Persistent subclinical inflammation among A-bomb survivors

PURPOSE: To investigate the associations between inflammation tests and radiation dose in A-bomb survivors. SUBJECTS AND METHODS: Subjects were A-bomb survivors who underwent inflammation tests of leukocyte counts, neutrophil counts, erythrocyte sedimentation rate, corrected erythrocyte sedimentation rate, alpha-1 globulin, alpha-2 globulin and sialic acid between 1988 and 1992. Associations with radiation dose (DS86) were analyzed by regression analysis and heterogeneity among inflammatory diseases, anaemia at examination, or history of cancer was also tested. RESULTS: The associations with radiation dose were statistically significant for leukocyte counts (71.0mm(-3) Gy(-1), p=0.015), erythrocyte sedimentation rate (1.58 mm h(-1) Gy(-1) , p = 0.0001), corrected erythrocyte sedimentation rate (1.14mm h(-1) Gy(-1), p=0.0001), alpha-1 globulin (0.0057 g dl(-1) Gy(-1), p=0.0001), alpha-2 globulin (0.0128 g dl(-1) Gy(-1), p=0.0001), and sialic acid (1.2711 mg dl(-1) Gy(-1), p=0.0001) but not for neutrophil counts (29.9 mm(-3) Gy(-1), p=0.17). Heterogeneity was not statistically significant. Among inflammatory diseases, associations were the strongest for chronic thyroiditis and chronic liver diseases. CONCLUSIONS: This study suggests statistically significant association between inflammation in A-bomb survivors and radiation dose of during 1988-1992. The association might contribute, as an epigenetic and/or bystander effect, to development of several radiation-induced disorders.     

Persistent subclinical inflammation among A-bomb survivors

Purpose : To investigate the associations between inflammation tests and radiation dose in A-bomb survivors. Subjects and methods : Subjects were A-bomb survivors who underwent inflammation tests of leukocyte counts, neutrophil counts, erythrocyte sedimentation rate, corrected erythrocyte sedimentation rate, α -1 globulin, α -2 globulin and sialic acid between 1988 and 1992. Associations with radiation dose (DS86) were analyzed by regression analysis and heterogeneity among inflammatory diseases, anaemia at examination, or history of cancer was also tested. Results : The associations with radiation dose were statistically significant for leukocyte counts (71.0mm -3 Gy -1, p =0.015), erythrocyte sedimentation rate (1.58mm h -1 Gy -1, p =0.0001), corrected erythrocyte sedimentation rate (1.14 mm h -1 Gy -1, p =0.0001), α -1 globulin (0.0057 g dl -1 Gy -1, p =0.0001), α -2 globulin (0.0128 g dl -1 Gy -1, p =0.0001), and sialic acid (1.2711 mg dl -1 Gy -1, p =0.0001) but not for neutrophil counts (29.9mm -3 Gy -1, p =0.17). Heterogeneity was not statistically significant. Among inflammatory diseases, associations were the strongest for chronic thyroiditis and chronic liver diseases. Conclusions : This study suggests statistically significant association between inflammation in A-bomb survivors and radiation dose of during 1988-1992. The association might contribute, as an epigenetic and/or bystander effect, to development of several radiation-induced disorders.     

Memory CD4 T-cell subsets discriminated by CD43 expression level in A-bomb survivors

Purpose:?Our previous study showed that radiation exposure reduced the diversity of repertoires of memory thymus-derived cells (T cells) with cluster of differentiation (CD)- 4 among atomic-bomb (A-bomb) survivors. To evaluate the maintenance of T-cell memory within A-bomb survivors 60 years after radiation exposure, we examined functionally distinct memory CD4 T-cell subsets in the peripheral blood lymphocytes of the survivors.

Methods:?Three functionally different subsets of memory CD4 T cells were identified by differential CD43 expression levels and measured using flow cytometry. These subsets consist of functionally mature memory cells, cells weakly responsive to antigenic stimulation, and those cells functionally anergic and prone to spontaneous apoptosis.

Results:?The percentages of these subsets within the peripheral blood CD4 T-cell pool all significantly increased with age. Percentages of functionally weak and anergic subsets were also found to increase with radiation dose, fitting to a log linear model. Within the memory CD4 T-cell pool, however, there was an inverse association between radiation dose and the percentage of functionally mature memory cells.

Conclusion:?These results suggest that the steady state of T cell memory, which is regulated by cell activation and/or cell survival processes in subsets, may have been perturbed by prior radiation exposure among A-bomb survivors.     

Long-term immune effects of high-level natural radiation on Yangjiang inhabitants in China

Abstract

Purpose: Low dose radiation was found to perturb immune function or inflammatory reactions, which required further study. This study aimed to evaluate the health effects following long-term low dose radiation by detecting levels of peripheral blood lymphocyte subsets and serum cytokines of residents living in the Yangjiang High Background Radiation Area (HBRA).

Materials and methods: Flow cytometry was used to detect peripheral blood T lymphocytes and its subsets (CD4⁺ T, CD8⁺ T lymphocyte) in 100 healthy female residents selected from HBRA and a Control Area (CA), respectively. Thirty cytokines or receptors and CRP levels were measured using antibody arrays in the 40 subjects described above. Subjects were chosen based on an age and BMI match between the two groups. Cytokine expression levels were then verified using ELISA methods.

Result: In comparison to CA, CD8⁺ T lymphocyte numbers were significantly increased with cumulative dose following adjustment to age and BMI. Of the 30 selected targets, 22 indexes were measurable and inflammatory cytokines such as IFN-γ, IL-α, MCP-1, sIL-6R, EGFR, and CRP levels were observed to be significantly up-regulated with cumulative doses. ELISA results confirmed the cytokine array results and found CRP, MCP-1, and sIL-6R levels are linear with cumulative dose following adjustment to age and BMI.

Conclusion: Immune function was found to be affected in humans exposed to long-term low dose radiation. Specifically, we observed an increase in CD8⁺T lymphocyte numbers and an up-regulation of inflammatory biomarkers, including IFN-γ, MCP-1, sIL-6R, EGFR, CRP.     

Long-lasting alterations of the immune system by ionizing radiation exposure: implications for disease development among atomic bomb survivors

PURPOSE: The immune systems of the atomic-bomb (A-bomb) survivors were damaged proportionately to irradiation levels at the time of the bombing over 60 years ago. Although the survivor's immune system repaired and regenerated as the hematopoietic system has recovered, significant residual injury persists, as manifested by abnormalities in lymphoid cell composition and function. This review summarizes the long-lasting alterations in immunological functions associated with atomic-bomb irradiation, and discusses the likelihood that damaging effects of radiation on the immune system may be involved partly in disease development so frequently observed in A-bomb survivors. CONCLUSIONS: Significant immunological alterations noted include: (i) attrition of T-cell functions, as reductions in mitogen-dependent proliferation and interleukin-2 (IL-2) production; (ii) decrease in helper T-cell populations; and (iii) increase in blood inflammatory cytokine levels. These findings suggest that A-bomb radiation exposure perturbed one or more of the primary processes responsible for T-cell homeostasis and the balance between cell renewal and survival and cell death among naive and memory T cells. Such perturbed T-cell homeostasis may result in acceleration of immunological aging. Persistent inflammation, linked in some way to the perturbation of T-cell homeostasis, is key in addressing whether such noted immunological changes observed in A-bomb survivors are in fact associated with disease development.     

Comparisons of lung tumour mortality risk in the Japanese A-bomb survivors and in the Colorado Plateau uranium miners: support for the ICRP lung model

PURPOSES: To estimate the ratio of risks for exposure to radon progeny relative to low-LET radiation based on human lung cancer data, taking account of possible time and age variations in radiation-induced lung cancer risk. MATERIALS AND METHODS: Fitting two sorts of time- and age-adjusted relative risk models to a case-control dataset nested within the Colorado Plateau uranium miner cohort and to the Japanese atomic (A)-bomb survivor mortality data. RESULTS: If all A-bomb survivors are compared with the Colorado data, there are statistically significant (two-sided p < 0.05) differences between the two datasets in the pattern of the variation of relative risk with time after exposure, age at exposure and attained age. The excess relative risk decreases much faster with time, age at exposure and attained age in the Colorado uranium miners than in the Japanese A-bomb survivors. If only male A-bomb survivors are compared with the Colorado data, there are no longer statistically significant differences between the two datasets in the pattern of variation of relative risk with time after exposure, age at exposure or attained age. There are no statistically significant differences between the male and female A-bomb survivors in the speed of reduction of relative risk with time after exposure, age at exposure or attained age, although there are indications of rather faster reduction of relative risk with time and age among male survivors than among female survivors. The implicit risk conversion factor for exposure to radon progeny relative to the A-bomb radiation in the male survivors is 1.8 x 10(-2) Sv WLM(-1) (95% CI 6.1 x10(-3), 1.1 x 10(-1)) using a model with exponential adjustments for the effects of radiation for time since exposure and age at exposure, and 1.9 x 10(-2) Sv WLM(-1) (95% CI 6.2 x 10(-3), 1.6 x 10(-1)) using a model with adjustments for the effects of radiation proportional to powers of time since exposure and attained age. Estimates of the risk conversion factor calculated using variant assumptions as to the definition of lung cancer in the Colorado data, or by excluding miners for whom exposure estimates may be less reliable, are very similar. The absence of information on cigarette smoking in the Japanese A-bomb survivors, and the possibility that this may confound the time trends in radiation-induced lung cancer risk in that cohort, imply that these findings should be interpreted with caution. CONCLUSIONS: There are no statistically significant differences between the male A-bomb survivors data and the Colorado miner data in the pattern of variation of relative risk with time after exposure and age at exposure. The risk conversion factor is very close to the value suggested by the latest ICRP lung model, albeit with substantial uncertainties.     

Meta-analysis of non-tumour doses for radiation-induced cancer on the basis of dose-rate

Purpose: Quantitative analysis of cancer risk of ionising radiation as a function of dose-rate. Materials and methods: Non-tumour dose, D(nt), defined as the highest dose of radiation at which no statistically significant tumour increase was observed above the control level, was analysed as a function of dose-rate of radiation. Results: An inverse correlation was found between D(nt) and dose-rate of the radiation. D(nt) increased 20-fold with decreasing dose-rate from 1-10(-8) Gy/min for whole body irradiation with low linear energy transfer (LET) radiation. Partial body radiation also showed a dose-rate dependence with a 5- to 10-fold larger D(nt) as dose rate decreased. The dose-rate effect was also found for high LET radiation but at 10-fold lower D(nt) levels. Conclusions: The cancer risk of ionising radiation varies 1000-fold depending on the dose-rate of radiation and exposure conditions. This analysis explains the discrepancy of cancer risk between A-bomb survivors and radium dial painters.     

Henry S. Kaplan Distinguished Scientist Award 2003. The crooked shall be made straight; dose-response relationships for carcinogenesis

Estimates of radiation-induced malignancies come principally from the atomic (A)-bomb survivors and show an excess incidence of carcinomas that is linearly related to dose from about 5 cGy to 2.5 Gy. Above and below this dose range there is considerable uncertainty about the shape of the dose-response relationship. Both the International Commission of Radiation Protected (ICRP) and the National Council of Radiation Protection (NCRP) suggest that cancer risks at doses lower than those at which direct epidemiological observations are possible should be obtained by a linear extrapolation from higher doses. The demonstrated bystander effect for irradiation exaggerates the consequences of small doses of radiation and implies that a linear extrapolation from high doses would underestimate low dose risks. It is possible to make estimates of the cancer risk of diagnostic radiological procedures. Helical computed tomography in children is of particular interest since it is rapidly increasing in use and the doses involved are close to the lower limit of significance in the A-bomb survivors. For example, an abdominal computed tomographic scan in a 1-year-old child can be estimated to result in a lifetime cancer risk of about 1:1000. In the context of radiotherapy, some normal tissues receive 70 Gy, while a larger volume receives a lower dose, but still far higher than the range for which data are available from the A-bomb survivors. Data are available for the risk of radiation-induced malignancies for patients who received radiotherapy, e.g. for prostate or cervical cancer. New technologies such as intensity modulated radiation therapy could result in a doubling of radiation-induced second cancers since the technique involves a larger total-body dose due to leakage radiation and the dose distribution obtained involves a larger volume of normal tissue exposed to lower radiation doses.     

Plasma levels of interleukin-6 and C-reactive protein are associated with physical inactivity independent of obesity

It is recognized that the path from physical inactivity and obesity to lifestyle-related diseases involves low-grade inflammation, indicated by elevated plasma levels of inflammatory markers. Interestingly, contracting skeletal muscle is a major source of circulating interleukin-6 (IL-6) in response to acute exercise, but with a markedly lower response in trained subjects. As C-reactive protein (CRP) is induced by IL-6, we hypothesized that basal levels of IL-6 and CRP reflect the degree of regular physical activity when compared with other markers of inflammation associated with lifestyle-related morbidity. Fasting plasma/serum levels of IL-6, IL-18, CRP, tumur necrosis factor-alpha (TNF-alpha), soluble TNF receptor II (sTNF-RII), and adiponectin were measured in healthy non-diabetic men and women (n=84). The amount of leisure-time physical activity (LTPA) was assessed by interview. Obesity was associated with elevated insulin, C-peptide, triglycerides, low-density lipoprotein, IL-6, CRP, and adiponectin (all P<0.05). Importantly, physical inactivity was associated with elevated C-peptide (P=0.036), IL-6 (P=0.014), and CRP (P=0.007) independent of obesity, age, gender, and smoking. Furthermore, the LTPA score was inversely associated with IL-6 (P=0.017) and CRP (P=0.005), but with neither of the other markers. The results indicate that low levels of IL-6 and CRP - not IL-18, TNF-alpha, sTNF-RII, or adiponectin - reflect regular physical activity.     

Radiation treatment of acute inflammation in mice

PURPOSE: Low-dose radiotherapy (RT) has often been used effectively for the treatment of a variety of benign diseases, particularly those with acute inflammatory features. Here we report findings on radiation treatment of acute inflammation using a murine carrageenin air pouch model. MATERIALS AND METHODS: Air pouches raised on the dorsal surface of mice were injected with lambda carrageenin and were irradiated 6 h later with doses ranging from 0-5 Gy. Treatment success was evaluated at various times thereafter by volume of exudate and number of inflammatory cells, and levels of inflammation-related cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and transforming growth factor beta-1 (TGFbeta-1), and expression of inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2) and inducible heat shock protein 70 (HSP70) as determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively. RESULTS: Crude inflammatory parameters such as the amount of exudates and number of inflammatory cells remained largely unaffected by radiation or were even a slightly and transiently increased. However, the expression of iNOS was attenuated by radiation concomitant with an increase in the levels of HO-1 and HSP70. Cytokine levels varied with the radiation dose and the time point. CONCLUSIONS: Ionizing radiation, even at low doses, functionally modulates inflammatory cells. Our findings indicate possible mechanisms as to how low-dose radiation may exert anti-inflammatory effects and provide the first evidence that heat shock proteins may be involved in this response.     

Risk of breast cancer following low-dose radiation exposure.

Risk of breast cancer following radiation exposure was studied, based on surveys of tuberculosis patients who had multiple fluoroscopic examinations of the chest, mastitis patients given radiotherapy, and atomic bomb survivors. Analysis suggests that the risk is greatest for persons exposed as adolescents, although exposure at all ages carries some risk. The dose-response relationship was consistent with linearity in all studies. Direct evidence of radiation risk at doses under 0.5 Gy (50 rad) is apparent among A-bomb survivors. Fractionation does not appear to diminish risk, nor does time since exposure (even after 45 years of observation). The interval between exposure and the clinical appearance of radiogenic breast cancer may be mediated by hormonal or other age-related factors but is unrelated to dose. Age-specific absolute risk estimates for all studies are remarkably similar. The best estimate of risk among American women exposed after age 20 is 6.6 excess cancers/10(4) WY-G-Y (10(6) WY-rad).     

Direct detection of p53 -/- thymocyte appearing at an early stage of radiation-induced thymic lymphomagenesis in p53 +/- heterozygous B10 mice

PURPOSE: The appearance of tumor suppressor protein 53 (p53) -/- thymocytes at an early stage of radiation-induced lymphomagenesis was investigated in the p53 heterozygous (+/-) B10 mice following a single dose of irradiation, since most thymic lymphomas manifested the loss of the wild-type p53 allele and the loss of heterozygosity was thought to be an early event critical for radiation-induced thymic lymphomagenesis in p53 +/- mice. MATERIALS AND METHODS: The mice were exposed to a single dose (6 Gy) of irradiation to induce thymic lymphomas and, at various times after irradiation, treated with an extremely high dose (30 Gy) of whole-body irradiation to enrich p53 -/- thymocytes and, 24 h later, the remaining thymocytes were assayed for cell surface markers and p53 genotype. RESULTS: In a significant fraction of the p53 +/- mice 5 weeks after 6 Gy irradiation, there was a relative increase in the number of cluster of differentiation (CD) 4+CD8+ thymocyte subpopulation among thymocytes remaining after 30 Gy irradiation. The CD4+CD8+ double-positive (DP) thymocytes were shown to contain p53-/- cells, and the number of p53 -/- thymocytes was more than 10(5) in those individuals. CONCLUSIONS: The results clearly indicated that an extremely high dose (30 Gy) of whole-body irradiation enabled us to directly detect p53 -/- thymocytes in an abundant p53 +/- thymocyte population and that proliferative p53 -/- thymocytes develop in a CD4+CD8+ DP thymocyte subpopulation within a few weeks after a single dose (6 Gy) of irradiation.     

辐射损伤后小鼠T细胞功能亚群及其IL-4和IFN-γ的变化

目的 观察不同剂量辐射损伤后小鼠T细胞功能亚群、细胞因子IL-4和IFN-γ的变化。方法 C57BL/6j小鼠分为假照射组和辐射损伤模型组。采用⁶⁰Coγ线照射诱导辐射损伤模型。吸收剂量分别为0.7、1.4、2.8及5.6 Gy。应用细胞表面标志和细胞内因子标记结合流式细胞仪分析急性照射损伤和损伤恢复期小鼠脾CD3+、CD4+、CD8+T细胞功能亚群,以及细胞因子IL-4和IFN-γ的变化。结果 1 辐射损伤后CD3+、 CD4+及 CD8+有明显的减低,其改变幅度与受照剂量有关。2 照射后1 d, IFN-γ降低幅度明显高于IL-4,受照剂量大于2.8 Gy组,IL-4/IFN-γ比值较空白对照组明显升高。3 辐射对淋巴细胞功能亚群、细胞因子IL-4和IFN-γ的损伤在照射后25 d有不同程度的恢复,但与假照射组比较仍有明显差别。 结论 电离辐射可使淋巴细胞亚群CD3+,CD4+,CD8+、 CD4+/CD8+、细胞因子IL-4和IFN-γ发生改变,并诱发受照小鼠免疫功能低下,特别是使细胞因子IL-4和IFN-γ发生失衡,再次证实辐射损伤后小鼠脾Th1/Th2模式向Th2免疫反应漂移的现象。     

Radiation treatment of acute inflammation in mice

Purpose: Low-dose radiotherapy (RT) has often been used effectively for the treatment of a variety of benign diseases, particularly those with acute inflammatory features. Here we report findings on radiation treatment of acute inflammation using a murine carrageenin air pouch model.

Materials and methods: Air pouches raised on the dorsal surface of mice were injected with λ carrageenin and were irradiated 6 h later with doses ranging from 0 – 5 Gy. Treatment success was evaluated at various times thereafter by volume of exudate and number of inflammatory cells, and levels of inflammation-related cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and transforming growth factor beta-1 (TGFβ-1), and expression of inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2) and inducible heat shock protein 70 (HSP70) as determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively.

Results: Crude inflammatory parameters such as the amount of exudates and number of inflammatory cells remained largely unaffected by radiation or were even a slightly and transiently increased. However, the expression of iNOS was attenuated by radiation concomitant with an increase in the levels of HO-1 and HSP70. Cytokine levels varied with the radiation dose and the time point.

Conclusions: Ionizing radiation, even at low doses, functionally modulates inflammatory cells. Our findings indicate possible mechanisms as to how low-dose radiation may exert anti-inflammatory effects and provide the first evidence that heat shock proteins may be involved in this response.     

Involvement of MAPK signalling in radioadaptive response in BALB/c mice exposed to low dose ionizing radiation

To investigate low dose ionizing radiation (LDIR)-induced adaptive response in lymphocytes of BALB/c mice and to elucidate related molecular mechanisms. Mice were exposed to a priming dose (PD) of 0.1?Gy and challenge dose (CD) of 2?Gy ionizing radiation. Proliferation response to mitogen concanavalin A was assessed using ³H thymidine incorporation and carboxyfluoresceinsuccinamidylester (CFSE) dye dilution. Early activation markers were assessed by flow cytometry, cytokines by ELISA, DNA damage by comet assay and mitogen activated protein kinase (MAPK) signaling by Western blotting. Radioadaptive response was observed in lymphocytes of mice exposed to PD prior to CD of ionizing radiation in terms of DNA damage, early activation markers CD69, CD71, cytokines IL-2, IFN-γ as well as proliferation. This effect was transient and observed 24?h after CD and not after 0?h or 72?h. Hyper activation of MAPK signaling pathways in lymphocytes from LDIR-exposed mice and abrogation by ERK and p38 inhibitors suggests the involvement of MAPK signaling in radioadaptive response. Our study demonstrates that LDIR-induced transient adaptive response was due to hyper activation of MAPK signaling. Our findings contribute towards the understanding of LDIR-induced adaptive response.     

Detecting the health risks of radiation.

Radiation can cause both non-stochastic (cell-killing) effects, leading to burns, epilation, immune system damage and lens opacities, and mutational or stochastic effects due to low dose damage to single cells. If the latter are followed by clone formation or fertilization, the mutants are not recognized by the immune system, and there is no competing cause of death, cancer or leukaemia can result. These effects did not become public knowledge until after the A-bombings of Hiroshima and Nagasaki. Subsequent analysis of the data on A-bomb survivors suggests, contrary to official views, that the immune system has a complex role in the aetiology of cancer and leukaemia, and that the A-bomb survivors were unusually resistant to the harmful effects of the bombings. These findings require the re-evaluation of the effects of low-level radiation, which has increased with the growth of the nuclear industry, both civil and military.     

严重烧伤过程中大剂量补充精氨酸体内相关指标变化及对脓毒症发生的影响

目的观察大剂量补充精氨酸(arginine,Arg)对严重烧伤患者白细胞介素-16(IL-16)、白细胞介素-17(IL-17)、血清C反应蛋白(C-reactive protein,CRP)及脓毒症发生的影响。方法将2008年1月~2014年3月收治的重度以上烧伤住院患者201例,按随机数字表法分为试验组(n=112)和对照组(n=89),对照组精氨酸剂量0.1g/kg,试验组剂量0.4g/kg,观察两组患者治疗前及治疗后3、7、14d血清IL-16、IL-17、CRP变化,并统计两组脓毒症发病率。结果治疗7d后,试验组患者IL-16、IL-17、CRP较对照组显著下降(P﹤0.01);脓毒症发病率显著低于对照组(P﹤0.05)。结论大剂量Arg的补充能够降低严重烧伤患者体内炎症反应;降低脓毒症的发病率,可能是通过降低患者IL-16、IL-17、血清CRP的水平来实现的。     

还原型谷胱甘肽对小鼠放射性肺损伤的影响

目的 研究还原型谷胱甘肽(GSH)对放射性肺损伤(RILI)小鼠的作用及其损伤机制。方法 100只BALB/c小鼠随机数字表法分为健康对照组、15 Gy组、30 Gy组、15 Gy+GSH组和30 Gy+GSH组,每组20只。GSH组小鼠腹腔注射0.2 ml 240 mg/ml GSH,单纯照射组腹腔注射等体积的生理盐水作对照,建立15和30 Gy X射线的RILI模型。于照射前、照射后1、2、3周收集血样,采用ELISA法检测MMP-9、TIMP-1、IL-4和IL-6的表达量,HE染色观察病理情况,并分析小鼠的体重和免疫系统变化。结果 照射后,小鼠的脾脏指数先急速下降,下降速度随照射剂量增加而降低(F=29.84,P<0.05);1周后随照射剂增加而慢慢上升(F=13.91、4.61,P<0.05)。血清MMP-9与IL-6表达随照射剂量增加而升高(F=81.27、10.86,P<0.05),TIMP-1和IL-4相反。随照射后时间延长,MMP-9表达量先上升后下降(F=52.22,P<0.05),TIMP-1和IL-4先下降后上升(F=138.96、8.48,P<0.05),IL-6表达始终上升。结论 GSH具有抗放射性肺损伤作用,尤其在低剂量照射下更明显。     

Effects of low dose irradiation on TK6 and U937 cells: induction of p53 and its role in cell-cycle delay and the adaptive response

PURPOSE: To investigate the effect of small doses of radiation on the cell-cycle and related processes, and to determine the capacity of small doses of radiation to induce an adaptive response. MATERIALS AND METHODS: TK6, a lymphoblast cell line with wild-type p53, and U937, a monocytic leukaemia cell line with mutant, inactive, p53 were exposed to gamma ray doses ranging from 0.1 Gy to 3 Gy. Cell-cycle distributions and cyclin B1 were assessed by flow cytometry, and p53 and p21 protein levels were measured by Western blotting. Apoptosis was determined by fluorescence microscopy after staining with Hoechst 33342, and by measurement of the pre-G1 cell population by flow cytometry. Micronuclei were determined in cytokinesis-blocked cells by fluorescence microscopy. RESULTS: In TK6 cells, radiation exposure induced elevated p53 and p21 levels and delayed expression of cyclin B1. No changes in these parameters were found in U937 cells. Although both cell lines arrested in G2/M after larger doses of radiation, G2/M-arrest occurred after 0.1 Gy and 0.3 Gy in TK6 cells only. An apoptotic adaptive response was induced in both cell lines by a 0.1 Gy priming dose but an adaptive response with respect to micronuclei was observed only in U937 cells. CONCLUSIONS: The radiation adaptive response can occur in the absence of wild-type p53. A small dose of radiation may not protect cells against both apoptosis and cytogenetic damage caused by a subsequent larger dose of radiation.     

Effects of low dose irradiation on TK6 and U937 cells: induction of p53 and its role in cell-cycle delay and the adaptive response

Purpose: To investigate the effect of small doses of radiation on the cell-cycle and related processes, and to determine the capacity of small doses of radiation to induce an adaptive response. Materials and methods: TK6, a lymphoblast cell line with wild-type p53, and U937, a monocytic leukaemia cell line with mutant, inactive, p53 were exposed to gamma ray doses ranging from 0.1Gy to 3Gy. Cell-cycle distributions and cyclin B1 were assessed by flow cytometry, and p53 and p21 protein levels were measured by Western blotting. Apoptosis was determined by fluorescence microscopy after staining with Hoechst 33342, and by measurement of the pre-G1 cell population by flow cytometry. Micronuclei were determined in cytokinesis-blocked cells by fluorescence microscopy. Results: In TK6 cells, radiation exposure induced elevated p53 and p21 levels and delayed expression of cyclin B1. No changes in these parameters were found in U937 cells. Although both cell lines arrested in G2/M after larger doses of radiation, G2/M-arrest occurred after 0.1Gy and 0.3Gy in TK6 cells only. An apoptotic adaptive response was induced in both cell lines by a 0.1Gy priming dose but an adaptive response with respect to micronuclei was observed only in U937 cells. Conclusions: The radiation adaptive response can occur in the absence of wild-type p53. A small dose of radiation may not protect cells against both apoptosis and cytogenetic damage caused by a subsequent larger dose of radiation.