BACKGROUND: The main manifestations of radiation pneumonitis are injury of alveolar epithelial and endothelial cells, abnormal expression of cytokines, abnormal proliferation of fibroblasts and synthesis of fibrous matrix. The occurrence of radiation pneumonitis is associated with multiplecytokine level abnormality. These cytokines can also be used as bio-markers to predict the occurrence of radiation pneumonitis. This study was to evaluate the correlation between the change of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1), intercellular adhesion molecules 1 (ICAM-1) and interleukin-17A (IL-17A) before and after radiotherapy and radiation pneumonitis for local advanced non-small cell lung cancer (NSCLC) patients with concurrent chemoradiotherapy. METHODS: NSCLC patients (68 cases) were treated with concurrent radiotherapy and chemotherapy, every patient's normal tissue were controlled with a same radation dose. 68 local advanced NSCLC patients with concurrent chemoradiotherapy were detected the levels of Ape1/Ref-1, ICAM-1 and IL-17A in serum by ELISA before radiotherapy and in the 14th week after radiotherapy. Acute and advanced radiation pulmonary injury was graded according to Radiation Therapy Oncology Group/European Organization For Research and Treatment (RTOG/EORTC) diagnostic and grading criteria. Grade 2 or more radiation pneumonitis was taken as the main end point. RESULTS: Eighteen cases out of 68 developed radiation pneumonitis, 50 of 68 cases have no radiation pneumonia development. There was no significant change of Ape1/Ref-1 levels before and after radiotherapy in radiation pneumonitis group (P>0.05). There was no significant change of Ape1/Ref-1 concentration in serum after radiotherapy between radiation pneumonitis group and non-radiation pneumonitis group (P>0.05). Compared with before radiotherapy, upregulation degree of ICAM-1 levels in radiation pneumonitis group was significantly higher than that in non- radiation pneumonitis group (P<0.05). There was no significant change of IL-17A concentration before and after radiotherapy in radiation pneumonitis group, but after radiotherapy IL-17A concentration in serum were remarkably higher than that in non-radiation pneumonitis group (P<0.05). Correlation analysis found that the change of ICAM-1 before and after radiotherapy has no obvious correlation with the incidence of radiation pneumonitis, and IL-17A change has obvious correlation with the incidence of radiation pneumonitis. CONCLUSIONS On the basis of strictly controlling radiation dose on normal tissue, IL-17A in serum could be the predictive factors of radiation pneumonitis for local advanced NSCLC patients with concurrent chemoradiotherapy.
Aged ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; radiotherapy ; Chemoradiotherapy ; adverse effects ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; blood ; Female ; Humans ; Intercellular Adhesion Molecule-1 ; blood ; Interleukin-17 ; blood ; Male ; Middle Aged ; Radiation Pneumonitis ; blood ; etiology

Inevitable human exposure to ionizing radiation from man-made sources has been increased with the proceeding of human civilization and consequently public concerns focus on the possible risk to human health. Moreover, Fukushima nuclear power plant accidents after the 2011 East-Japan earthquake and tsunami has brought the great fear and anxiety for the exposure of radiation at low levels, even much lower levels similar to natural background. Health effects of low dose radiation less than 100 mSv have been debated whether they are beneficial or detrimental because sample sizes were not large enough to allow epidemiological detection of excess effects and there was lack of consistency among the available experimental data. We have reviewed an extensive literature on the low dose radiation effects in both radiation biology and epidemiology, and highlighted some of the controversies therein. This article could provide a reasonable view of utilizing radiation for human life and responding to the public questions about radiation risk. In addition, it suggests the necessity of integrated studies of radiobiology and epidemiology at the national level in order to collect more systematic and profound information about health effects of low dose radiation.
DNA Damage/drug effects ; Environmental Exposure ; Humans ; Leukemia/epidemiology/etiology ; Neoplasms, Radiation-Induced/epidemiology ; *Radiation Dosage ; Radiation Tolerance ; *Radiation, Ionizing ; Radioactive Hazard Release ; Risk

AIM: Radiation induces an important apoptosis response in irradiated organs. The objective of this study was to investigate the radioprotective effect of tetramethylpyrazine (TMP) on irradiated lymphocytes and discover the possible mechanism of protection. METHOD: Lymphocytes were pretreated for 12 h with TMP (25-200 μmol·L(-1)) and then exposed to 4 Gy radiation. Cell apoptosis and the signaling pathway were analyzed. RESULTS: Irradiation increased cell death, DNA fragmentation, activated caspase activation and cytochrome c translocation, downregulated B-cell lymphoma 2 (Bcl-2) and up-regulated Bcl-2-associated X protein (Bax). Pretreated with TMP significantly reversed this tendency. Several anti-apoptotic characteristics of TMP, including the ability to increase cell viability, inhibit caspase-9 activation, and upregulate Bcl-2 and down-regulate Bax in 4Gy-irradiated lymphocytes were determined. Signal pathway analysis showed TMP could translate nuclear factor-κB (NF-κB) from cytosol into the nucleus. CONCLUSION The results suggest that TMP had a radioprotective effect through the NF-κB pathway to inhibit apoptosis, and it may be an effective candidate for treating radiation diseases associated with cell apoptosis.
Apoptosis ; drug effects ; radiation effects ; Cell Line ; Cell Survival ; drug effects ; radiation effects ; DNA Fragmentation ; drug effects ; radiation effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Lymphocytes ; cytology ; drug effects ; radiation effects ; NF-kappa B ; genetics ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Pyrazines ; pharmacology ; Radiation-Protective Agents ; pharmacology ; bcl-2-Associated X Protein ; genetics ; metabolism

Radiation and drug resistance remain the major challenges and causes of mortality in the treatment of locally advanced, recurrent and metastatic breast cancer. Dysregulation of phospholipase D (PLD) has been found in several human cancers and is associated with resistance to anticancer drugs. In the present study, we evaluated the effects of PLD inhibition on cell survival, cell death and DNA damage after exposure to ionizing radiation (IR). Combined IR treatment and PLD inhibition led to an increase in the radiation-induced apoptosis of MDA-MB-231 metastatic breast cancer cells. The selective inhibition of PLD1 and PLD2 led to a significant decrease in the IR-induced colony formation of breast cancer cells. Moreover, PLD inhibition suppressed the radiation-induced activation of extracellular signal-regulated kinase and enhanced the radiation-stimulated phosphorylation of the mitogen-activated protein kinases p38 and c-Jun N-terminal kinase. Furthermore, PLD inhibition, in combination with radiation, was very effective at inducing DNA damage, when compared with radiation alone. Taken together, these results suggest that PLD may be a useful target molecule for the enhancement of the radiotherapy effect.
Breast Neoplasms/*drug therapy/*enzymology/pathology ; Cell Death/drug effects/radiation effects ; Cell Line, Tumor ; Cell Proliferation/drug effects/radiation effects ; DNA Damage ; Enzyme Activation/drug effects/radiation effects ; Enzyme Inhibitors/*pharmacology/*therapeutic use ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Humans ; JNK Mitogen-Activated Protein Kinases/metabolism ; Phospholipase D/*antagonists & inhibitors/metabolism ; Radiation Tolerance/*drug effects ; Radiation, Ionizing ; p38 Mitogen-Activated Protein Kinases/metabolism

OBJECTIVETo study the protective effect of an extract of Guipi Pill () against radiation-induced damage.

METHODSA total of 100 Kunming mice were randomly divided into normal group, model group, positive drug group (treated with radioprotective agent "523", 5 mg/kg at 24 h before irradiation) and two treatment groups, with 20 mice in each group. The extract of water extraction-alcohol precipitation (WAP) from Guipi Pill were administered orally to the mice in the two treatment groups at the dose of 500 and 1,000 mg/kg, respectively, for 6 days prior to whole body radiation (8 Gy). Fifty mice with 10 in each group were used to observe the survival rate 30 days after radiation. The other 50 mice with 10 in each group were sacrificed on day 10 after radiation (6 Gy) in order to take blood, liver and unilateral femur.

RESULTSPretreatment prior to irradiation with WAP resulted in a significantly higher 30-day survival rate of mice after exposure to a potentially lethal dose of 8-Gy radiation. WAP could significantly increase the total white blood cell count and DNA content of bone marrow, and it also increased the activity of various antioxidant enzymes, such as superoxide dismutase, catalase, total antioxidant capacity and glutathione peroxidase in liver tissue of mice, which were reduced by radiation treatment. Maleic dialdehyde level and bone marrow micronucleus rate were significantly reduced by WAP, which were increased after 6-Gy radiation.

CONCLUSIONWAP of Guipi Pill could increase the 30-day survival rate and the antioxidant capacity as well as protect bone marrow in mice. WAP of Guipi Pill is an effective radioprotective agent.

Animals ; Antioxidants ; metabolism ; Bone Marrow ; pathology ; Chemical Precipitation ; DNA ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Leukocyte Count ; Liver ; metabolism ; pathology ; radiation effects ; Male ; Mice ; Micronuclei, Chromosome-Defective ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Protective Agents ; pharmacology ; therapeutic use ; Radiation Injuries, Experimental ; blood ; drug therapy ; prevention & control ; Survival Analysis ; Water

This study is to investigate the effect and mechanism of puerarin on DNA damage of HaCaT cells induced by UVB. Puerarin pre-treated cells were irradiated with UVB at 30 mJ x cm(-2). Twenty four hours after irradiation, DNA damage was detected by comet assay, ceramide was measured by thin layer chromatography and gas chromatography, intracellular free calcium ion was analyzed by flow cytometry, the phosphorylation level of p38 protein was examined by Western blotting method. Levels of DNA damage, ceramide, free calcium ion and p-p38 protein were elevated in UVB model cells. Contrary to the model group, all indicators above were reduced in all groups pre-treated by puerarin. Puerarin restrains the ceramide accumulation to block downstream p38 MAPK pathway and calcium ion rising, therefore reduces DNA damage in HaCaT cells induced by UVB.
Calcium ; metabolism ; Cell Line ; Ceramides ; metabolism ; DNA Damage ; drug effects ; radiation effects ; Down-Regulation ; Humans ; Isoflavones ; pharmacology ; Keratinocytes ; cytology ; metabolism ; Phosphorylation ; Signal Transduction ; drug effects ; Ultraviolet Rays ; adverse effects ; p38 Mitogen-Activated Protein Kinases ; metabolism

DNA-PKcs, the catalytic subunit of DNA-dependent protein kinase (DNA-PK), plays an important role in the nonhomologous end-joining (NHEJ) pathway of DNA double-strand breaks (DSBs) repair. To investigate the effects of DNA-PKcs down-regulation on cell growth and sensitization to low dose radiation (LDR), we transfected DNA-PKcs siRNA into human mammary epithelia cells MCF10F, then, detected the proliferation curve of the cells and the expression of protiens in DNA repair pathways. The results showed that DNA-PKcs gene silencing, induced by the transfection of DNA-PKcs siRNA could suppress significantly the cell proliferation and inhibit the expression of the DNA repair proteins, such as Ku80, ATM and P53 after 50 cGy 137Cs gamma-irradiation.The results suggested that DNA-PKcs gene silencing could increase the sensitivity of human breast epithelial cells to the LDR, which might be relative with the decrease of the proteins.
Breast ; cytology ; Cell Line ; DNA Repair ; drug effects ; radiation effects ; DNA-Activated Protein Kinase ; genetics ; Dose-Response Relationship, Radiation ; Epithelial Cells ; metabolism ; radiation effects ; Gene Silencing ; Humans ; Nuclear Proteins ; genetics ; RNA, Small Interfering ; genetics ; Transfection

Echinacea (E.) purpurea herb is commonly known as the purple coneflower, red sunflower and rudbeckia. In this paper, we report the curative efficacy of an Echinacea extract in gamma-irradiated mice. E. purpurea was given to male mice that were divided into five groups (control, treated, irradiated, treated before irradiation & treated after irradiation) at a dose of 30 mg/kg body weight for 2 weeks before and after irradiation with 3 Gy of gamma-rays. The results reflected the detrimental reduction effects of gamma-rays on peripheral blood hemoglobin and the levels of red blood cells, differential white blood cells, and bone marrow cells. The thiobarbituric acid-reactive substances (TBARs) level, Superoxide dismutase (SOD) and glutathione peroxidase (GSPx) activities and DNA fragmentation were also investigated. FT-Raman spectroscopy was used to explore the structural changes in liver tissues. Significant changes were observed in the microenvironment of the major constituents, including tyrosine and protein secondary structures. E. purpurea administration significantly ameliorated all estimated parameters. The radio-protection effectiveness was similar to the radio-recovery curativeness in comparison to the control group in most of the tested parameters. The radio-protection efficiency was greater than the radio-recovery in hemoglobin level during the first two weeks, in lymphoid cell count and TBARs level at the fourth week and in SOD activity during the first two weeks, as compared to the levels of these parameters in the control group.
Animals ; Antioxidants/isolation & purification/*pharmacology ; Blood Cell Count ; DNA Fragmentation/drug effects ; Echinacea/*chemistry ; Erythrocytes/drug effects/radiation effects ; *Gamma Rays ; Glutathione Peroxidase/metabolism ; Leukocytes/drug effects/radiation effects ; Lipid Peroxidation/drug effects ; Liver/*drug effects/enzymology/radiation effects ; Male ; Mice ; *Phytotherapy ; Plant Extracts/*pharmacology ; Radiation-Protective Agents/isolation & purification/pharmacology ; Random Allocation ; Superoxide Dismutase/metabolism

Equol, an isoflavonoid metabolite produced from the dietary isoflavone daidzein by the gut microflora in mammals, has been found to protect not only against ultraviolet (UV) radiation-induced cutaneous inflammation and photoimmune suppression, but also have antiphotocarcinogenic properties in mice. Because the state of DNA damage has been correlated with suppression of the immune system and photocarcinogenesis, we have therefore examined the potential of equol to offer protection from solar-simulated UV (SSUV) radiation-induced DNA damage in hairless mice by the immunohistochemical approach using monoclonal antibody specific for cyclobutane pyrimidine dimers (CPDs; H3 antibody). Topical application of 20 micrometer equol lotion, which was applied both before and after SSUV significantly reduced the number of CPDs. This reduction was evident immediately after SSUV exposure, at 1 h after exposure, and at 24 h after exposure, revealing 54%, 50%, and 26% reduction in CPDs, respectively. When the same concentration was applied for 5 consecutive days after SSUV exposure, there was no significant difference in the reduction of CPDs immediately after SSUV irradiation or at 1 hour afterwards, but there were significant reductions of 23% and 42% at 24 and 48 h after SSUV exposure, respectively. Despite apparently reducing the number of CPDs post-SSUV, topically applied equol did not appear to increase the rate of dimer removal. To conclude, equol applied topically prior to SSUV irradiation offers protection against CPD formation in hairless mice, possibly by acting as a suncreen and thus inhibiting DNA photodamage.
Administration, Topical ; Animals ; DNA/drug effects/radiation effects ; *DNA Damage ; Female ; Immunohistochemistry ; Isoflavones/*pharmacology ; Mice ; Mice, Inbred HRS ; Pyrimidine Dimers/metabolism ; Skin/drug effects/metabolism/*radiation effects ; Sunlight/adverse effects ; Ultraviolet Rays/*adverse effects

AIMTo investigate the survival rate and the level of HaCaT cells damage with ultraviolet B (UVB) radiation at various doses, and observe the protective effects of ginsenoside Rg1 and Rb1 in vitro.

METHODSMTT assay was employed to analyze the cell survival rate after UVB radiation of 30, 60, 90 and 120 mJ x cm(-2). The damage of nucleolus and the protective effects of ginsenoside Rg1 and Rb1 were scanned by Hoechst 33258 staining and single cell gel electrophoresis assay (SCGE).

RESULTSIt was found that the cell survival rate decreased gradually and the damage of nucleolus aggravated as the radiation dose increased from 30 mJ x cm(-2) to 120 mJ x cm(-2). At the dose of 20 microg x mL(1-), obvious protective effect of ginsenoside Rg1 and Rb1 can be observed against UVB radiation-induced HaCaT cells growth inhibition and nucleolus damage.

CONCLUSIONUVB radiation inhibits HaCaT human keratinocytes growth and ginsenoside Rg1 and Rb1 can relief the damage.

Apoptosis ; drug effects ; radiation effects ; Cell Line ; Cell Survival ; drug effects ; radiation effects ; DNA Damage ; drug effects ; radiation effects ; Dose-Response Relationship, Radiation ; Ginsenosides ; isolation & purification ; pharmacology ; Humans ; Keratinocytes ; cytology ; drug effects ; radiation effects ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Protective Agents ; isolation & purification ; pharmacology ; Ultraviolet Rays ; adverse effects