Some Observations on the Epidemiology and the Pathology of Reticulum Cell Sarcomas in (C57BL/Cne x C3H/Cne) F1 Mice

1973 ◽  
Vol 59 (2) ◽  
pp. 97-118 ◽  
Author(s):  
Vincenzo Covelli ◽  
Pietro Metalli ◽  
Bruno Bassani ◽  
Benito Di Caterino ◽  
Giovanni Silini
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Lethal Dose ◽  
Whole Body ◽  
Single Type ◽  
Reticulum Cell ◽  
Neoplastic Cells ◽  
Virus Like Particles ◽  
Mesenteric Node ◽  
X Irradiation

Life-long observations on untreated animals have shown that spontaneous reticulum cell sarcomas (RCS) developed in 56.5 % male mice of the hybrid (C57BL/Cne x C3H/Cne) F1 strain; the average age at death of mice with tumors was 949 days, compared with 929 days for all causes: no age-specific peak of mortality has been shown to occur over the entire life span of the animals. Histologically, the spleen and all the lymphnodes, including the mesenteric node, were always invaded; neoplastic growth was found less frequently in kidneys, liver and lungs (77, 70, and 40%, respectively), only occasionally in other organs such as adrenals and testes, and never in the thymus. The tumor was predominantly composed of a single type of neoplastic cells, resembling highly undifferentiated reticular cells, typically proliferating from the periarteriolar region of the lymphatic follicles in the spleen. The monomorphic aspect of the tumor cell population suggests that RCS in this strain of mice may be classified as type A according to Dunn. Electron-microscopy observations showed the presence of a few virus-like particles both in tumor cells and in sediments from cell-free extracts. Transplantation of cells from spontaneous RCS into both normal and lethally-irradiated syngeneic recipients was successful only in 4 out of 7 experiments, regardless of the tissue of origin of the neoplastic cells (spleen, lymphnodes or bone marrow). Virus-like particles were seen with higher frequency in transplanted tumors. Inoculation of cell-free extracts into neonatal mice of low-leukemia strains has not so far been successful. Splenectomy of young animals as well as the intravenous injection of syngeneic bone marrow cells immediately following a lethal dose of whole-body X-irradiation significantly reduced the frequency of spontaneous tumors.

scholarly journals Radioprotective Effects of Gallic Acid in Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Gopakumar Gopinathan Nair ◽  
Cherupally Krishnan Krishnan Nair
Keyword(s):  
Bone Marrow ◽  
Gamma Radiation ◽  
Gallic Acid ◽  
Chromosomal Aberrations ◽  
Bone Marrow Cells ◽  
Membrane Lipids ◽  
Lethal Dose ◽  
Whole Body ◽  
Radiation Induced ◽  
Marrow Cells

Radioprotecting ability of the natural polyphenol, gallic acid (3,4,5-trihydroxybenzoic acid, GA), was investigated in Swiss albino mice. Oral administration of GA (100 mg/kg body weight), one hour prior to whole body gamma radiation exposure (2–8 Gy; 6 animals/group), reduced the radiation-induced cellular DNA damage in mouse peripheral blood leukocytes, bone marrow cells, and spleenocytes as revealed by comet assay. The GA administration also prevented the radiation-induced decrease in the levels of the antioxidant enzyme, glutathione peroxidise (GPx), and nonprotein thiol glutathione (GSH) and inhibited the peroxidation of membrane lipids in these animals. Exposure of mice to whole body gamma radiation also caused the formation of micronuclei in blood reticulocytes and chromosomal aberrations in bone marrow cells, and the administration of GA resulted in the inhibition of micronucleus formation and chromosomal aberrations. In irradiated animals, administration of GA elicited an enhancement in the rate of DNA repair process and a significant increase in endogenous spleen colony formation. The administration of GA also prevented the radiation-induced weight loss and mortality in animals (10 animals/group) exposed to lethal dose (10 Gy) of gamma radiation. (For every experiment unirradiated animals without GA administration were taken as normal control; specific dose (Gy) irradiated animals without GA administration serve as radiation control; and unirradiated GA treated animals were taken as drug alone control).

scholarly journals HEMOPOIETIC COLONY STUDIES

1968 ◽  
Vol 127 (1) ◽  
pp. 205-214 ◽  
Author(s):  
N. S. Wolf ◽  
J. J. Trentin
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Whole Body ◽  
Marrow Cavity ◽  
Normal Spleen ◽  
Colony Forming Units ◽  
X Irradiation ◽  
Marrow Stroma ◽  
Exogenous Origin ◽  
Bone Marrow Regeneration

In heavily irradiated mice, bone marrow regeneration of either endogenous or exogenous origin was shown to occur in discrete foci comparable to the more intensively studied spleen colonies. The number of endogenous bone marrow colonies was inversely related to dose of whole body X-irradiation. Endogenous marrow colonies were found after higher doses of irradiation than were endogenous spleen colonies. Most of them were granulocytic in nature. Exogenous bone marrow colonies in lethally irradiated mice injected with bone marrow cells were proportional in number to the dose of cells injected, appeared at a time comparable to spleen colonies like which, at 7 or 8 days, they were of single differentiated cell line, either granuloid or erythroid or megakaryocytic, with a small percentage of "mixed" colonies. Whereas erythroid colonies outnumber granuloid colonies in spleen, either in situ or subcutaneously transplanted (E:G colony ratio of about 3.5), granuloid colonies outnumber erythroid in bone marrow (E:G colony ratio of about 0.7). The characteristic E:G colony ratios of spleen and marrow appear more likely to be the result of a hemopoietic organ stromal influence on pluripotent colony forming units (CFU's) than of selective lodgment of committed (unipotent) granuloid and erythroid CFU's in bone marrow and spleen, respectively, as indicated by the following. Bone marrow stem cells (CFU) which had reseeded the marrow cavity of irradiated primary recipients 18–24 hr earlier, were reharvested and retransplanted intravenously into irradiated secondary hosts. The E:G colony ratio of the colonies formed in the spleen of the secondary hosts was typical of primary spleen colonies (2.8), that of the colonies formed in the marrow cavity was typical of bone marrow colonies (0.6). Pieces of marrow stroma containing reseeded CPU's from the contralateral femur of these same primary recipients were implanted by trocar directly into the spleens of other irradiated secondary recipients. Those CPU's that developed in the intrasplenic-implanted marrow stroma yielded an. E:G colony ratio of 0.1. Those that migrated into the contiguous and remote portions of the spleen gave E:G colony ratios of 2.9 and 2.4, respectively. Irradiated marrow stroma and normal spleen CPU's (a 1 mm cube of spleen) were loaded into the same trocar and implanted directly into the spleens of irradiated mice. The spleen CFU's that migrated into the implanted marrow stroma yielded five granuloid and two mixed colonies. The larger number that developed in the host spleen yielded an E:G colony ratio of 2.9 or higher. Of those 19 mixed colonies that bridged the junction of spleen and implanted marrow stroma in each of the above two experiments, in every case, the erythroid portion of the colony was in the splenic stroma, the granuloid portion was in the marrow stroma.

scholarly journals Hematopoietic Recovery after Transplantation CD117+B220- (lacZ+) Bone Marrow Cells in Lethally Irradiated Mice

2008 ◽  
Vol 51 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Miroslav Hodek ◽  
Jiřina Vávrová ◽  
Zuzana Šinkorová ◽  
Jaroslav Mokrý ◽  
Stanislav Filip
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Repair Process ◽  
Whole Body ◽  
Lacz Gene ◽  
Colony Forming Units ◽  
The Difference ◽  
Macrophage Colony ◽  
Marrow Cells

Experiments presented here were aimed at the description of hematopoiesis repair and in vivo homing of transplanted separated CD117+B220–bone marrow cells after whole-body lethal irradiation at LD 9Gy. ROSA 26 mice were used as donors of marrow cells for transplantation [B6;129S/Gt (ROSA)26Sor] and were tagged with lacZ gene, and F2 hybrid mice [B6129SF2/J] were used as recipients of bone marrow transplanted cells. Hematopoiesis repair was provided by transplantation, both suspension of whole bone marrow cells (5x106) and isolated CD117+B220–cells (5x104). Mice survived up to thirty days after irradiation. We demonstrated that transplantation of suspension of whole bone marrow cells led to faster recovery of CFU-GM (Granulocyte-macrophage colony forming units) in bone marrow and in the spleen too. It is not clear what the share of residential and transplanted cells is in the repair process. Our results demonstrate that sufficient hematopoietic repair occurs after transplantation of CD117+B220–(lacZ+) in lethally irradiated mice, and the difference in CFU-GM numbers in the bone marrow and spleen found on day 8 posttransplant has no influence on the survival of lethally irradiated mice (30 days follow-up).

scholarly journals Myelosuppressive conditioning is required to achieve engraftment of pluripotent stem cells contained in moderate doses of syngeneic bone marrow

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 939-948 ◽  
Author(s):  
Y Tomita ◽  
DH Sachs ◽  
M Sykes
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Whole Body ◽  
Mixed Chimerism ◽  
Hematopoietic Stem ◽  
Donor Cells ◽  
Donor Type ◽  
Low Levels

Abstract We have investigated the requirement for whole body irradiation (WBI) to achieve engraftment of syngeneic pluripotent hematopoietic stem cells (HSCs). Recipient B6 (H-2b; Ly-5.2) mice received various doses of WBI (0 to 3.0 Gy) and were reconstituted with 1.5 x 10(7) T-cell-depleted (TCD) bone marrow cells (BMCs) from congenic Ly-5.1 donors. Using anti-Ly-5.1 and anti-Ly-5.2 monoclonal antibodies and flow cytometry, the origins of lymphoid and myeloid cells reconstituting the animals were observed over time. Chimerism was at least initially detectable in all groups. However, between 1.5 and 3 Gy WBI was the minimum irradiation dose required to permit induction of long-term (at least 30 weeks), multilineage mixed chimerism in 100% of recipient mice. In these mice, stable reconstitution with approximately 70% to 90% donor-type lymphocytes, granulocytes, and monocytes was observed, suggesting that pluripotent HSC engraftment was achieved. About 50% of animals conditioned with 1.5 Gy WBI showed evidence for donor pluripotent HSC engraftment. Although low levels of chimerism were detected in untreated and 0.5-Gy-irradiated recipients in the early post-BM transplantation (BMT) period, donor cells disappeared completely by 12 to 20 weeks post-BMT. BM colony assays and adoptive transfers into secondary lethally irradiated recipients confirmed the absence of donor progenitors and HSCs, respectively, in the marrow of animals originally conditioned with only 0.5 Gy WBI. These results suggest that syngeneic pluripotent HSCs cannot readily engraft unless host HSCs sustain a significant level of injury, as is induced by 1.5 to 3.0 Gy WBI. We also attempted to determine the duration of the permissive period for syngeneic marrow engraftment in animals conditioned with 3 Gy WBI. Stable multilineage chimerism was uniformly established in 3-Gy-irradiated Ly-5.2 mice only when Ly-5.1 BMC were injected within 7 days of irradiation, suggesting that repair of damaged host stem cells or loss of factors stimulating engraftment may prevent syngeneic marrow engraftment after day 7.

Protective effect of artificially induced ‘hibernation’ against lethal doses of whole body x-irradiation in CF1 male mice

1959 ◽  
Vol 196 (6) ◽  
pp. 1211-1213 ◽  
Author(s):  
Sondra M. Kuskin ◽  
S. C. Wang ◽  
Roberts Rugh
Keyword(s):  
Protective Action ◽  
Lethal Dose ◽  
Lethal Effect ◽  
The Body ◽  
Whole Body ◽  
Protective Mechanism ◽  
Slight Reduction ◽  
Male Mice ◽  
Degree Of Protection ◽  
X Irradiation

Hypothermia induced by the use of neuroplegic drugs such as Hydergine, chlorpromazine or promethazine, followed by refrigeration, does not significantly enhance the protective action afforded by refrigeration alone against the lethal dose of whole body x-irradiation in CF1 male mice. The neuroplegic drugs, without refrigeration, provide a slight degree of protection, probably due to the slight reduction in the body temperature. It appears that the action of hypothermia as a protective mechanism depends not on depression of metabolism alone, but on a general depression of bodily processes. Urethane, in conjunction with refrigeration, appears to augment the lethal effect of x-irradiation in the CF1 strain of male mice.

scholarly journals Increases in circulating megakaryocyte growth-promoting activity in the plasma of rats following whole body irradiation

Blood ◽  
1984 ◽  
Vol 63 (5) ◽  
pp. 1060-1066 ◽  
Author(s):  
M Miura ◽  
CW Jackson ◽  
SA Lyles
Keyword(s):  
Bone Marrow ◽  
Plasma Concentration ◽  
Bone Marrow Cells ◽  
Single Cells ◽  
Rat Plasma ◽  
Whole Body ◽  
Growth Promoting ◽  
Marrow Cells

Abstract To gain insight into the regulation of megakaryocyte precursors in vivo, we assayed (in vitro) megakaryocyte growth-promoting activity (Meg-GPA) in plasma of rats in which both marrow hypoplasia and thrombocytopenia had been induced by irradiation. Rats received whole body irradiation of 834 rad from a 137Cs source. Plasma was collected at intervals of hours to days, up through day 21 postirradiation, and was tested, at a concentration of 30%, for Meg-GPA on bone marrow cells cultured in 1.1% methylcellulose with 5 X 10(-5) M 2-mercaptoethanol. With normal rat plasma, no megakaryocyte colonies (defined as greater than or equal to 4 megakaryocytes) were seen and only a few single megakaryocytes and clusters (defined as 2 or 3 megakaryocytes) were formed. Two peaks of plasma Meg-GPA were observed after irradiation. The first appeared at 12 hr, before any decrease in marrow megakaryocyte concentration or platelet count. The second occurred on days 10–14 after irradiation, after the nadir in megakaryocyte concentration and while platelet counts were at their lowest levels. A dose-response study of plasma concentration and megakaryocyte growth, using plasma collected 11 days postirradiation, demonstrated that patterns of megakaryocyte growth were related to plasma concentration; formation of single megakaryocytes was optimal over a range of 20%-30% plasma concentration, while cluster and colony formation were optimal at a plasma concentration of 30%. All forms of megakaryocyte growth were decreased with 40% plasma. There was a linear relationship between the number of bone marrow cells plated and growth of single cells, clusters, and colonies using a concentration of 30% plasma collected 11 days after irradiation. We conclude that irradiation causes time- related increases in circulating megakaryocyte growth-promoting activity. We suggest that the irradiated rat is a good model for studying the relationships between Meg-GPA and megakaryocyte and platelet concentration in vivo.

F-18 Fluorothymidine (FLT) Imaging of the Bone Marrow Compartment in Rats Following Whole Body Irradiation, Stem Cell Transplantation and Spontaneous Recovery.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3529-3529
Author(s):  
Jennifer L. Holter ◽  
Vibhudutta Awasthi ◽  
Kristin Thorp ◽  
Anderson Stacy ◽  
Sandra Bryant ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Conflicts Of Interest ◽  
Lethal Dose ◽  
Whole Body ◽  
Hematopoietic Tissue ◽  
Post Transplantation ◽  
Early Recovery ◽  
Noninvasive Technique ◽  
Imaging Results ◽  
Group 2

Abstract Abstract 3529 Poster Board III-466 Pet imaging using F-18 glucose (FDG) is increasingly being used for evaluation and staging of malignancy. However, staging in hematopoietic tissue using this agent has been hampered by poor specificity. F-18 flourothymidine (FLT) is currently being evaluated clinically as an imaging technique for tumor detection and staging. Secondary to its inclusion in DNA during the S phase, FLT is much more specific to proliferative tissue and less hampered by inflammatory background. As FLT uptake occurs in proliferating cell populations, we attempted to determine if imaging could provide useful information for evaluating global hematopoietic injury and recovery following radiation and transplantation. Three major groups of Wistar-Furth rats were studied. Group 1 consisted of rats receiving 950cGy of Whole Body Irradiation (TBI). Group 2 consisted of rats transplanted with syngeneic bone marrow 24-48 hrs following irradiation. Group 3 consisted of 6 rats exposed to a potentially sub-lethal dose of 500cGy and not transplanted. FLT imaging was performed before irradiation (n=4), 24-48 hrs. following irradiation, and on day 4-5 post transplantation. Subsequent imaging was carried out in 4 transplanted rats on days 8 and 14. Comparative FDG studies were also performed in selected animals. Table 1 summarizes the imaging studies performed in various subsets of rats. Table 1 Imaging Subsets of Experimental Animals and Histologic Correlations Experimental rat subsets FLT # studies performed FDG # studies performed Histologic correlation Normal or baseline rat studies n=10 n=6 Normal cellular marrow 24-48hrs post 950 cGy TBI n=6 n=4 Marrow damage hypocellularity Day 7 post 950 cGy TBI n=4 not done Aplastic marrow Day 6-7 post 950cGy TBI (4-5 days post transplantation) n=4 n=4 Focal areas of cellular regeneration Day 10 post 950 cGy TBI (and transplantation) n=4 n=2 Cellular marrow Day 6-7 post 500cGy TBI (No transplantation) n=6 not done Moderate hypocellularity FLT imaging results were correlated with marrow histology and clinical survival in treated and control groups. Six of 6 irradiated control rats died with marrow aplasia during the second week following 950 cGy. Sub-lethally irradiated and transplanted rats animals showed clear evidence of definitive recovery as early as 6 days post irradiation or 4 days post transplantation respectively. FLT activity of all major marrow sites was easily identified and was superior to FDG images. Findings correlated with histologic evidence of early marrow repopulation and survival. Figure 1 illustrates FLT and FDG imaging performed in normal, post radiation and post transplanted rats. We conclude that FLT imaging represents a practical noninvasive technique to evaluate marrow injury and early recovery following radiation and hematopoietic transplantation. Disclosures: No relevant conflicts of interest to declare.

A novel application of cyclosporine A in nonmyeloablative pretransplant host conditioning for allogeneic BMT

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 1166-1172 ◽  
Author(s):  
Boris Nikolic ◽  
Guiling Zhao ◽  
Kirsten Swenson ◽  
Megan Sykes
Keyword(s):  
Bone Marrow ◽  
Cyclosporine A ◽  
Bone Marrow Cells ◽  
Corticosteroid Treatment ◽  
Marrow Transplant ◽  
Allogeneic Bone Marrow ◽  
Whole Body ◽  
Allogeneic Bone ◽  
Central Tolerance ◽  
Bone Marrow Engraftment

The treatment of mice with anti-CD4 and anti-CD8 monoclonal antibodies (mAbs) on day −5, plus 3 Gy whole body irradiation (WBI) and 7 Gy thymic irradiation (TI) on day 0, allows fully major-histocompatibility-complex–mismatched allogeneic bone marrow engraftment and the induction of immunologic tolerance. TI is required in this model to overcome alloreactivity and possibly to make “space” in the recipient thymus so that lasting central tolerance can be achieved. In addition to suppressing mature T cells in the periphery, Cyclosporine A (CYA) and glucocorticoids have a powerful influence on the thymus. In this study, we evaluated whether the administration of CYA to recipient mice for 12 days prior to bone marrow transplant (BMT), of glucocorticosteroids on the day of BMT, or a combination of both, could create space and overcome alloresistance in the thymus by specifically depleting immature and mature thymocytes prior to BMT. High levels of multilineage donor hematopoietic repopulation and specific transplantation tolerance were achieved in mice treated from days −15 to −3 with CYA (20 mg/kg/d subcutaneously), anti-CD4/CD8 mAbs on day −5, followed by 3 Gy WBI and 15 × 106 allogeneic bone marrow cells on day 0. Vβ analysis suggested a central deletional tolerance mechanism. The same treatment without CYA pretreatment allowed only transient chimerism, without tolerance. Corticosteroid treatment abolished the engraftment-promoting and tolerance-inducing effects of CYA. These results demonstrate a novel pretransplantation-only application of CYA, which facilitates allogeneic marrow engraftment with minimal conditioning, by creating thymic space and/or overcoming intrathymic alloresistance.

scholarly journals Regeneration of blood-forming organs after autologous leukocyte transfusion in lethally irradiated dogs. II. Distribution and cellularity of the marrow in irradiated and transfused animals

Blood ◽  
1976 ◽  
Vol 47 (4) ◽  
pp. 593-601 ◽  
Author(s):  
W Calvo ◽  
TM Fliedner ◽  
E Herbst ◽  
E Hugl ◽  
C Bruch
Keyword(s):  
Bone Marrow ◽  
Normal Values ◽  
Whole Body ◽  
Blood Leukocytes ◽  
X Irradiation ◽  
Trabecular Bones ◽  
Marrow Cellularity ◽  
Number Of Cells

Dogs were given transfusions of cryopreserved autologous mononuclear blood leukocytes after 1200 roentgens (R) (midline dose) whole-body x- irradiation. Bone marrow repopulation was studied by means of histomorphological methods at days 9 and 10 after transfusion of an average of 3 X 10(9), 7 X 10(9), 13 X 10(9), and 31 X 10(9) cells. The return of marrow cellularity to normal values was related to the number of cells transfused. With low cell doses (3 X 10(9) and 7 X 10(9)), the marrow regeneration at 10 days was focal. There were groups of cells (colonies) showing either erythropoiesis, myelopoiesis, or megakaryocytopoiesis in the osteal niches of the trabecular bones. Frequently such niches were seen showing complete cellular recovery next to niches with complete aplasia. With higher cell doses, all niches showed hemopoietic regeneration, and the cellularity approached normal values. No hemopoietic regeneration was observed in those skeletal parts that do not show hemopoiesis, even under normal circumstances.

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