and apoptosis was analyzed by flow cytometry (FCM) following staining of cells with propidium iodide (PI). Peripheral blood cell counts were analyzed by autoanalyzer. It has been found that vitamin D significantly increases white blood cell (WBC) counts, decreases bone marrow PEC micronucleus rate. FCM analysis shows that compared with damaged group, G2 and S phases of bone marrow cells in vitamin D protection group increases significantly at 24 h after whole body irradiation, whereas G1 phase cells decrease at the same times. So vitamin D might be a new radioprotection agent and it should be deserved further study. (authors)

Effects of feeding lactobacillus GG on lethal irradiation in mice

International Nuclear Information System (INIS)

Dong, M.Y.; Chang, T.W.; Gorbach, S.L.

1987-01-01

Mice exposed to 1400 rads of total body irradiation experienced 80%-100% mortality in 2 wk. Bacteremia was demonstrated in all dead animals. Feeding Lactobacillus GG strain reduced Pseudomonas bacteremia and prolonged survival time in animals colonized with this organism. In animals not colonized with Pseudomonas, feeding Lactobacillus GG also produced some reduction in early deaths, and there was less Gram-negative bacteremia in these animals compared with controls

The protective effect of Sambucus ebulus against lung toxicity induced by gamma irradiation in mice

Directory of Open Access Journals (Sweden)

Mohammad Karami

2015-01-01

Full Text Available The aim of present study was to investigate the potential antioxidant and lung protective activities of Sambucus ebulus (SE against toxicity induced by gamma irradiation. Hydroalcoholic extract of SE (20, 50 and 100 mg/kg was studied for its lung protective activity. Phenol and flavonoid contents of SE were determined. Male C57 mice were divided into ten groups with five mice per group. Only the first and second groups (as negative control received intraperitoneally normal saline fluid. Groups 3 to 5 received only SE extract at doses of 20 mg/kg, 50 mg/kg and 100 mg/kg intraperitoneally; three groups were repeatedly injected for 15 days as chronic group. Groups 6 to 8 received a single-dose of gamma irradiation just 2 hours before irradiation as acute group. The ninth and tenth groups (as positive control received only gamma rays. Animal was exposed whole-body to 6 Gy gamma radiation. After irradiation, tissue sections of lung parenchyma were examined by light microscope for any histopathologic changes. SE at doses 50 and 100 mg/kg improved markedly histopathological changes induced by gamma irradiation in lung. Lung protective effect of SE could be due to attention of lipid peroxidation. Our study demonstrated that SE as a natural product has a protective effect against lung toxicity induced by   gamma irradiation in animal.

Experimental study on lyophilized irradiation sterilized nerve allografts in rabbits

International Nuclear Information System (INIS)

Yang Zhiyuan; Sun Shiquan; Liu Hechen

1991-01-01

Lyophilized irradiation sterilized nerve grafts in rabbits were used in allogeneic nerve transplantation. The result show that about 76% of experimental rabbits had fairly well morphologic (microscopic and electron microscopic) and electrophysiological recovery 3 month after operation. Preservation of neurilemmal tubes in nerve grafts, repopulation of Schwann cells in this tube and suppression of immune rejection are the key points in allogeneic nerve transplantation

Effect of x-irradiation on cell kinetics of esophageal membrane cells in mice

International Nuclear Information System (INIS)

Ando, Koichi; Tsunemoto, Hiroshi; Urano, Muneyasu; Koike, Sachiko

1977-01-01

Effect of x-irradiation on the cell kinetics of esophageal membrane cells was studied in C3Hf/He male mice. Experimental methods include; counting the number of basal and superficial cells, and pulse or continuous labelling by tritiated thymidine. Esophageal area was irradiated with 1000 rad of 200 kVp x-rays and cell kinetics were studied on the 5th post-irradiation day. Autoradiography revealed the shortening of the cell cycle time, specifically in G- and G- phases. Numbers of basal cells and of superficial cells were found to increase for 5 days after irradiation. Continuous labelling experiments using infusion technique demonstrated than growth fraction of irradiated basal cells was 1.0 as well as that of non-irradiated cells. It was of interest that the migration time, i.e., the time required for labelled cells to migrate from basal cell layer to superficial cell layer, was shortened approximately 1/3 of that of non-irradiated control after irradiation. Diurnal variation was observed not only in normal basal cells but also in irradiated ones, and the rate of increase of labelling index after continuous labelling was independent of the time when the labelling was started. (auth.)

Effect of x irradiation on cell kinetics of esophageal membrane cells in mice

Energy Technology Data Exchange (ETDEWEB)

Ando, K; Tsunemoto, H; Urano, M; Koike, S [National Inst. of Radiological Sciences, Chiba (Japan)

1977-05-01

Effect of x irradiation on the cell kinetics of esophageal membrane cells was studied in C3Hf/He male mice. Experimental methods include; counting the number of basal and superficial cells, and pulse or continuous labelling by tritiated thymidine. Esophageal area was irradiated with 1000 rad of 200 kVp x rays and cell kinetics were studied on the 5th post-irradiation day. Autoradiography revealed the shortening of the cell cycle time, specifically in G- and G- phases. Numbers of basal cells and of superficial cells were found to increase for 5 days after irradiation. Continuous labelling experiments using infusion technique demonstrated than growth fraction of irradiated basal cells was 1.0 as well as that of non-irradiated cells. It was of interest that the migration time, i.e., the time required for labelled cells to migrate from basal cell layer to superficial cell layer, was shortened approximately 1/3 of that of non-irradiated control after irradiation. Diurnal variation was observed not only in normal basal cells but also in irradiated ones, and the rate of increase of labelling index after continuous labelling was independent of the time when the labelling was started.

Changes in compartments of hemospoietic and stromal marrow progenitor cells after continuous low dose gamma-irradiation

Science.gov (United States)

Domaratskaya, E.; Starostin, V.

The low dose continuous gamma-irradiation chosen corresponded with that affected the organisms onboard a spacecraft (Mitrikas, Tsetlin, 2000). F1 (CBAxC57Bl/6) male and female mice were used at 3 4 months of age. Experimental mice were- irradiated during 10 days to a total dose of 15 mGy (Co60 gamma-sources, mean dose rate of 1.5-2.0 mGy/day). Another group of intact mice served as control. Younger and advanced hemopoietic progenitors measured at day 11 (i.e. CFU -S-11) and day 7 (i.e. CFU-S-7), respectively, after transplantation of test donor cells were assayed by the method of Till and McCulloch (1961). Stromal changes were evaluated by estimation of in vitro fibroblastic colony-forming units (CFU -F ) content and by the ability of ectopically grafted (under renal capsule) stroma to regenerate the new bone marrow organ. CFU-S-11 number increased of 40% as compared with control and almost 2-fold higher than that of CFU-S-7. The CFU-F content increased almost of 3-fold. Size of ectopic marrow transplants was estimated at day 70 following grafting by counting myelokariocyte and CFU -S number that repopulated the newly formed bone marrow organ. It was found more than 2-fold increase of myelokariocytes in transplants produced by marrow stroma of irradiated donors. CFU -S contents in transplants increased strikingly in comparison to control level. CFU-S-7 and CFU-S-11 increased of 7.5- and of 3.7-fold, respectively, i.e. the rate of advanced CFU - S predominated. It should be noted a good correlation between number of stromal progenitor cells (CFU-F) and ectopic transplant sizes evaluated as myelokaryocyte counts when irradiated donors used. In the same time, if sizes of transplants was measured as CFU-S-7 and CFU - S-11 numbers, their increases were more pronounced. Therefore, continuous low dose gamma- irradiation augments significantly both hemopoietic and stromal progenitor cell number in bone marrow. Additionally, the ratio of distinct CFU -S subpopulations

Leukemic transformation of donor spleen cells following their transplantation into supralethally irradiated mice with pre-existing viral leukemia. [X Radiation

Energy Technology Data Exchange (ETDEWEB)

Kuhnert, P M; OKunewick, J P; Erhard, P

1974-01-01

Fialkow et al. previously reported leukemia induction in donor-type cells after treating patients for acute lymphoblastic leukemia with total-body irradiation and hematopoietic cell transplantation. Utilizing a murine model and paralleling their treatment protocol, we have documented that induction of leukemia can occur in normal donor cells transplanted into Rauscher viral leukemic mice at 0, 1 and 2 days after irradiation. The induction of leukemia in the grafted cells was verified by: the occurrence of splenomegaly; and secondary spleen cell transplants, whereby the secondary donors were transplanted mice still alive at 30 days and the secondary recipients were normal unirradiated mice. The spleen weights of the grafted leukemic mice were found to be significantly greater than those of the controls and all secondary recipients that received spleen cells from the primary grafted leukemic mice also died of leukemia. Verification that the regenerating hematopoietic tissue was from donor (males) and not host source (females) was accomplished by spleen chromosome preparations taken from randomly selected mice at 14 and at 30 days after cell transplantation. In these preparations, the Y chromosome was clearly distinguishable on the basis of size, shape, and differential staining. The data indicate that induction of leukemia after whole-body irradiation and hematopoietic cell transplantation can occur in immunologically matched donor cells when a viral agent is present and that the incidence of this induction is not affected by a time delay between irradiation and transplant.

Increased intestinal mucosal turnover and radiosensitivity to supralethal whole-body irradiation resulting from cholic acid-induced alterations of the intestinal microecology of germfree CFW mice

International Nuclear Information System (INIS)

Mastromarino, A.J.; Wilson, R.

1976-01-01

The prolonged mean survival time of germfree mice, compared to conventional mice, after exposure to 1000-10,000 rad whole-body irradiation has been postulated to be a function of an increased turnover time of the intestinal mucosal cells caused by the absence of free bile acids. To test this hypothesis, the diet of germ-free CFW mice was supplemented with 0.15 percent cholic acid for 2 weeks. The turnover of thymidine-labeled intestinal mucosal cells and the radiosensitivity to supralethal whole-body irradiation were significantly increased compared to germfree controls. There was a positive correlation between increased survivial time after supralethal whole-body irradiation and slower intestinal mucosal turnover time. Germfree mice supplemented with cholic acid had intestinal mucosal turnover times comparable to those of conventionalized controls. Although cholic acid reduces the mean survival time of germfree mice after suppralethal whole-body irradiation, the mean survival value is significantly greater than the conventionalized controls. Supplementing the diet of conventionalized CFW mice with cholic acid did not significantly decrease the intestinal mucosal turnover time nor did it significantly alter their radiosensitivity to supralethal whole-body irradiation. The data suggest that cholic acid is one of the microecological factors responsible for controlling the mucosal renewal rate and the mean survival time after whole-body irradiation

Prenatal deaths and external malformations caused by x-irradiation during the preimplantation period of ddy mice

International Nuclear Information System (INIS)

Ro, Hee Jeong; Choi, Ihl Bhong; Gu, Yeun Wha

1998-01-01

To evaluate the effects of x-irradiation on prenatal deaths, i.e., preimplantation deaths. embryonic deaths, and fetal deaths, and on external malformations in precompacted preimplantation ddy mice. Pregnant mice (n=85), obtained by limiting the mating time to from 6 to 9 A.M., were segregated into 11 groups, The first five groups (n=26) were irradiated with X-ray doses of 0.1, 0.5, 0.75, 1.5, and 3 Gy, respectively, at 24 h post conception (p.c.) of the preimplantation period. The second five (n=27) groups were irradiated at the same X-ray doses, respectively, but at 48 h p.c. of the preimplantation period. The last group (n=32) was the control group. The uterine contents were examined on the 18th day of gestation for prenatal deaths and external malformations. 1) A statistically significant increase in preimplantation deaths with increasing dose was observed in the experimental groups irradiated at 24 h p.c. and in the groups irradiated at 48 h p.c., as compared to the control group. The threshold dose was close to 0.05 Gy and 0.075 Gy for the irradiations at 24 h p.c. and 48 h p.c. respectively. 2) A statistically significant increase in embryonic deaths with increasing dose was observed in all irradiation groups, except the group irradiated with a dose of 0,1 Gy at 48 h p.c.. 3) No fetal deaths were found in any experimental group. 4) In the experimental groups irradiated at 24 h p.c., anomalies increased with statistical significance, as compared with the control group: 2 exencephalies, 2 open eyelids,' 3 anophthalmias, 2 cleft palates. 2 gastroschisis, 1 abdominal wall defect. 1 leg defect, and 2 short tail anomalies; the threshold dose for external malformations was close to 0.2 Gy at 24 h p.c.. In the groups irradiated at 48 h p.c., 1 open eyelid and 2 short tail anomalies were observed, but there was no statistical significance in those malformations. The results of this study reveal that x-irradiation of precompacted preimplantation ddy mice causes not

Irradiated mice lose the capacity to 'process' fed antigen for systemic tolerance of delayed-type hypersensitivity

Energy Technology Data Exchange (ETDEWEB)

Bruce, M G; Strobel, S; Hanson, D G; Ferguson, A