The alteration of attractiveness of intact males mice to females chemosignals, subjected of ionizing radiation in sublethal dose

After irradiation in a dose 4 Gy female mice of CBA and C57Bl/6 (female CBA during 18-23 days, female C57Bl/6 - 4-10 days) secretes with urine volatile components (chemosignals) which possess higher, than secretes intact females, attractiveness for intact males the same strains irrespective of a genotype. When estimation relative attractiveness postradiation secretes female mice CBA and C57Bl/6 intact males prefer chemosignals singenic (genetically identical) females during 1-23 day after irradiation. Observed olfactorial reaction male mice more differ from norm. In which males prefer chemosignals of allogenic (with a strange genotype) females. This disturbances identifed as postradiation reversion attractiving males of chemosignals, dependent on the genotype of females. Typical for norm chemosignalisation at females restored for 43 days after the irradiation. The mechanism and biological advisability of this phenomenon are discussed.     

Influence of the irradiating on olfactory ability of male mice to distinguish chemo-signals of intact individuals

It is shown, that in early terms after irradiating of male mice of lines CBA and C57Bl/6 in a sublethal dose (4 Gy) in reaction of preference-avoiding lose olfactory ability to distinguish the genotype of flying secretions of female mice and to distinguish flying secretions of female mice from secretions of male mice. Irradiated male mice not only preserve, but also raise the attractiveness to chemosignals of syngenetic intact male mice.     

Mitochondrial DNA mutations in individuals occupationally exposed to ionizing radiation

Mutations in a 443-bp amplicon of the hypervariable region HVR1 of the D-loop of mitochondrial DNA (mtDNA) were quantified in DNA extracted from peripheral blood samples of 10 retired radiation workers who had accumulated external radiation doses of >0.9 Sv over the course of their working life and were compared to the levels of mutations in 10 control individuals matched for age and smoking status. The mutation rate in the 10 exposed individuals was 9.92 x 10(-5) mutations/ nucleotide, and for the controls it was 8.65 x 10(-5) mutations/ nucleotide, with a procedural error rate of 2.65 x 10(-5) mutations/nucleotide. No increase in mtDNA mutations due to radiation exposure was detectable (P = 0.640). In contrast, chromosomal translocation frequencies, a validated radiobiological technique for retrospective dosimetric purposes, were significantly elevated in the exposed individuals. This suggests that mutations identified through sequencing of mtDNA in peripheral blood lymphocytes do not represent a promising genetic marker of DNA damage after low-dose or low-dose-rate exposures to ionizing radiation. There was an increase in singleton mutations above that attributable to procedural error in both exposed and control groups that is likely to reflect age-related somatic mutation.     

Lenticular opacities in individuals exposed to ionizing radiation in infancy.

Development of lens opacities and the measures taken to avoid them have clinical relevance in the fields of oncology, radiotherapy and radiation protection. The aim of this study was to correlate the prevalence of lenticular opacities in individuals exposed to ionizing radiation in childhood with radiation dose and other possible risk factors. Between 1920 and 1959, about 16,500 children (age <18 months) with skin hemangiomas were referred to Radiumhemmet, Karolinska University Hospital, 89% of whom were treated with radiotherapy. A total of 484 exposed individuals and 89 nonexposed controls participated in an ophthalmological examination. Lens opacities were found in 357 (37%) of the 953 lenses examined in the exposed persons. In contrast, lens opacities were observed in only 35 (20%) of the 178 lenses examined in the nonexposed control individuals. It is concluded that the increased prevalence of cortical and posterior subcapsular opacities is related to previous radiotherapy. Age at examination was the strongest modifier of risk. Children exposed to a lenticular dose of 1 Gy had a 50% increased risk (odds ratio 1.50; 95% confidence interval 1.10-2.05) of developing a posterior subcapsular opacity and a 35% increased risk of a cortical opacity (odds ratio 1.35; 95% confidence interval 1. 07- 1.69).     

Lipopolysaccharide sensitized male and female juvenile brains to ionizing radiation

Radiotherapy is an effective tool in the treatment of pediatric malignancies but it is associated with adverse side effects, both short- and long-term. One common long-term side effect after cranial radiotherapy is cognitive impairment and this is, at least partly, thought to be caused by reduced hippocampal neurogenesis. Neuroinflammation and a perturbed microenvironment are thought to be important in the dysregulation of neurogenesis seen after irradiation (IR). We investigated the effects of a pre-existing, lipopolysaccharide (LPS)-induced systemic inflammation at the time of IR in both males and females. A single dose of 8 Gy to the brain of postnatal day 14 mice caused an upregulation of cytokines/chemokines (IL-1β, MIP-1β, IL-12, GM-CSF, MIP-1α, IL-17, CCL2 and KC) 6 h after IR, more so in females. Caspase-3 activity, reflecting apoptosis and possibly microglia activation, was elevated 6 h after IR. Females treated with LPS before IR showed a higher caspase-3 activity compared with males. During the chronic phase (3 months post IR), we found that LPS-induced inflammation at the time of IR aggravated the IR-induced injury in both male and female mice, as judged by reduced bromodeoxyuridine incorporation and neurogenesis (doublecortin-positive cells) in the hippocampus. At this late time point, the microglia density was increased by IR, more so in females, indicating long-term effects on the microenvironment. IR increased anxiety-related behavior in vehicle-, but not LPS-, treated animals. However, exploratory behavior was affected by IR in both vehicle- and LPS-treated mice. In conclusion, we found that LPS administration before IR of the young mouse brain aggravated the injury, as judged by reduced hippocampal neurogenesis. This supports the clinical practice to postpone radiotherapy if the patient shows signs of infection. Systemic inflammation is not always obvious, though, for example because of concurrent corticosteroid treatment, so careful monitoring of inflammation is warranted.     

Effect of ionizing radiation on the aggressive behavior of mice

Changes in the aggressiveness of mice were studied after exposure thereof to 5, 10, 30, 60 and 100 Gy radiation. With doses of 5, 10 and 30 Gy no stable effect on the aggressive behaviour of mice was observed, while doses of 60 and 100 Gy suppressed it drastically. Stress at the time of exposure can enhance the antiaggressive effect of radiation.     

c-myb Heterozygous mice are hypersensitive to 5-fluorouracil and ionizing radiation

Hypersensitivity to chemo- and radiotherapy employed during cancer treatment complicates patient management. Identifying mutations in genes that compromise tissue recovery would rationalize treatment and may spare hypersensitive patients undue tissue damage. Genes that govern stem cell homeostasis, survival, and progenitor cell maintenance are of particular interest in this regard. We used wild-type and c-myb knock-out mice as model systems to explore stem and progenitor cell numbers and sensitivity to cytotoxic damage in two radiosensitive tissue compartments, the bone marrow and colon. Because c-myb null mice are not viable, we used c-myb heterozygous mice to test for defects in stem-progenitor cell pool recovery following gamma-radiation and 5-fluorouracil treatment, showing that c-myb(+/-) mice are hypersensitive to both agents. While apoptosis is comparable in mutant and wild-type mice following radiation exposure, the crypt beds of c-myb(+/-) mice are markedly depleted of proliferating cells. Extrapolating from these data, we speculate that acute responses to cytotoxic damage in some patients may also be attributed to compromised c-myb function.     

大剂量电离辐射对小鼠肺组织的影响

目的探讨大剂量电离辐射对小鼠肺的影响。方法 60Coγ照射小鼠,HE染色观察小鼠肺组织损伤,免疫组化检测小鼠肺转化生长因子β1(TGFβ1)和细胞间粘附因子1(ICAM1)的表达。结果大剂量照射后3d,小鼠肺发生明显异常病变,TGFβ1和ICAM1表达量明显增加。结论肺内皮细胞损伤和血管内物质外漏可能是急性放射性肺损伤的早期重要事件,早期检测ICAM1有助于预测急性放射性肺损伤的发生程度。     

Effect of radiation-induced bystander chemosignals of mice on the humoral immune response in spleen and lymph nodes of intact recipients

The ability of post-radiation (4 Gy) bystander chemosignals (the volatile components of mouse urine) to distantly modulate the humoral immune response to the sheep red blood cells in the spleen and popliteal lymph nodes of intact recipients has been investigated. It was shown that the exposure of animals to chemosignals before antigen injection resulted in the decrease and increase of the immune response in the spleen and lymph nodes, respectively. When animals were exposed to chemosignals after the antigenic stimulus, an increased immune response was observed in both spleen and lymph nodes. The contribution of radiation-induced bystander signaling in the response of socially organized animals to the effect of ionizing irradiation is discussed.     

Postradiation volatile secretion of mice attractive for intact individuals

In early period after exposure to a sub-lethal dose (4 Gy) the exposed mice secreted volatile components (in their urine), which were attractive for intact individuals independently of genotype. The postradiation components were more attractive for allogene individuals than for singene ones. This reaction was different in exposed intact mice, which showed singene attractiveness of volatile secretion. Attractiveness of postradiation volatile components differed from the attractiveness of ones secreted after stress.     

The effects of ionizing radiation on the pulmonary vasculature of intact rats and isolated pulmonary endothelium

We studied the effects of ionizing radiation on the morphology of the pulmonary circulation using an in vivo rat model and an in vitro pulmonary artery endothelial cell model. Gamma radiation was given as either an acute (30 Gy) or fractionated (5 X 6 Gy) dose to one hemithorax of rats. An acute 30-Gy dose delivered resulted in a 70% decrease in pulmonary arterial perfusion, using technetium-99m microaggregated albumin (99mTc-MAA), in the irradiated lung by 2-3 weeks after irradiation. Pulmonary microradiographs, using a barium sulfate perfusion method, obtained 2-3 weeks after irradiation demonstrated widespread loss of capillary filling and segmentation of the vessels. Histologic examination demonstrated intact capillaries, suggesting that the alterations in pulmonary perfusion were at the precapillary level. Similar abnormalities in lung perfusion and morphology were found after delivery of fractionated doses of radiation, but the onset of the changes was delayed, occurring 4-6 weeks postirradiation. Using cultured pulmonary endothelial cell monolayers, cell sloughing and retraction from the surface substrate were observed within 24 h after in vitro delivery of 30 Gy. Similar findings occurred in monolayers given fractionated doses (5 X 6 Gy) of radiation 2-3 days after the final dose. The in vivo animal and in vitro endothelial cell models offer a useful means of examining the morphologic alterations involved in radiation lung vascular damage.     

Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4⁺ T, CD8⁺ T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1α, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-γ. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naïve T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose γ-radiation, which may be associated with the functional benefits observed in various experimental models.     

Radioprotective properties of eckol against ionizing radiation in mice

We have investigated the radioprotective efficacy of eckol, a component of brown seaweed Ecklonia cava, against the gamma ray-induced damage in vivo. Our results showed that eckol significantly decreased the mortality of lethally irradiated mice. The mechanisms of eckol's protection were found to include: an improvement in hematopoietic recovery, the repair of damaged DNA in immune cells and an enhancement of their proliferation, which had been severely suppressed by ionizing radiation. Thus, we propose eckol as a candidate for adjuvant therapy to alleviate radiation-induced injuries to cancer patients.