Enhanced activity of deoxycytidine kinase after pulsed low dose rate and single dose gamma irradiation

In both pulsed low dose rate (LDR) and single high dose radiation schedules, gemcitabine pretreatment sensitizes tumor cells to radiation. These radiosensitizing effects could be the result of decreased DNA repair. In this study, the effect of irradiation on the deoxycytidine kinase (dCK) needed for DNA repair was investigated. The activity of dCK, a deoxynucleoside analogue-activating enzyme was increased upon irradiation in both schedules. No change in dCK protein expression was observed that indicates a post-translational regulation. The benefit of this increased activity induced by irradiation should be further investigated in combination with deoxynucleoside analogues activated by this enzyme.     

Effect of continuous irradiation with a very low dose of gamma rays on life span and the immune system in SJL mice prone to B-cell lymphoma

Ionizing radiation has been shown to have dose- and dose-rate-dependent carcinogenic effects on the hematopoietic and lymphoreticular systems. We report here that continuous exposure to a low dose of gamma rays influences the course of spontaneous B-cell lymphoma in SJL mice. We studied the biological effects of 10 cGy year(-1) gamma rays on the life span of 560 4-week-old SJL/J female mice and on various parameters of the cell-mediated immune response. Life span was slightly prolonged. The mean survival was 397 days for controls and 417 days for irradiated mice that died with lymphoma (P = 0.34). In lymph nodes and spleen, lower percentages of CD4+ and CD8+ T cells were observed in irradiated mice before 32 weeks. Interestingly, the percentages of CD49+ NK cells were increased in the spleens of irradiated mice at 28 weeks (0.61 +/- 0.08% compared to 0.43 +/- 0.12% in controls, P = 0.01) and at 32 weeks (0.62 +/- 0.24% compared to 0.33 +/- 0.09%, P = 0.02), while NK cell activity remained unchanged in exposed mice. These results provide further support for the absence of harmful effects of a continuous very low dose of radiation on life span and incidence of lymphoma in SJL mice.     

Effect of low dose and moderate dose gamma irradiation on the mechanical properties of bone and soft tissue allografts

The increased use of allograft tissue for musculoskeletal repair has brought more focus to the safety of allogenic tissue and the efficacy of various sterilization techniques. Gamma irradiation is an effective method for providing terminal sterilization to biological tissue, but it is also reported to have deleterious effects on tissue mechanics in a dose-dependent manner. At irradiation ranges up to 25 kGy, a clear relationship between mechanical strength and dose has yet to be established. The aim of this study was to investigate the mechanical properties of bone and soft tissue allografts, irradiated on dry ice at a low absorbed dose (18.3–21.8 kGy) and a moderate absorbed dose (24.0–28.5 kGy), using conventional compressive and tensile testing, respectively. Bone grafts consisted of Cloward dowels and iliac crest wedges, while soft tissue grafts consisted of patellar tendons, anterior tibialis tendons, semitendinosus tendons, and fascia lata. There were no statistical differences in mechanical strength or modulus of elasticity for any graft irradiated at a low absorbed dose, compared to control groups. Also, bone allografts and two soft tissue allografts (anterior tibialis and semitendinosus tendon) that were irradiated at a moderate dose demonstrated similar strength and modulus of elasticity values to control groups. The results of this study support the use of low dose and moderate dose gamma irradiation of bone grafts. For soft tissue grafts, the results support the use of low dose irradiation.     

Response of human fibroblasts to low dose rate gamma irradiation

Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to gamma radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase in the terminal slope (D0) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury.     

The effect of low dose gamma irradiation on the differentiation and maturation of monocyte derived dendritic cells

The effects of gamma-irradiation on the differentiation of peripheral blood monocytes (PBM) into monocyte derived dendritic cells (MDC), their maturation, and subsequent ability to present antigen to T cells was studied. Undifferentiated MDC were more sensitive to gamma-irradiation induced apoptosis than mature MDC. Irradiation of immature MDC with 5 Gy of gamma-rays down regulated the expression of the costimulatory receptors CD80/CD86 and may compromise their ability to capture and present antigen. By contrast, gamma-Irradiation of mature MDC did not affect the expression of CD86/CD80, and HLA-DR. Gamma-irradiation increased the apoptosis of MDC; but did not affect the ability of mMDC to stimulate autologous MLR. T cell proliferative response in the MLR and in response to tetanus antigen was reduced when gamma-irradiated primary DC1 were used to either stimulate or present antigen to T cells.     

Interleukin-10 inhibits neutrophil phagocytic and bactericidal activity

Abstract Effective host defense against bacterial invasion is characterized by the vigorous recruitment and activation of inflammatory cells, which is dependent upon the coordinated expression of both pro- and anti-inflammatory cytokines. Interleukin-10 (IL-10) is a recently described cytokine with potent anti-inflammatory properties in vivo and in vitro. In this study we investigated whether IL-10 could directly regulate the ability of neutrophils (PMN) to phagocytose and kill bacteria. Initial studies demonstrated that human recombinant IL-10 (hrIL-10) inhibited the ability of PMN to phagocytose Escherichia coli in vitro. Inhibition of phagocytosis occurred in the absence of changes in CR1 (C3b) or Fc receptor expression, as treatment of PMN with IL-10 failed to induce significant changes in FcγIIR, FcγIIIR or CR1 cell surface expression. However, incubation of PMN with IL-10 resulted in a dose-dependent decrease in CD11b (Mac-1) expression. In addition to effects on PMN phagocytosis, hrIL-10 significantly attenuated PMN microbicidal activity, as bactericidal assays revealed that co-incubation of PMN with hrIL-10 resulted in a marked decrease in killing of phagocytosed bacteria. Furthermore, IL-10 inhibited the production of superoxide from PMA-stimulated PMN, suggesting that the detrimental effects of IL-10 on PMN microbicidal activity were due, in part, to suppression of respiratory burst. In summary, our studies indicate that IL-10 inhibits PMN-dependent phagocytosis and killing of E. coli in vitro, and suggest that this cytokine may impair effective antibacterial host defense in vivo.     

Effect of irradiation on proteins and phagocytic activity of rat blood leukocytes

The method of chromatography on DEAE-cellulose was used to study the effect of radiation (180.6 mC/kg) on the physicochemical properties of rat leukocyte proteins. The qualitative changes were noted in the protein spectrum of leukocytes which were indicative of the substantial changes in the cell proteins. A fraction was isolated which caused a 44% inhibition of the phagocytic activity of intact leukocytes in vitro.     

Changes in the number of DNA-protein cross links in spleen lymphocytes of mice exposed to low intensity low dose gamma irradiation

Levels of DNA-protein cross-links (DPC) and DNA single-strand breaks (SSB) in spleen lymphocytes were studied in mice exposed to low-intensity gamma-radiation (1.7 mGy/day) for 1, 4, 10, 20, and 30 days. The spleen mass and count of lymphocytes isolated from this organ also has been investigated. The significant increase in the DPC level as compared to the control occurred on the 10-th and 30-th days of irradiation at doses of 1.7 and 5.1 cGy, accordingly. The number of spleen lymphocytes normalized to organ mass significantly decreased on the 4-th and 30-th days of the experiment. No increase was found in levels of alkali-labile sites and SSB. In contrast, the increase in the amount of duplex form DNA was recorded on the 4-th and 30-th days of the experiment. Our indicate that DPC formation after irradiation at low doses represents some form of cellular response to the damaging agent.     

Effect of continuous irradiation on the thrombopoietic system in mice

In this paper the changes of the megakaryocyte number of the spleen and those of thrombocyte number of the peripheral blood were studied during continuous irradiation with a dose rate of 9.57 to 957 mGy/day. Beginning with a dose rate of 95.7 mGy/day the thrombocyte number of the blood and the megakaryocyte number of the spleen of irradiated animals decreased significantly. Whereas the thrombocyte number remained permanently decreased, the cell number of the megakaryocyte type is increased temporarily to a clearly higher level as compared with the controls on the 100th day of irradiation approximately. This is especially true for the middle dose rate. During this time of irradiation nucleolar hyperchromatosis as well as pycnosis were observed in many megakaryocytes.     

Effects of 10-day long exposure to gamma irradiation at low doses on bone marrow cells in mice

Effects of ten day long exposure to gamma-irradiation at low doses (mean dose rate of 1.5-2.0 m Gy/day, total dose of 15 m Gy) on hemopoietic (CFU-S) and stromal (CFU-F) progenitor cells from murine bone marrow were examined. The CFU-F content measured as in vitro fibroblastic colony number showed 1.5-4.5-fold increase. Additionally, the size of ectopic marrow transplants evaluated by counting myelokariocytes and CFU-S numbers also increased. No significant changes of CFU-S proliferation rate were found.     

Changes in the leukocyte phagocytic activity of donor blood after its UV irradiation. I. Its relation to the irradiation dose and initial level of phagocytic activity

Phagocytic activity of human mono- and granulocytes increased markedly after UV blood irradiation in the apparatus "Izolda" used in hospitals of the USSR for medical treatment. With the rise of irradiation dose the ratio of cells ingesting latex particles increased, although the average number of particles ingested per cell decreased. The integrative phagocytic index poorly depended on the irradiation dose. In patients with a low initial level of phagocytic index, after UV blood irradiation it became more pronounced than in those with the initial elevated level. The enhancement of phagocytic activity is the result of a direct UV-stimulation of cells. This stimulation not mediated by irradiated blood plasma is known to inhibit the phagocytic activity of leucocytes. A possible mechanism of phagocytic activity stimulation is discussed.     

Changes in androgen binding protein (ABP) production following continuous low dose gamma irradiation (IR) of adult rat

Continuous low dose gamma irradiation induces a progressive degeneration of germ cells with a concomittant increase in blood FSH; however, the Sertoli cell function is not too much altered since serum ABP level is normal and it is likely that the decrease of epididymal ABP content is the consequence of a reduction in seminiferous tubule fluid excretion. Obviously, spermatids seems to be involved in the regulation of Sertoli cell ABP synthesis.     

Study of genome instability using DNA fingerprinting of the offspring of male mice subjected to chronic low dose gamma irradiation

By a polymerase chain reaction with an arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F1 generation) from male parents of mice exposed to chronic low-level gamma-radiation was studied. Male BALB/c mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old offspring mice and DNA was isolated. The primer in the AP-PCR was a 20-mer oligonucleotide flanking the microsatellite locus Atp1b2 on chromosome 11 of the mouse. A comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of microsatellite-associated sequences in the genome of the offspring of the males exposed to 25 and 50 cGy. The DNA-fingerprints of the offspring of male mice exposed to chronic irradiation with the doses 10 and 25 cGy 15 days before fertilization (at the post-meiotic stage of spermatogenesis) showed an increased frequency of "non-parent bands". The results of the study point to the possibility of transmission to the offspring somatic cells of changes increasing genome instability from male parents exposed to chronic low-level radiation prior to fertilization.     

Inhibitory effects of post low dose gamma-ray irradiation on ferric-nitrilotriacetate-induced mice liver damage

We studied the effects of a single post whole-body low-dose irradiation (50 cGy of γ-ray) on mice with ferric nitrilotriacetate (Fe³⁺-NTA)-induced transient hepatopathy. As a result, low-dose irradiation accelerated the rate of recovery. Based on the changes in glutamic oxaloacetic transaminase (GOT) activities, glutamic pyruvic transaminase (GPT) activities and lipid peroxide levels, it was shown that hepatopathy was improved by low-dose irradiation 3 h after Fe³⁺-NTA administration. This may be because of the enhancement of antioxidant agents such as total glutathione (GSH + GSSG), glutathione peroxidase (GPX), glutathione reductase (GR) and γ-glutamylcysteine synthetase (γ-GCS) by low-dose irradiation. These findings suggest that low-dose irradiation relieved functional disorders at least in the livers of mice with active oxygen species related diseases.     

Effect of low doses of gamma irradiation on in vitro growth of grapevine

Shoot tips and single node explants of two rootstocks (R.99 and 3309) and two varieties (‘Helwani’ and ‘Cabernet Franc’) of grapevine cultured on DSD1 media for a period of 60 days, were irradiated with 0, 2, 5 and 7 Gy doses of gamma irradiation. Shoot length of ‘Helwani’ and ‘Cabernet Franc’ was increased by 7 Gy irradiation. The 5 Gy dose increased the number of roots in plants of the two rootstocks and ‘Helwani’. Root length of ‘Helwani’ and ‘Cabernet Franc’ at the 2 and 7 Gy doses were significantly higher than those of the non-irradiated control. A similar effect was noticed on R.99 rootstock subjected to 5 Gy. Five Gy also increased the dry weight of the R.99 rootstock, whereas 2 and 7 Gy had a similar effect on ‘Helwani’ and ‘Cabernet Franc’. Number of leaves of plants exposed to 5 and 7 Gy was increased when compared with the non-irradiated control. This revised version was published online in June 2006 with corrections to the Cover Date.