Protective Effect of Biophytum sensitivum (L.) DC on Radiation-Induced Damage in Mice

The radioprotective effect of Biophytum sensitivum methanol extract was studied using in vivo mice model . Animals were exposed to whole body gamma irradiation (6 Gy/animal) after treatment with B. sensitivum (50mg/kg b.wt.) followed by estimation of cytosolic enzymes, level of antioxidants, hematological parameters, bone marrow cellular progenitors, serum cytokine levels and spleen hematopoietic colonies. Administration of B. sensitivum could reduce the enhanced level of ALP, GPT and LPO levels in irradiated animals. B. sensitivum could significantly enhance the glutathione (GSH) content in liver and intestinal mucosa of irradiated animals. B. sensitivum treatment could enhance the Total WBC count, cellularity of bone marrow, alpha-esterase positive cells, and relative organ weight of spleen as well as thymus. The number of hematopoietic colonies on the surface of the spleen was found to be enhanced after B. sensitivum treatment. B. sensitivum treatment could also stimulate the production of cytokines such as IL-1β, IFN-γ and GM-CSF in animals exposed to whole body gamma irradiation. The present investigation suggests that the protective effect of Biophytum sensitivum on Radiation-Induced hemopoietic damage is mediated through immunomodulation as well as sequential induction of IL-1β, GM-CSF and IFN-γ.     

Effect of a hyperthermic treatment on the pluripotent haemopoietic stem cell in normal and anaemic mice

Up to now, the hyperthermic sensitivity of pluripotent haemopoietic stem cells is unknown, and the few existing data from reports in the literature are conflicting. There are two main drawbacks in the set-up of those studies: (1) only CFU-S day 9 results were presented, whereas it is questionable if this assay gives a true reflection of the pluripotent stem cell, and (2) no attention has been paid to heat effects on the seeding efficiency, i.e. the amount of stem cells which will lodge in the spleen. The present study focused on the procedural differences and compared the results of a hyperthermic treatment (60 min, 42°C) on the stem cells, assayed with the CFU-S day 9 and the CFU-S day 12 method, using the following three stem cell suspensions, all differing in their proliferative activity: bone marrow from normal mice and bone marrow and spleen cells from anaemic mice. Furthermore, we investigated the seeding efficiency before and after heat treatment. Resting stem cells, assayed with the CFU-S day 12 method, turned out to be resistant to hyperthermia as compared with the active cycling stem cells, while with the CFU-S day 9 assay the stem showed the same thermosensitivity in the two bone marrow suspensions. The active cycling stem cells do not significantly differ in thermosensitivity, in CFU-S day 9 and day 12 assays, although there is a difference between bone marrow and spleen. Hyperthermia appears to influence the seeding efficiency for spleen CFU-S; an increase of 1?73 was observed. The difference in heat sensitivity between the resting and the active cycling stem cells, assayed with both in vivo methods, however, cannot be explained by a change in seeding efficiency only. Comparing the amount of cycling cells in the three stem cell suspensions and their thermosensitivity leads to the conclusion that the differences in heat sensitivity might be fully explained by the cycling status of the stem cell.     

Modifications of CFU-S differentiation pathways by pluripoietins: influence of treatment protocols

Similar total doses of Ara-C given as a single injection or given in a fractionated protocol have reverse effects on CFU-S differentiation pathways. Whereas a single dose of 20 mg channels CFU-S towards erythropoiesis, 5 X 5 mg given at 8 or 24 hour intervals channels CFU-S to granulopoiesis and megakaryocytopoiesis. It therefore seems possible to manipulate CFU-S differentiation not only by varying the inducing agents but also by varying the protocols using the same agent. Hypotheses to explain the mechanisms of CFU-S regulation are presented.     

Residual toxicity in hematopoietic cells following a single dose of methylnitrosourea

The residual injury to the proliferation capability of hemopoietic stem cells (CFU-S) which results from their exposure to leukemogenic agents was evaluated in mice given a single leukemogenic dose of methol nitrosourea (MNU 50 mg/kg body weight, i.v.). Bone marrow cellularity, splenic weight, number of CFU-S and the proportion of cycling to noncycling CFU-S were measured in an effort to detect acute and residual injury to the CFU-S from mice given MNU 21 and 3 days earlier. Marrow cells were also transferred into lethally irradiated mice to observe the self-renewal capability of the CFU-S in the recipient spleen and bone marrow. The results of these measurements show that the CFU-S in marrow from mice given 50 mg/kg of MNU 21 days earlier still have a defective ability for self-renewal, although the total cellularity, number of CFU-S and proportion of cycling and noncycling CFU-S in the donor have returned to the normal range. The relationship of this self-renewal defect to the development of leukemia after this leukemogenic dose of MNU is not known.     

Splenic colony formation by liver cells from mouse embryos of different ages in the presence of thymocytes

Research Institute of Medical Radiology, Academy of Medical Sciences of the USSR, Obninsk. (Presented by Academician of the Academy of Medical Sciences of the USSR V. A. Nasonova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 5, pp. 464–465, May, 1990.     

CFU-S的不均一性与放射损伤效应的研究

正常(NBM)与3Gy照射(IBM)骨髓细胞形成的7～13天脾结节数量变化过程不同。NBM组: 7～9天脾结节数呈指数性增加I 9～11天呈指数性下降;11～13天再次增加。IBM组: 7～9天脾结节数增加幅度加大, 但9天后脾结节数无明显改变。NBM组：8天脾结节以红系为主, 13天脾结节以混合型为主。IBM组。8天脾结节中, 红系较对照组明显下降, 13天时与对照无明显差别。 8天CFU-S的放射敏感性高于13天CFU-S, D0值分别为1.09和1.48Gy。在8Gy全身照射后, 小鼠骨髓中8天和13天CFU-S的恢复过程大致相似。本文的实验结果表明, CFU-S的放射敏感性也是不均一的。在7～9天的CFU-S中, 可能存在一个趋向红系分化而对射线更敏感的亚群。     

IRM-2近交系小鼠对电离辐射抗性的研究

目的观察IRM-2小鼠对电离辐射的耐受性.方法分析测定了IRM-2小鼠对137Csγ射线的LD50及经4.0Gy137Csγ射线照射后不同时间外周血白细胞、骨髓有核细胞总数、骨髓细胞DNA含量和脾结节的变化,并与亲代小鼠ICR和615进行了比较.结果用不同剂量的137Csγ射线照射后,IRM-2小鼠对γ射线的LD50比ICR和615小鼠分别高1.73～1.57Gy和1.44Gy;外周血白细胞数和骨髓有核细胞总数、骨髓细胞DNA含量下降的幅度小且恢复得快;CFU-S的增加也较ICR和615小鼠明显.结论IRM-2小鼠比一般的纯系和杂交品系小鼠具有更强的辐射抗性.     

Enhanced acceptance of regenerating bone marrow of random bred newborn mice by random bred adult mice

Summary Regenerating bone marrow of newborn random bred Sabra mice (9–13 days old) was obtained by the administration of two consecutive i. p. injections of hydroxyurea (HU) (2×1000 mg/kg body wt), three days prior to collection of the marrow cells. The bone marrow of HU-treated newborn mice was assayed for CFU-S, CFU-C and plasma-clot-diffusion-chamber (PCDC) progenitor cells. A fourfold content of CFU-S was found in the regenerating bone marrow compared with that of the control marrow, while the level of CFU-C and PCDC progenitor cells was the same in treated and untreated newborn mice. In lethally irradiated adult, random bred Sabra recipient mice, transfused with regenerating bone marrow from newborn mice, the initial survival rate was greater than in irradiated animals receiving normal newborn marrow (75% as against 50%); marrow repopulation, 10–14 days after transfusion, was also greater in the former than in the latter group of animals (1.5–2×10⁶ nucleated cells per femur as compared with 0.8–2×10⁵). The bone marrow of these groups of mice was assayed for CFU-S, CFU-C and PCDC progenitor cells; with a cell inoculum of 5×10⁴ i. v., 10⁵ in vitro and 5×10⁴ per DC, respectively, pluripotent and committed stem cells were detected in the experimental group and were lacking in control recipients.Regenerating bone marrow of newborn mice was also transfused into lethally irradiated splenectomized recipients. In this experimental group there was high mortality, low marrow repopulation and lack of CFU-S (5–10×10⁴ cell inoculum).The results of this study indicate that, despite genetic differences among random bred Sabra mice, regenerating bone marrow of newborn mice takes better than normal marrow in lethally irradiated recipients. Improved marrow acceptance is possibly due to the increased content of activated CFU-S and/or pre-CFU-S in the regenerating bone marrow.Supported by a grant from Das Ministerium für Wissenschaft und Kunst, Land Niedersachsen, Federal Republic of Germany