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O Vos

Publications and source records attributed to O Vos.

At least 19 recordsLinked to original sources
PubMed1992

The effects of graded doses of 1 MeV fission neutrons or X rays on the murine hematopoietic stroma.

The acute radiosensitivity in vivo of the murine hematopoietic stroma for 1 MeV fission neutrons or 300 kVp X rays was determined. Two different assays were used: (1) an in vitro clonogenic assay for fibroblast precursor cells (CFU-F) and (2) subcutaneous grafting of femora or spleens. The number of stem cells (CFU-S) or precursor cells (CFU-C), which repopulated the subcutaneous implants, was used to measure the ability of the stroma to support hemopoiesis. The CFU-F were the most radiosensitive, and the survival curves after neutron and X irradiation were characterized by D0 values of 0.75 and 2.45 Gy, respectively. For regeneration of CFU-S and CFU-C in subcutaneously implanted femora, D0 values of 0.92 and 0.84 Gy after neutron irradiation and 2.78 and 2.61 Gy after X irradiation were found. The regeneration of CFU-S and CFU-C in subcutaneously implanted spleens was highly radioresistant as evidenced by D0 values of 2.29 and 1.49 Gy for survival curves obtained after neutron irradiation, and D0 values of 6.34 and 4.85 Gy after X irradiation. The fission-neutron RBE for all the cell populations was close to 3 and varied from 2.77 to 3.28. The higher RBE values observed for stromal cells, compared to the RBE of 2.1 reported previously for hemopoietic stem cells, indicate that stromal cells are relatively more sensitive than hemopoietic cells to neutron irradiation.

Animals↗
PubMed1991

Developments in modern hematology.

In the past 40 years our concepts about hemopoiesis have been changed dramatically. The results of bone marrow transplantation into lethally irradiated mice since the mid-fifties suggested the existence of a hemopoietic stem cell, which was initially identified as a spleen colony forming cell (CFU-S). Later experiments showed that the stem cell compartment is rather heterogeneous and that the most primitive stem cell, unlike the CFU-S, has the ability for long-term engraftment of an irradiated recipient. Daughter cells of such primitive quiescent stem cells lose their capacity for self-generation gradually with each mitosis and become more and more committed to a specific differentiation lineage. In vitro culture techniques in a serum-free semi-solid medium enabled the establishment and analysis of specific hemopoietic growth factors. Such factors, which are essential for the maintenance, proliferation and differentiation of progenitor cells and the functional activity of mature cells can now be produced with recombinant DNA techniques in pure form and large quantities. Hemopoiesis requires an appropriate microenvironment, consisting of various stromal cell types and an extracellular matrix. Intercellular contacts, adhesion of cells and growth factors to the matrix molecules seem essential in the regulating action of this hemopoietic microenvironment. In long-term bone marrow cultures the development of a stromal hemopoietic microenvironment can facilitate long-term maintenance of stem cells and hemopoietic differentiation. For bone marrow transplantation and infusion of hemopoietic growth factors many clinical indications are well established and our possibilities to interfere in the regulation of hemopoiesis are still growing.

Animals↗
PubMed1991

The effects of x-irradiation on hematopoietic stem cell compartments in the mouse.

The sensitivity for x-irradiation of a series of hematopoietic stem cell populations has been determined. The most primitive cells identified, cells with marrow-repopulating ability (MRA), showed the highest degree of radioresistance. These MRA cells which generate many secondary day-twelve spleen colony-forming units (MRA[CFU-S-12]) or colony-forming units in culture (MRA[CFU-C]) in the marrow of primary recipients had Do values equal to 1.18 and 1.13 Gy, respectively. The more mature CFU-S-12 had intermediate radiosensitivity (Do = 0.94 Gy), whereas the less primitive CFU-S-7 were the most radiosensitive (Do = 0.71 Gy). The in vitro colony-forming precursor cells (CFU-C) showed low radiosensitivity. These data clearly show that the most primitive hematopoietic stem cell measured is less sensitive to ionizing radiation than generally has been assumed on the basis of measurements on CFU-S-7 or CFU-S-12.

Animals↗
PubMed1989

Effects and consequences of prenatal irradiation.

After a brief introduction about the historic development of risk estimates and maximum permissible doses of ionizing radiation, the risks of prenatal irradiation are discussed. Experimental data mainly obtained with mice indicate that the most important risk exists during the period of organogenesis and concerns the induction of malformations. Although in man this period lies between about 10 and 80 days after fertilization for most organs, the main development of the brain occurs later, namely between the 8th and 15th week after conception. Data from Japanese victims of the atomic bomb explosions above Hiroshima and Nagasaki indicate that during development the brain is the most sensitive organ to irradiation and maximal sensitivity is found between the 8th and 15th week after fertilization. A dose of one Gray received during this period induces a severe mental retardation in about 45% of the newborns. The dose response relationship is not significantly different from a linear one without a threshold dose. Studies of intelligence and school performance have shown that 1 Gray received during the 8th-15th week causes a shift of the average intelligence of about 30 points. Irradiation before the 8th week and after the 25th week had no effect on intelligence or mental retardation. During the 16th and 25th week sensitivity was about one fourth of that during the 8th-15th week. Although the irradiation of the embryo and fetus should be avoided as much as possible, the new data have led to an abandonment of the so-called 10-day rule. Generally an accidental irradiation of the embryo or fetus of less than 5 cGy is not considered as a medical indication for abortion. Retrospective studies showed that mothers from children who died from leukemia or other childhood tumors, had been subjected to a diagnostic irradiation of the pelvis or lower abdomen more frequently than mothers from children that did not develop a tumor. It has been estimated that prenatal sensitivity for induction of leukemia and tumors is higher than sensitivity after birth. However, it is still in discussion, whether the relationship between prenatal irradiation and a higher incidence of tumors is of a causal nature.

Abnormalities, Radiation-Induced↗
PubMed1988

Radioprotection by glutathione esters and cysteamine in normal and glutathione-depleted mammalian cells.

Monoethyl (MEE) and diethyl (DEE) esters of glutathione (GSH) had the capacity to provide some protection of normal and buthionine sulfoximine (BSO) pretreated cells against X-irradiation. Both compounds appeared to be transported through the cell membrane into the cells. MEE was intracellularly partly hydrolysed to GSH and caused a limited rise of intracellular GSH. DEE was intracellularly mainly converted into MEE and partly into GSH. DEE caused a larger rise of the intracellular GSH content than MEE; it also provided a better radioprotection. Radioprotection by the GSH esters may be explained by an increase of intracellular GSH as well as by the presence of the esters themselves. Cysteamine caused no rise of the intracellular GSH content, thus its radioprotection could not be mediated by an increase of intracellular GSH. When the radiosensitivity of GSH-depleted cells protected by cysteamine was compared with the radiosensitivity of non-GSH-depleted cells similarly protected by cysteamine, it appeared that the GSH-depleted cells remained more sensitive to irradiation. Thus, it seems that in this respect cysteamine cannot fully substitute for endogenous GSH.

Animals↗
PubMed1986

Reduction of intracellular glutathione content and radiosensitivity.

The intracellular glutathione (GSH) content of HeLa, CHO and V79 cells was reduced by incubating the cells in growth medium containing buthionine sulphoximine or diethyl maleate (DEM). Clonogenicity, single-strand DNA breaks (ssb) and double-strand DNA breaks (dsb) were used as criteria for radiation-induced damage after X- or gamma-irradiation. In survival experiments, DEM gave a slightly larger sensitization although it gave a smaller reduction of the intracellular GSH. In general, sensitization was larger for dsb than for ssb, also the reduction of the o.e.r. was generally larger for dsb than for ssb. This may be due to the higher dose rate in case of dsb experiments resulting in a higher rate of radiochemical oxygen consumption. In general, no effect was found on post-irradiation repair of ssb and dsb.

Animals↗
PubMed1986

The influence of oxygen on the induction of radiation damage in DNA in mammalian cells after sensitization by intracellular glutathione depletion.

Treatment of mammalian cells with buthionine sulphoximine (BSO) or diethyl maleate (DEM) results in a decrease in the intracellular GSH (glutathione) and non-protein-bound SH (NPSH) levels. The effect of depletion of GSH and NPSH on radiosensitivity was studied in relation to the concentration of oxygen during irradiation. Single- and double-strand breaks (ssb and dsb) and cell killing were used as criteria for radiation damage. Under aerobic conditions, BSO and DEM treatment gave a small sensitization of 10-20 per cent for the three types of radiation damage. Also under severely hypoxic conditions (0.01 microM oxygen in the medium) the sensitizing effect of both compounds on the induction of ssb and dsb and on cell killing was small (0-30 per cent). At somewhat higher concentrations of oxygen (0.5-10 microM) however, the sensitization amounted to about 90 per cent for the induction of ssb and dsb and about 50 per cent for cell killing. These results strengthen the widely accepted idea that intracellular SH-compounds compete with oxygen and other electron-affinic radiosensitizers with respect to reaction with radiation-induced damage, thus preventing the fixation of DNA damages by oxygen. These results imply that the extent to which SH-compounds affect the radiosensitivity of cells in vivo depends strongly on the local concentration of oxygen.

Animals↗
PubMed1984

Effects of BSO and DEM on thiol-level and radiosensitivity in HeLa cells.

Reduction of the intracellular GSH and NPSH levels in HeLa cells by BSO and DEM treatments was determined. The effect of a 16 to 22 hr incubation with BSO at 37 degrees C, resulting in a depletion of GSH and NPSH to about 10 and 50%, respectively, and the effect of a 50 min incubation with DEM resulting in a reduction of GSH and NPSH to about 30 and 60%, respectively, on radiation sensitivity were studied. As parameters for radiation damage, single and double strand DNA breaks (ssb and dsb) and cell killing were used. Furthermore, repair of ssb and dsb were followed in the first 30 to 120 min after radiation, respectively. BSO and DEM treatment gave a small sensitization for the 3 types of radiation damage (ssb, dsb and cell killing) in aerobic condition. In hypoxic condition the sensitizing effect of both compounds on dsb was larger than the effect on ssb. Pretreatment with BSO and DEM had no influence on repair of ssb and dsb when cells were irradiated in air, but when cells were irradiated in hypoxia, repair was somewhat inhibited after pretreatment with DEM. It can be postulated that a reduction of the intracellular GSH level by BSO and DEM treatment affects cellular radiosensitivity both by a competitive mechanism between GSH and O2 and by inhibition of enzymatic repair of DNA breaks, the latter only in the case of DEM treatment.

Buthionine Sulfoximine↗
PubMed1984

Protection against X-irradiation by some orally administered compounds.

A number of compounds were studied that protected mice against LD50/30 after X-irradiation. For three compounds (WR 109342, WR 158490 and WR 159243) dose reduction factors between 1.7 and 1.8 were obtained after oral administration. Blood taken from mice that had been treated with these protective compounds provided virtually no protection of HeLa cells in vitro, whereas when blood from cysteamine treated mice was tested in vitro, protection could be demonstrated. This may indicate different mechanisms of action.

Adamantane↗
PubMed1983

Short- and long-term effects of whole-body irradiation with fission neutrons or X rays on the thymus in CBA mice.

Young adult (6 weeks old) female CBA mice were exposed to whole-body irradiation with either 2.5-Gy fast fission neutrons of 1 MeV mean energy or 6.0-Gy 300 kVp X rays at centerline dose rates of 0.1 and 0.3 Gy/min, respectively. The weight of spleen and animal and the weight, cellularity, and histological structure of the thymus were studied at different times after irradiation. Thymic recovery after whole-body irradiation showed a biphasic pattern with minima at 5 and 21 days after irradiation and peaks of regeneration at Days 14 and 42 after X irradiation or at Days 14 and 70 after neutron irradiation. After the second phase of recovery, a marked decrease in relative thymus weight and cellularity was observed, which lasted up to at least 250 days after irradiation. Splenic recovery showed a monophasic pattern with an overshoot on Day 21 after irradiation. After neutron irradiation a late decrease in relative spleen and animal weight was observed. The observed late effects on thymus and spleen weight and thymus cellularity are discussed in terms of a persistent defect in the bone marrow.

Animals↗
PubMed1981

Restoration of hemopoiesis by CFU-S from different backgrounds in the mouse.

Liver from 14 day-old fetuses, bone marrow, spleen, and blood from normal adult mice, and bone marrow, spleen, blood, and liver from adult endotoxin (ET)-treated mice were used for isogeneic hemopoietic restoration in lethally whole-body irradiated mice. The number of CFU-S required to prevent 50% mortality of irradiated mice was about 3 for fetal liver, 7-10 for bone marrow, 20 for normal blood and for blood, liver, and spleen of ET-treated mice, and 80 for spleen of normal mice. CFU-S growth curves in femoral bone marrow and spleen showed some variations but the differences in survival of irradiated and protected mice could not easily be explained by differences in CFU-S growth curves. It can be concluded that the CFU-S from peripheral blood, although somewhat less effective than CFU-S from bone marrow, can be a valuable source of CFU-S for bone marrow transplantation.

Animals↗
PubMed1981

Radioprotection by thiazolidines at the cellular level.

Radioprotection by a number of thiazolidine derivatives was studied in vitro. Reproductive integrity of single cells was used as a parameter for survival after irradiation. Thiazolidine itself did not protect when dissolved in culture medium, but a good protective activity was found when it was dissolved in rat blood. Rat blood improved also the radioprotective activity of most other thiazolidine derivatives. The best protection was obtained with thiazolidines in which the carbon at the 2 position was substituted by germanium. No correlation was evident between the degree of protection and release of a free SH group by hydrolysis of the thiazolidine ring. The results support a previous suggestion by Terol, Fernandez, Robbe, Châpat, Granger and Sentenac-Rovmanov (1978) that the thiazolidines proper and not their hydrolysis products are responsible for radioprotection.

Cell Line↗
PubMed1981

Genetic control of lipopolysaccharide-induced mobilization of CFUs. Dissociation between early and delayed mobilization of CFUs in complement C5-deficient mice and LPS non-responder mice.

Lipopolysaccharide (LPS)-induced mobilization of CFUs from haemopoietic tissues into the circulation has a biphasic pattern. The first rise occurs within 30 min of LPS injection, the second 4-7 days later. This second rise coincides with an increase of the CFUs number in the spleen from about 3000 to about 50,000. We have investigated the relationship between the two peaks by making use of complement C5-deficient mouse strains and the LPS non-responder mouse strains C3H/HeJ and C57BL/10ScCr. These latter two strains lack a serologically identifiable structure ('LPS-receptor') which is present in all LPS-responder strains. After injection of eleven different mouse strains with LPS, the numbers of circulating CFUs increased rapidly in all strains, except in the C5-deficient A/J, AKR/J, DBA/2J and B10.D2/oSn mice. On the other hand, the delayed LPS-induced accumulation of CFUs in blood and spleen occurred in all mouse strains tested, including the C5-deficient strains, but not in the LPS non-responder strains C3H/HeJ and C57BL/10ScCr. These results show that (a) early LPS-induced mobilization of CFUs is dependent on the availability of C5, in contrast to the delayed CFUs accumulation in blood and spleen, (b) the presence of the LPS receptor is not required for early CFUs mobilization by LPS and (c) recognition of the mobilizing agent by a specific receptor is required for the delayed accumulation of CFUs in blood and spleen.

Animals↗
PubMed1980

Effects of serum complement levels on the mobilization of mature white blood cells in relation to mobilization of CFUS.

It was investigated whether the complement dependency of CFUS mobilization observed for certain mobilizing agents is unique for the CFUS compartment, or whether this mobilization reflects a more general mechanism, which involves also the mobilization of mature leukocytes. The number of all recognizable nucleated cell types in the blood was determined following the injection of the mobilizing agents, i.e. endotoxin, zymosan, cobra venom factor, proteinase, trypsin, dextran sulphate and the copolymer of polymethacrylic acid and styrene. The results indicate that if a mobilizing effect of a CFUS mobilizing agent on other nucleated cells occurs, this mobilization of nucleated cells is similarly inhibited or not by C3 to C9 depletion as is observed for the CFUS mobilization. The degree of inhibition is also comparable to the inhibition of CFUS mobilization. The significance of the complement system for the mobilization process is discussed.

Animals↗
PubMed1979

Further studies on mobilization of CFUs.

Mobilization of CFUs from haemopoietic tissues into circulation was studied after injection of different bacterial lipopolysaccharides (LPS), zymosan, phytohaemagglutinin (PHA), concanavalin A (Con A), trypsin and di-isopropyl-fluorophosphate-inhibited trypsin. All bacterial LPS used gave an increase of CFUs in the peripheral blood at 1 h after i.v. injection. Some variation in activity could not be excluded. As with Salmonella typhosa LPS, zymosan gave an increase in circulating CFUs during the first few hr and a second peak a few days later. After injection of zymosan as well as S. typhosa LPS the second peak in the blood was accompanied by a large increase in CFUs numbers in the spleen. PHA gave an immediate mobilization of CFUs, but the mobilization after injection of Con A during the first few hr occurred more slowly. After injection of S. typhosa LPS, zymosan and PHA the blood C3 level was found to be depressed considerably. This might indicate that the complement system is involved in the early mobilization of CFUs. Dexamethasone, a synthetic hormone which has been reported to give sequestration of several cell types in the bone marrow, did not inhibit the early and late mobilization of CFUs which normally occurs after injection of S. typhosa LPS.

Animals↗
PubMed1979

Studies on the mechanism of haemopoietic stem cell (CFUs) mobilization. A role of the complement system.

A variety of substances can mobilize haemopoietic stem cells (CFUs) into the peripheral blood. In this study the involvement of the complement system in the mobilization process was investigated. Pretreatment of mice with the complement-activating factor of cobra venom (CoF), which lowered the serum C3 levels to 10-25% of the normal value, could completely prevent CFUs mobilization induced by high doses of CoF, endotoxin (ET) from Salmonella typhosa, inulin, zymosan and the proteolytic enzymes proteinase and trypsin. On the other hand, mobilization induced by the polyanions dextran sulphate and the copolymer of polymethacrylic acid and styrene could not be prevented, or at least affected only slightly. There appears to be a relationship between the extent of decomplementation by CoF and the extent of CFUs mobilization induced by ET. The results indicate that certain agents mobilize CFUs via the complement system, whereas other agents induce CFUs mobilization independent of the availability of complement components.

Animals↗