Residual radiation effect in the murine hematopoietic stem cell compartment

Stem cells surviving radiation injury may carry defects which contribute to long-term effects. The ratio of 125-iododeoxyuridine (IUdR) uptake into spleens of lethally irradiated recipient mice between day 3 and day 5 after cell transfusion revealed reduced proliferative ability (PF) of spleen seeding cells in parallel with reduced CFU-S content of donors throughout the study period of one year after 5 Gy gamma irradiation. Additional data aided in evaluating possible mechanisms of PF reduction. Within the range of the graft sizes used, PF was independent of the numbers of cells or CFU-S transfused. Radiation-induced increase in loss of label between days 3 and 5 and prolonged doubling time of proliferating cells indicated enhancement of cell maturation and increase in mitotic cycle time. Increased IUdR uptake per transfused CFU-S suggested extra divisions of transit cells due to insufficiency in the stem cell compartment. It is concluded that persisting defects in surviving stem cells interfere in a complex way with cell proliferation in the hemopoietic system.     

Possibility of using hematopoietic stem cells in relation to their generation age

A hypothesis of the use of hemopoietic stem cells with a view of satisfying the demand for mature cells depending on their generation age predicts that CFUs that survived after repeated treatment with hydroxyurea should have a greater capacity for self-renewal. It has been demonstrated that after repeated administrations of hydroxyurea according to the scheme devised by the authors of the hypothesis (3-4 times) and as a result of a more prolonged treatment (6 times, every other 12 or 15 h), the capacity of the survived hemopoietic stem cells for self maintenance was not only lower than normal but commonly significantly decreased. The generation-age hypothesis of the use of hemopoietic stem cells thus remains badly needing experimental support.     

Residual radiation injury exhibited in long-term bone marrow cultures

Residual radiation injury was demonstrated in long-term primary cultures of mouse bone marrow. Control cultures underwent three phases of hematopoietic activity as distinguished by initial establishment, steady high (plateau) production of granulocytes, and gradual decline. Irradiation with 50, 300, or 550 rads, given at the end of the initial phase, did not prevent any culture flasks from entering the plateau phase. However, actual production levels and the time they were maintained varied inversely with the radiation dose so that the accumulated postradiation cell production corresponded to an exponential dose-response relationship at any time after treatment. The accumulated cell productions were found to be similar in all groups when expressed by the number of stem cell doublings necessary to produce them. The findings cannot be explained by reproductive cell death and are consistent with the notion of a limited division capacity in hematopoietic stem cells.     

Postirradiation change in the radiosensitivity of rats in relation to the preliminary radiation dose in the cutaneous form of radiation injury

The experimental animals were exposed two times to soft 17kV X-radiation. Post-irradiation changes in radiosensitivity were shown to depend upon dose of preliminary irradiation (10, 18 and 25 Gy). The state of radiosensitive tissues was studied and a comparison was made of a residual damage curve with a change in the proliferative activity of dividing tissue elements during 30 days after irradiation.     

HAPO促进放射损伤小鼠的造血重建

目的 明确人促血液血管细胞生成素 (HAPO)对骨髓抑制小鼠的造血重建作用。方法 研究HAPO、G-CSF对骨髓抑制小鼠的促造血作用,以700 cGy 137Csγ射线全身照射的Balb/c小鼠为模型,观察照射后小鼠的生存率;检查血常规;计数内源性脾结节;计数骨髓细胞数;采用半固体培养基进行集落培养检测骨髓细胞的高增殖潜能;取小鼠骨髓细胞接种于96孔培养板,分别在照射前或照射后加HAPO、G-CSF培养72hr,MTT方法测定活细胞数;取小鼠骨髓细胞,分别在照射后加HAPO,培养3周后观察各组小鼠骨髓细胞的生长情况。结果 HAPO、G-CSF均可明显提高放射后的小鼠的生存率;使内源性的脾集落增加。照射后的各组小鼠外周血白细胞变化较为明显,HAPO组白细胞恢复快于PBS组,也可高于G-CSF组。各组小鼠骨髓细胞数虽然14天时G-CSF组最为明显,但32天时HAPO组骨髓细胞数超过G-CSF组,至42天时基本恢复正常;而G-CSF组在32天、42天时骨髓细胞数仍低于正常值。在7天、14天、32天时取各组小鼠骨髓细胞高增殖潜能检测试验,HAPO组生成的GEMM-CFU数均最多。在照射前与HAPO、G-CSF孵育的骨髓细胞,HAPO组活细胞数量比对照组明显增高,而G-CSF组与对照组无明显差异。骨髓细胞被照射后培养72hr时,MTT测定显示不同剂量HAPO、G-CSF均能促进放射后骨髓细胞的增殖。骨髓细胞被照射后继续培养3周,HAPO组均有造血岛生成,细胞sca-1、CD31呈阳性,周围CD31阳性的内皮细胞增多。而PBS组则未出现造血岛,基质细胞中极少有CD31阳性细胞的内皮细胞,未发现sca-1阳性细胞。结论 体内、外实验表明,人促血液血管细胞生成素HAPO对放射损伤的Balb/c小鼠有明显的促造血重建作用,提高小鼠的生存率,促进其造血干细胞的增殖与生长。     

Sensitivity to radiation and recovery of hematopoietic stem cells

A function is proposed to approximate the fraction of active hematopoietic stem cells that remain after a time following irradiation by X rays. The parameters in the function are determined by minimizing the root mean square (rms) deviations of the logarithms of the function from the logarithms of the experimentally measured stem cell fractions for mice. The rms deviation obtained is 10%. The zero time limit of the function depends exponentially on the dose decaying with a D0 of 0.43 Gy in contrast to the value 0.9 Gy often quoted. This value 0.43 is shown to be consistent with an LD50 of 5.86 Gy, an average of the values previously reported by Bateman et al. [Radiology 79, 1008-1014 (1962)]. No displacement of the exponential to the right is apparent.     

Thermoregulation during exercise in relation to sex and age

The thermoregulatory responses to 1 h exercise of 14 male (age range 18--65 year) and 7 female (age range 18--46 year) athletes and 4 (3 male and 1 female) non-athletic subjects have been investigated in a moderate environment (Tdb = 21 degrees C, Twb = 15 degrees C and rh less than 50%) and analysed in relation to age, sex, and maximum aerobic power output (VO2max). The maximal sweat loss (Msw max) under the given conditions was closely related (r = + 0.90) to VO2max and for a given relative work load (%VO2max), rectal (Tre) and mean skin (Tsk) temperatures was the same in all subjects. Sweat loss (Msw) was linearly related to total heat production (H) and to peripheral tissue heat conductance (K) and if expressed in relative terms (%Mswmax) was linearly related to Tre. For a given Tre relative sweat rate was identical in the groups studied. From these results it would seem that during exercise Tre rises to meet the requirements of heat dissipation by establishing a thermal gradient from core to skin and stimulating sweating in proportion to maximal capacity of the system. Thus provided the thermal responses to work were standardised using the appropriate physiological variables, there was no evidence to be found for differences in thermoregulatory function which could be ascribed to sex or age.     

Sister-chromatid exchange in childhood in relation to age and sex

Small children have been found to have a lower SCE/cell than adults and in recent reports females have had higher SCEs/cell than males. We here describe the relationship between SCE/cell and age and sex in 46 girls and 39 boys with an age range of 1.4-19.2 years and 2.6-18.7 years, respectively. For the calculation a transformation y = (sum SCE)1/2 + (sum SCE + 1)1/2 was used. The best fit to our material was represented by the equation y = b0 + b1 X log age. A common slope (b1) could be used for the boys and girls. This slope was significantly different from zero (P less than 0.0005). The levels of the regression lines for the two sexes were different (P = 0.0006). The girls had a 0.55-0.7 higher SCE/cell than the boys, depending on age. The following equations were found: Girls: y = 22.49 + 6.53 X log age. Boys: y = 21.11 + 6.53 X log age. By this model 43% of the variation in y could be explained. As a consequence of the result it is absolutely essential, when planning studies of children, to use age-matched groups to decrease the variability of the test system.     

C3 polymorphism in relation to age.

The C3 phenotype distribution was investigated in different age-groups among 2,078 voluntary blood donors between the ages of 20 and 65 years, in a group of unrelated babies and in a group of old healthy persons. A continuous increase in the C3F gene frequency with age was found among the blood donors varying from 0.1780 in the youngest age group (babies: 0.1585) to 0.2516 at the age of 50-55 years followed by a continuous decrease to a level of 0.1700 among the eldest donors (01718 among the old persons). In the age group 45-49 years the C3 distribution differed significantly from that in the adjoining age-groups (C3F = 0.1619). It is believed that the variations are brought about by selection of the blood donor population and a balanced polymorphism for the C3 system, possibly due to differences in the biological efficiency of the C3 variants in the complement sequence.     

Cytokeratin 19 expression in human gastrointestinal mucosa during human prenatal development and in gastrointestinal tumours: relation to cell proliferation

Cytokeratin (CK) immunohistochemistry revealed changes in the CK19 immunoreactivity in human gastrointestinal epithelium during embryonic and fetal development. These changes were particularly marked in the jejunum and ileum. CK19 immunoreactivity was strong up to the 11th week of pregnancy, but was absent between weeks 12 and 17, and reappeared weakly from week 18 to week 24. This temporal pattern correlated with that of cell proliferation investigated by immunohistochemical detection of proliferating cell nuclear antigen. Marked CK expression was associated with a low proliferative rate and vice versa. To test whether these results were relevant to the assessment of intestinal metaplasia and the risk of malignant transformation with poor cell differentiation, adenomas and adenocarcinomas of the colon, intestinal metaplasia of the stomach, and two types of gastric carcinoma were also examined by CK19 immunohistochemistry. Substantial CK19 immunoreactivity was found in well-differentiated cancers and low-grade dysplasias with low cell proliferation, whereas only weak CK19 immunoreactivity was found in poorly differentiated carcinomas and high-grade dysplasias with a high proliferation rate.     

Altruistic cell suicide in relation to radiation hormesis

The high radiosensitivity to killing of undifferentiated primordial cells (Bergonié and Tribondeau 1906) can be described as a manifestation of the suicide of injured cells for the benefit of an organism as a whole if their suicide stimulates proliferation of healthy cells to replace them, resulting in complete elimination of injury. This process is called cell-replacement repair, to distinguish it from DNA repair which is rarely complete. 'Cell suicide', 'programmed death' and 'apoptosis' are terms used for the same type of active cell death. Cell suicide is not always altruistic. Altruistic suicide in Drosophila, mice, humans, plants, and E. coli is reviewed in this paper to illustrate its widely different facets. The hypothesis that in animals, radiation hormesis results from altruistic cell suicide is proposed. This hypothesis can explain the hormetic effect of low doses of radiation on the immune system in mice. In contrast, in plants, radiation hormesis seems to be mainly due to non-altruistic cell death. HORMESIS--'the stimulating effect of small doses of substances which in larger doses are inhibitory' (British Medical Dictionary, Caxton Publ. Co., 1961).