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W Nothdurft

Publications and source records attributed to W Nothdurft.

At least 19 recordsLinked to original sources
PubMed2001

Cell cycle and growth response of CHO cells to X-irradiation: threshold-free repair at low doses.

PURPOSE: To test the hypothesis of a threshold for induced repair of DNA damage (IR) and, secondarily, of hyperradiosensitivity (HRS) to low-dose X-irradiation. METHODS AND MATERIALS: Exponentially growing Chinese hamster ovary cells (CHO) were X-irradiated with doses from 0.2 to 8 Gy. Survival data were established by conventional colony-forming assay and flow-cytometric population counting. The early cell cycle response to radiation was studied based on DNA-profiles and bromodeoxyuridine pulse-labeling experiments. RESULTS: Colony-forming data were consistent with HRS. However, these data were of low statistic significance. Population counting provided highly reproducible survival curves that were in perfect accord with the linear-quadratic (LQ) model. The dominant cell cycle reaction was a dose-dependent delay of G2 M and late S-phase. CONCLUSION: There was no evidence for a threshold of IR and for low-dose HRS in X-irradiated CHO cells. It is suggested that DNA damage repair activity is constitutively expressed during S-phase and is additionally induced in a dose-dependent and threshold-free manner in late S-phase and G2. The resulting survival is precisely described by the LQ model.

Animals↗
PubMed1999

Comparative analysis of apoptosis in HL60 detected by annexin-V and fluorescein-diacetate.

BACKGROUND: Our aim was to compare and evaluate apoptosis formation as detected by propidium-iodide (PI)/annexin-V or PI/fluorescein-diacetate (FDA) as dose-response parameters in a human promyelocytic leukemia cell line, HL60. METHODS: In exponentially growing HL60 cells, apoptosis was induced by ionizing radiation, hyperthermia, topotecan, and cytosine beta-D-arabinofuranoside. At 4 consecutive days following induction, apoptosis was detected by double-labelling, either with PI/annexin-V or PI/FDA. Forward and side scatter, red (PI), and green (FDA or annexin-V) fluorescence were measured by flow cytometry. RESULTS: While light scatter discriminated between morphologically damaged and undamaged cells, fluorescence differentiated vital, apoptotic, and dead cells. Equal proportions of these three subpopulations were detected by both staining techniques. Occasionally, early and mature apoptoses were identified as distinct clusters. During the 4-day observation period, no pronounced maxima of the apoptotic fractions were obtained with either treatment modality. The gradual increases usually showed a delay of 1-2 days. CONCLUSIONS: FDA and annexin-V are equally suitable for detecting apoptosis. Separation improves with time after induction, indicating that, with respect to test specificity, mature apoptoses are superior to early stages. However, the sensitivity towards low rates of apoptosis after weak induction appears limited with both staining procedures.

Annexin A5↗
PubMed1999

Differential proliferation dependence of alpha and beta damage in X-irradiated Chinese hamster cells.

PURPOSE: To determine quantitatively the influence of altering proliferation rates on clonal survival of asynchronously growing Chinese hamster (CHO) cells after X-irradiation and to evaluate the related contribution of alpha and beta damage. MATERIAL AND METHODS: Cell cycle distributions at the time of X-irradiation of CHO cells were assessed by flow cytometry. Clonal radiation survival was established by colony forming assay. Survival data were fitted to the linear-quadratic model and analyzed on the basis of the mean inactivation dose, D. RESULTS: Increased S-phases were associated with increased resistance to X-rays. Radiosensitivity as expressed by D differed by a factor of 1.6 between the most sensitive and the most resistant populations. Separately analyzing the alpha and beta coefficients of survival curves revealed that the proliferation dependent effect was correlated only with beta. The major determinant of D was alpha, but its substantial interexperimental variations were independent of the cell cycle. CONCLUSIONS: Due to altering cell cycle distributions, considerable changes of radiosensitivity can occur. They can in part be understood as a consequence of S-phase dependent alterations of DNA damage repair. Reasons for the changes of a damage dependent lethality remain to be discovered by further research.

Animals↗
PubMed1998

Short-term effects of early-acting and multilineage hematopoietic growth factors on the repair and proliferation of irradiated pure cord blood (CB) CD34+ hematopoietic progenitor cells.

PURPOSE: Hematopoietic growth factor(s) (GF) may exert positive effects in vitro or in vivo on the survival of hematopoietic stem and progenitor cells after accidental or therapeutic total body irradiation. METHODS AND MATERIALS: We studied the clonogenic survival and DNA repair of irradiated (0.36, 0.73, and 1.46 Gy) CD34+ cord blood (CB) cells after short-term incubation (24 h) with GFs. CD34+ cells were stimulated with basic fibroblast growth factor (bFGF), stem cell factor/c-kit ligand (SCF), interleukin-3 (IL-3), IL-6, leukemia inhibitory factor (LIF), and granulocyte-monocyte colony stimulating factor (GM-CSF) alone or in combination in short-term serum-free liquid suspension cultures (LSC) immediately after irradiation and then assayed for clonogenic progenitors. DNA repair was evaluated by analysis of DNA strand breaks using the comet assay. Survival of CFU-GM, BFU-E, and CFU-Mix was determined and dose-response curves were fitted to the data. RESULTS: The radiobiological parameters (D[0] and n) showed significant GF(s) effects. Combination of IL-3 with IL-6, SCF or GM-CSF resulted in best survival for CFU-GM BFU-E and CFU-Mix, respectively. Combinations of three or more GFs did not increase the survival of clonogenic CD34+ cells compared to optimal two-factor combinations. The D[0] values for CFU-GM, BFU-E, and CFU-Mix ranged between 0.56-1.15, 0.41-2.24, and 0.56-1.29 Gy, respectively. As for controls, the curves remained strictly exponential, i.e., all survival curves were strictly exponential without any shoulder (extrapolation numbers n=1 for all tested GF(s). DNA repair capacity of CD34+ cells determined by comet assay, was measured before, immediately after irradiation, as well as 30 and 120 min after irradiation at 1 Gy. Notably, after irradiation the 2-h repair of cytokine-stimulated and unstimulated CD34+ cells was similar. CONCLUSION: Our data indicate that increased survival of irradiated CB CD34+ cells after short-term GF treatment is mediated through proliferative GF effects on the surviving fraction but not through improved DNA repair capacity.

Cell Survival↗
PubMed1998

Hemopoietic progenitor cells in the blood as indicators of the functional status of the bone marrow after total-body and partial-body irradiation: experiences from studies in dogs.

The granulocyte-macrophage colony-forming cells (GM-CFC) were studied in the blood of dogs to evaluate their relationship to the bone marrow GM-CFC under normal conditions and their involvement in hemopoietic regeneration after different types of exposure to ionizing radiation. The GM-CFC could be defined as regular blood elements showing characteristic levels of their concentration in individual dogs in the range from 20 to 300 cells per ml. In relative terms, the GM-CFC numbers present in the whole blood of normal dogs were found to be on the order of 0.1% of the GM-CFC numbers present in the bone marrow. A small fraction of the GM-CFC population in the bone marrow, i.e., about 1%, can be mobilized into the peripheral blood within three h by intravenous injection of dextran sulfate (DS). These cells are characterized by a small size and a low S-phase fraction similar to the GM-CFC that are normally present in the blood. Total-body irradiation with single doses of 0.8 Gy and more caused a characteristic pattern of sequential changes in the blood GM-CFC concentration that were related to the recovery of the bone marrow GM-CFC population. The blood GM-CFC concentration showed an extreme depression within the first 15 days, a transient increase from day 17 to day 35 and remained at subnormal values for several weeks and months. The regeneration of the GM-CFC population in the bone marrow that could be mobilized into the blood by DS was similarly delayed as the recovery of the blood GM-CFC values. In dogs which were kept under continuous radiation exposure (0.019 Gy/day) causing permanent damage to the hemopoietic system, the GM-CFC numbers in the blood remained permanently depressed. Partial-body irradiation of dogs with a myeloablative dose (11.7 Gy) given to the anterior part of their body was followed by sequential changes in the blood GM-CFC concentration specific for this type of exposure. The pattern of changes was determined by direct radiation effects, the compensatory responses in the protected bone marrow and the regeneration events in the irradiated bone marrow. On the other hand, it could be shown that the repopulation and the restoration of the hemopoietic tissue is initiated by the seeding of hemopoietic cells (including GM-CFC) from the protected marrow.

Animals↗
PubMed1997

Acceleration of hemopoietic recovery in dogs after extended-field partial-body irradiation by treatment with colony-stimulating factors: rhG-CSF and rhGM-CSF.

PURPOSE: The influence of treatment with the two colony-stimulating factors, rhG-CSF and rhGM-CSF, on the hemopoietic recovery in aplastic bone marrow sites after extended-field irradiation was studied in a canine model. METHODS AND MATERIALS: The dogs received irradiation of the cranial part of their body with a single dose of 11.7 Gy, comprising approximately 72% of the total bone marrow mass. Anatomically this type of exposure corresponds to upper body irradiation (UBI) as employed under clinical conditions. Treatment with both the CSFs was employed for 7 days by daily injections of 30 microg/kg, starting 24 hr after irradiation. RESULTS: Treatment with rhGM-CSF did not completely prevent the initial decrease of the granulocyte counts, but caused an accelerated, though incomplete, recovery in the period from day 5 to day 15. In contrast, treatment with rhG-CSF caused two phases of granulocytosis and an early recovery to normal levels at day 11 after irradiation. Treatment with rhG-CSF, but not with rhGM-CSF, was associated with a strong supra-normal increase of progenitor cells in the blood within the first 8 days and an accelerated hemopoietic recovery in the irradiated sites particularly within the first 7 days after the exposure. CONCLUSIONS: These results indicate that under conditions of partial-body irradiation short term treatment with G-CSF is superior to GM-CSF in initiating the hemopoietic recovery on the basis of endogenous stem cell seeding.

Animals↗
PubMed1996

Assessment of DNA damage in canine peripheral blood and bone marrow after total body irradiation using the single-cell gel electrophoresis technique.

DNA damage in single peripheral blood (pb) and bone marrow (bm) cells was studied in dogs which were exposed to total body X-ray irradiation (TBI) with a lethal dose of 3.9 Gy. The changes in pb and bm cell numbers were measured within 9 days after TBI. Using the alkaline single-cell gel electrophoresis technique ('comet' assay), DNA strand breaks and alkali labile sites were assessed in single cells derived from the blood before TBI, 1 h and 4 h after TBI and on days 1, 3 and 9 after TBI. Bone marrow cells subjected to the assay were collected before and on days 1 and 9 after TBI. Cells expressing the strongest DNA damage were most frequent in the blood 1 h after TBI and in the bone marrow 1 day after exposure. Thereafter, a continuous reduction of DNA damage in individual cells was observed in the course of progressive leukopenia and granulocytopenia.

Animals↗
PubMed1996

Radiation-induced DNA damage in canine hemopoietic cells and stromal cells as measured by the comet assay.

Stromal cell progenitors (fibroblastoid colony-forming unit; CFU-Fs) are representative of the progenitor cell population of the hemopoietic microenvironment in bone marrow (BM). Previous studies of the radiation dose-effect relationships for colony formation have shown that canine CFU-Fs are relatively radioresistant as characterized by a D0 value of about 2.4 Gy. In contrast, hemopoietic progenitors are particularly radiosensitive (D0 values= 0.12-0.60 Gy. In the present study, the alkaline single-cell gel electrophoresis technique for the in situ quantitation of DNA strand breaks and alkali-labile sites was employed. Canine buffy coat cells from BM aspirates and cells harvested from CFU-F colonies or from mixed populations of adherent BM stomal cell (SC) layers were exposed to increasing doses of X-rays, embedded in agarose gel on slides, lysed with detergents, and placed in an electric field. DNA migrating from single cells in the gel was made visible as "comets" by ethidium bromide staining. Immediate DNA damage was much less in cultured stromal cells than in hemopoietic cells in BM aspirates. These results suggest that the observed differences in clonogenic survival could be partly due to differences in the type of the initial DNA damage between stromal cells and hemopoietic cells.

Animals↗
PubMed1996

Investigation of megakaryopoiesis in myelosuppressed bone marrow using immunogold-silver staining (IGSS).

To determine the frequencies and differential counts of megakaryocytes after cytoreductive treatment in nucleated low-density (1.060 g/ml) bone marrow cells (BMNC) of dogs an immunogold-silver staining (IGSS) technique with the lineage specific monoclonal antibody 2F9 was established. This antibody recognizes the glycoprotein IIb/IIIa complex expressed on the surface of canine megakaryocytes and platelets. The IGSS technique enables not only the detection of megakaryocytes occurring at a low frequency (0.1-0.2%), but also the discrimination between the different maturation stages of megakaryocytes due to cell size, nuclear morphology and cytoplasmic staining. By the use of this technique, small lymphoid megakaryocytic cells were identified. Comparable numbers of megakaryocyte colony-forming cells in 2F9-depleted and nondepleted BMNC suspensions (25.7 +/- 5.0 vs. 25.3 +/- 5.1 Meg-CFC/10(5) BMNC) indicate that these small 2F9 positive cells are nonclonogenic precursors of megakaryoblasts. To prove the applicability of IGSS, serial examinations of bone marrow samples from dogs treated with recombinant human interleukin-6 (IL-6) after exposure to 2.4 Gy total body irradiation (TBI) were performed. The results of the microscopic evaluation indicate that, in the recovery phase after TBI, IL-6 induced an earlier and stronger increase in megakaryocyte frequency in comparison to the control. Interestingly, all maturation stages of the megakaryocytic lineage took part in this IL-6 induced improvement of megakaryocyte recovery.

Animals↗
PubMed1995

Response of hemopoiesis in dogs to continuous low dose rate total body irradiation.

Among the cytotoxic agents which particularly cause damage to cell renewal systems, ionizing radiation is one of the most effective ones since it leads to inactivation of all types of proliferating cells including resting stem cells. It is the aim of this paper to present the effects of continuous low dose rate total body irradiation (TBI) on hemopoiesis in dogs. The animals were exposed to gamma-rays from a 60-Co source, receiving a daily radiation dose of 0.0188 Gy for indefinite times. Sequential hematological studies performed included determinations of peripheral blood cell counts and of total cell numbers in standardized bone marrow samples, assessments of progenitor cells GM-CFC in the blood and bone marrow, and of colony-stimulating activity (CSA) in the serum. The lymphocytes, the thrombocytes and neutrophilic granulocytes uniformly showed early decreases within the first 200 to 500 days corresponding to cumulative radiation doses in the range up to 3.8 to 9 Gy, but remained stable at subnormal levels in the period up to 1,700 days of exposure. The GM-CFC numbers in bone marrow samples from the rib clearly showed a strong decrease within the first 150 days of exposure preceding the changes in the blood granulocyte concentration. A transient partial recovery of the GM-CFC was observed at later times between 700 and 1,200 days of exposure, followed by another decrease to extremely low values at cumulative doses in the range of 32 Gy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Cytokines and progenitor cells of granulocytopoiesis in peripheral blood of patients with bacterial infections.

To investigate the physiological role of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the adaptation mechanisms of myelopoiesis to enhanced demand, we studied both cytokines and their myeloid target cells in hematologically healthy patients suffering from acute bacterial infections. Endogenous serum levels of G-CSF and GM-CSF, granulocyte-macrophage colony-forming cell (GM-CFC) concentrations, and differential counts were determined for the peripheral blood of 57 patients with clinically apparent bacterial infections (26 males and 31 females aged 16 to 89 years) and 18 healthy controls (8 males and 10 females aged 23 to 84 years). Patients were selected for acute-phase protein and at least two additional clinical signs reflecting a bacterial infection. Patients showed significantly higher numbers of myeloid progenitor cells than controls (median, 68 versus 26 GM-CFC/ml; P < or = 0.01). G-CSF but not GM-CSF levels were found to be elevated (> or = 50 to 863 pg/ml). In the acute stage of infection, progenitor and cytokine levels were not influenced by gender, differences in therapy, or localization of the infection. Progenitor and G-CSF levels were not associated with absolute neutrophil counts or C-reactive protein. However, a negative correlation between number of GM-CFC per milliliter and age (R = -0.47; P < or = 0.001) and an inverse relationship between the incidence of high GM-CFC concentrations and elevated G-CSF levels (phi = -0.34; P < or = 0.01) were found. Combining both parameters into a cytokine-progenitor pattern, we observed a highly significant age-dependent response of myelopoiesis to inflammation (P < or = 0.001). Younger patients had high progenitor counts (> 75 GM-CFC/ml) associated with G-CSF levels below 50 pg/ml, whereas for the older patients, the reverse pattern was predominant. The results indicate that the age-dependent myelopoietic response to acute bacterial infections is characterized by an inverse relationship between progenitor cells and G-CSF. The observed cytokine-progenitor patterns could have implications for therapy with G-CSF and the prognosis of infectious diseases.

Adolescent↗
PubMed1994

Haemopoietic cell renewal in radiation fields.

Space flight activities are inevitably associated with a chronic exposure of astronauts to a complex mixture of ionising radiation. Although no acute radiation consequences are to be expected as a rule, the possibility of Solar Particle Events (SPE) associated with relatively high doses of radiation (1 or more Gray) cannot be excluded. It is the responsibility of physicians in charge of the health of astronauts to evaluate before, during and after space flight activities the functional status of haemopoietic cell renewal. Chronic low level exposure of dogs indicate that daily gamma-exposure doses below about 2 cGy are tolerated for several years as far as blood cell concentrations are concerned. However, the stem cell pool may be severely affected. The maintenance of sufficient blood cell counts is possible only through increased cell production to compensate for the radiation inflicted excess cell loss. This behaviour of haemopoietic cell renewal during chronic low level exposure can be simulated by bioengineering models of granulocytopoiesis. It is possible to define a "turbulence region" for cell loss rates, below which an prolonged adaptation to increased radiation fields can be expected to be tolerated. On the basis of these experimental results, it is recommended to develop new biological indicators to monitor haemopoietic cell renewal at the level of the stem cell pool using blood stem cells in addition to the determination of cytokine concentrations in the serum (and other novel approaches). To prepare for unexpected haemopoietic effects during prolonged space missions, research should be increased to modify the radiation sensitivity of haemopoietic stem cells (for instance by the application of certain regulatory molecules). In addition, a "blood stem cell bank" might be established for the autologous storage of stem cells and for use in space activities keeping them in a radiation protected container.

Aerospace Medicine↗
PubMed1994

Hematologic effects of recombinant human interleukin-6 in dogs exposed to a total-body radiation dose of 2.4 Gy.

The hematologic effects of recombinant human interleukin-6 (rhIL-6) were studied in dogs exposed to a total-body irradiation (TBI) of 2.4 Gy. IL-6 was administered over a period of 14 days at a daily dose of 18 micrograms/kg by single subcutaneous injection. Treatment was started 1 day after TBI. The data obtained for the different hematologic parameters of the irradiated IL-6-treated dogs were compared with the data obtained from dogs who received TBI of 2.4 Gy and were treated with the carrier (control). No clear influence of IL-6 treatment on the pattern of recovery of lymphocytes could be detected in comparison to the irradiated control animals. The thrombocyte counts in the period from day 1 to 16 after TBI were similar for both groups of dogs, showing a sharp decrease in counts between days 6 and 12 with a stabilization thereafter at approximately 30 x 10(3)/microL. In three of the four IL-6-treated dogs, however, thrombocyte counts increased at day 18 after the beginning of treatment. This increase occurred 7 days earlier than in the controls. In two of the three dogs showing an accelerated recovery of platelet counts, however, treatment with IL-6 caused a strong decrease in the erythrocyte counts associated with a prolonged depression in reticulocyte concentration. There was no influence on the recovery of blood granulocytes. In one of the animals responding with an accelerated thrombocyte recovery, IL-6 had no adverse effect on erythropoiesis. However, IL-6 forced the recovery of blood granulocytes in the period beyond day 10 after TBI. Another animal showed no influence of IL-6 on thrombocyte recovery but a strong depressive effect on erythrocyte and reticulocyte counts. The results show that for standardized conditions of radiation-induced bone marrow damage, the pattern of response to IL-6 in different hematopoietic lineages may show considerable variations between individuals, in contrast to what has been observed in irradiated animals treated with granulocyte-macrophage or granulocyte colony-stimulating factor (GM- or G-CSF).

Animals↗
PubMed1994

Cytotoxic immigration of granulocytes into megakaryocytes as a late consequence of irradiation.

The immigration of neutrophilic granulocytes into megakaryocytes was studied in the bone marrow of normal and X-irradiated beagles under various exposure conditions. Two groups of dogs received homogeneous total-body irradiation. One group received a dose of 1.6 Gy and the other received a dose of 2.4 Gy (midline tissue). A third group was irradiated from the left side of the body only. This exposure resulted in an inhomogeneous total-body irradiation (entrance dose 3.8 Gy, exit dose 0.9 Gy). A fourth group of animals received partial-body irradiation with a dose of 11.7 Gy delivered to the anterior two-thirds of the body, thereby subjecting about 70% of the hemopoietic marrow to irradiation. Dogs of a fifth group remained unexposed to irradiation and served as controls. The marrow was analyzed in sections of the ribs approximately 1 year after irradiation. The total number of megakaryocytes in one section was evaluated. The number of megakaryocytes showing granulocytes in their cytoplasm was determined and expressed as a percentage. This phenomenon can be explained as cytotoxic immigration of granulocytes into megakaryocytes. It was observed in approximately 1-2% of the megakaryocytes in the marrow of normal dogs. One year after irradiation the value increased to 10-26%. It was observed that neutrophilic granulocytes penetrated only into the large mature megakaryocytes in which the nuclei were mostly pyknotic. This phenomenon may be considered as a late effect of irradiation.

Animals↗
PubMed1993

Radioprotective effect of N-acetylcysteine on granulocyte/macrophage colony-forming cells of human bone marrow.

N-Acetylcysteine, known as a radical scavenger, was examined for its influence on the radiotolerance of progenitor cells of granulocytopoiesis. Added before and after irradiation in a dose of 2 mg/ml to suspension cultures of non-adherent low-density human bone marrow cells N-acetylcysteine (AcCys) clearly improved the survival. The D0 value of the survival curve for granulocyte/macrophage colony-forming cells increased by a factor of 1.56 as compared to non-treated control suspensions. The improvement of radiation tolerance is probably not only based on the radical scavenger properties (radioprotective component) of AcCys, but also on the support of repair processes.

Acetylcysteine↗
PubMed1993

The effect of recombinant human stem cell factor and basic fibroblast growth factor on the in vitro radiosensitivity of CD34+ hematopoietic progenitors from human umbilical cord blood.

Human umbilical cord blood (CB) cells selected by immunomagnetic beads for expression of the CD34 antigen were irradiated with increasing doses of x-rays (72 cGy/min). Clonogenic survival of the hematopoietic progenitors, including mixed colony-forming cells (Mix-CFC), erythroid burst-forming units (BFU-E), and granulocyte-macrophage colony-forming cells (GM-CFC), was determined in methylcellulose cultures containing placenta conditioned medium (PCM) and erythropoietin (Epo). Exponential survival curves were fitted to the data of all the colonies, resulting in D0 = 95 cGy for Mix-CFC, 136 cGy for BFU-E, and 136 cGy for GM-CFC. Additionally, the radiosensitivity of CD34+ cells was studied employing cultures containing either recombinant human stem cell factor (rhSCF) or basic fibroblast growth factor (b-FGF) in combination with PCM and Epo. It was found that the colony-forming efficiency (CFE) of non-irradiated CD34+ cells of 5.5% (range 1.4 to 14.4%) did not increase after the addition of SCF or b-FGF to the culture. The radiation response characteristics showed, however, that in the presence of SCF, the D0 value and the extrapolation number n increased significantly. This suggests the stimulation of what operationally is termed "recovery from potentially lethal damage." In contrast, no response modifying effect could be seen for b-FGF.

Antigens, CD↗
PubMed1993

Effects of total-body irradiation on bone marrow erythroid burst-forming units (BFU-E) and hemopoietic regeneration in dogs.

The acute and long-term effects of total-body X irradiation (TBI) on early erythroid progenitors, burst-forming units (BFU-E), in the bone marrow of beagles were studied for midline tissue doses of 1.6 and 2.4 Gy. After both radiation doses the initial reduction in the concentration of BFU-E was greater than that found for the granulocyte-macrophage progenitor cells (GM-CFC) and thus was in general agreement with the higher in vitro radiosensitivity of BFU-E compared to GM-CFC. After TBI with 1.6 Gy the GM-CFC and BFU-E returned to their normal levels within 2-4 weeks without showing long-term radiation effects. In contrast, after TBI with 2.4 Gy the concentrations of GM-CFC and BFU-E remained below the pretreatment levels up to 1 year after exposure. For a given midline tissue dose, the extent of the long-term effect of radiation on the BFU-E in a certain bone marrow site seems to be dependent on the local radiation dose in the respective bone marrow space. The minor radiation effects observed in the erythrocyte concentration in the peripheral blood, the hematocrit, and the hemoglobin concentration point to the enormous compensatory capacity of the more mature erythropoietic transit population to increase the proliferative capacity upon demand.

Animals↗