Isomeric fluorescence sensors for wide range detection of ionizing radiations

In order to achieve a wider range of ionizing radiations detection,novel fluorescence sensing materials have been developed that utilize the fluorescence enhancement phenomenon caused by the intramolecular photoinduced electron transfer(PET)effect.Two perylene diimide isomers PDI-P and PDI-B were designed and synthesized,and their molecular structures were characterized by high-resolution Fourier transform mass spectrometry(HRMS),nuclear magnetic resonance hydrogen and carbon spectroscopy(~1H and~(13)C NMR).The interaction between ionizing radiation and fluorescent molecules was simulated by HCl titration.The results show that combining PDIs and HCl can improve fluorescence through the retro-PET process.Despite the similarities in chemical structures,the fluorescent enhancement multiple of PDI-B with aromatic amine as electron donor is much higher than that of PDI-P with alkyl amine.In the direct irradiation experiments of ionizing radiation,the emission enhancement multiples of PDI-P and PDI-B are 2.01 and 45.4,respectively.Furthermore,density functional theory(DFT)and time-dependent density functional theory(TDDFT)calculations indicate that the HOMO and HOMO-1 energy ranges of PDI-P and PDI-B are 0.54 e V and 1.13 e V,respectively.A wider energy range has a stronger driving force on electrons,which is conducive to fluorescence quenching.Both femtosecond transient absorption spectroscopy(fs-TAS)and transient fluorescence spectroscopy(TFS)tests show that PDI-B has shorter charge separation lifetime and higher electron transfer rate constant.Although both isomers can significantly reduce LOD during PET process,PDI-B with aromatic amine has a wider detection range of 0.118—240 Gy due to its larger emission enhancement,which is a leap of three orders of magnitude.It breaks through the detection range of gamma radiation reported in existing studies,and provides theoretical support for the further study of sensitive and effective new materials for ionizing radiation detection.

3D-printed engineered bacteria-laden gelatin/sodium alginate composite hydrogels for biological detection of ionizing radiation

Nuclear safety is a global growing concern,where ionizing radiation(IR)is a major injury factor resulting in serious damage to organisms.The detection of IR is usually conducted with physical dosimeters;however,biological IR detection methods are deficient.Here,a living composite hydrogel consisting of engineered bacteria and gelatin/sodium alginate was 3D-printed for the biological detection of IR.Three strains of PrecA::egfp gene circuit-containing engineered Escherichia coli were constructed with IR-dependent fluorescence,and the DH5αstrain was finally selected due to its highest radiation response and fluorescence.Engineered bacteria were loaded in a series of gelatin/sodium alginate matrix hydrogels with different rheology,3D printability and bacterial applicability.A high-gelatin-content hydrogel containing 10%gelatin/1.25%sodium alginatewas optimal.The optimal living composite hydrogelwas 3D-printedwith the special bioink,which reported significant green fluorescence underγ-ray radiation.The living composite hydrogel provides a biological strategy for the detection of environmental ionizing radiation.

Aurora A Kinase Plays a Key Role in Mitosis Skip during Senescence Induced by Ionizing Radiation

Objective To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation(IR).Methods Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237(MLN)and/or p21 depletion by small interfering RNA(si RNA).Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator(FUCCI)system combined with histone H3 phosphorylation at Ser10(p S10 H3)detection.Senescence was assessed using senescence-associated-β-galactosidase(SA-β-Gal),Ki67,andγH2AX staining.Protein expression levels were determined using western blotting.Results Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment.The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells,ultimately leading to senescence in G1.During this process,the p53/p21 pathway is hyperactivated.Accompanying p21 accumulation,Aurora A kinase levels declined sharply.MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.Conclusion Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation,leading to senescence via mitotic skipping.

Protective effects of ferulic acid against ionizing radiation-induced oxidative damage in rat lens through activating Nrf2 signal pathway

AIM: To examine the protection of ferulic acid(FA) against ionizing radiation(IR)-induced lens injury in rats, as well as the underlying mechanisms.METHODS: FA(50 mg/kg) was administered to rats for 4 consecutive days before they were given 10 Gy γ-radiation, as well as for 3 consecutive days afterward. Two weeks after radiation, the eye tissues were collected. Histological alterations were evaluated by hematoxylineosin staining. Enzyme linked immunosorbent assay(ELISA) was utilized to assess the activities of glutathione reductase(GR) and superoxide dismutase(SOD), as well as the levels of glutathione(GSH) and malondialdehyde(MDA) in the lenses. The protein and m RNA levels of Bcl-2, caspase-3, Bax, heme oxygenase-1(HO-1), and glutamatecysteine ligase catalytic subunit(GCLC) were quantified using Western blot and quantitative reverse transcription polymerase chain reaction, respectively. With nuclear extracts, the nuclear factor erythroid-2 related factor(Nrf2) protein expressions in the nuclei were also measured.RESULTS: Rats exposed to IR showed lens histological alterations which could be alleviated by FA. FA treatment reversed apoptosis-related markers in IR-induced lens, as evidenced by lower levels of Bax and caspase-3 and higher level of Bcl-2. Furthermore, IR induced oxidative damage manifested by decreased GSH level, increased MDA level, and decreased SOD and GR activities. FA boosted nuclear translocation of Nrf2 and increased the expressions of HO-1 and GCLC to inhibit oxidative stress, as evidenced by an increase in GSH, a decrease in MDA, and an increase in GR and SOD activities.CONCLUSION: FA may work well in preventing and treating IR-induced cataract through promoting the Nrf2 signal pathway to attenuate oxidative damage and cell apoptosis.

Combination of genistein with ionizing radiation on andro-gen-independent prostate cancer cells

Aim: To study the effect of the combined use of genistein and ionizing radiation (IR) on prostate DU145 cancer cells. Methods: DU145, an androgen-independent human prostate cancer cell line, was used in the experiment. Clonogenic assay was used to compare the survival of DU145 cells after treatments with genistein alone and in combination with graded IR. Apoptosis was assayed by DNA ladder and TUNEL stain. Cell cycle alterations were observed by flow cytometry and related protein expressions by immunoblotting. Results: Clonogenic assay demonstrated that genistein, even at low to medium concentrations, enhanced the radiosensitivity of DU145 cells. Twenty-four hours after treatment with IR and/or genistein, apoptosis was mainly seen with genistein at high concentrations and was minimally related to IR. At 72 h, apoptosis also occurred in treatment with lower concentration of genistein, especially when combined with IR. While both IR and genistein led to G2/M cell cycle arrest, combination of them further increased the DU145 cells at G2/M phase. This Gz/M arrest was largely maintained at 72 h, accompanied by increasing apoptosis and hyperdiploid cell population. Cell-cycle related protein analysis disclosed biphasic changes in cyclin B1 and less dramatically cdc-2, but stably elevated p21cipl levels with increasing genistein concentrations. Conclusion: Genistein enhanced the radiosensitivity of DU145 prostate cancer cells. The mechanisms might be involved in the increased apoptosis, prolonged cell cycle arrest and impaired damage repair.

Effect of Ionizing Radiation on the Expression of p16, CyclinDI and CDK4 in Mouse Thymocytes and Splenocytes

Objective To investigate the effect of ionizing radiation on the expression of p16, CyclinDl, and CDK4 in mouse thymocytes and splenocytes. Methods Fluorescent staining and flow cytometry analysis were employed for the measurement of protein expression. Results In time course experiments, it was found that the expression of p16 protein was significantly increased at 8, 24, and 48 h for thymocytes (P<0.05, P<0.01, and P<0.05, respectively) and at 24 h for splenocytes (P<0.05) after whole body irradiation (WBI) with 2.0 Gy X-rays. However, the expression of CDK4 protein was significantly decreased from 8 h to 24 h for thymocytes (P<0.05,P<0.01) and from 8 h to 72 h for splenocytes (P<0.05-P<0.01). In dose effect experiments, it was found that the expression of p16 protein in thymocytes and splenocytes was significantly increased at 24 h after WBI with 1.0, 2.0, and 4.0 Gy (P<0.05-P<0.01), whereas the expression of CDK4 protein was significantly decreased with 2.0Gy for thymocytes (P<0.05) and 0.5-6.0 Gy for splenocytes (P<0.05-P<0.01). Results also showed that the expression of CyclinDl protein decreased markedly in both thymocytes and splenocytes after exposure. Conclusion The results indicate that the expression of p 16 protein in thymocytes and splenocytes can be induced by ionizing radiation, and the p16-CyclinD1/CDK4 pathway may play an important role for G1 arrest of thymocytes induced by X-rays.

Inhibition of Ciliogenesis Enhances the Cellular Sensitivity to Temozolomide and Ionizing Radiation in Human Glioblastoma Cells

Objective To investigate the function of primary cilia in regulating the cellular response to temozolomide(TMZ)and ionizing radiation(IR)in glioblastoma(GBM).Methods GBM cells were treated with TMZ or X-ray/carbon ion.The primary cilia were examined by immunostaining with Arl13 b andγ-tubulin,and the cellular resistance ability was measured by cell viability assay or survival fraction assay.Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride,the autophagy was measured by acridine orange staining assay.The DNA damage repair ability was estimated by the kinetic curve ofγH2 AX foci,and the DNAdependent protein kinase(DNA-PK)activation was detected by immunostaining assay.Results Primary cilia were frequently preserved in GBM,and the induction of ciliogenesis decreased cell proliferation.TMZ and IR promoted ciliogenesis in dose-and time-dependent manners,and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR.The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair.The interference of ciliogenesis reduced DNA-PK activation,and the knockdown of DNA-PK led to cilium formation and elongation.Conclusion Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.

Identification of Two Novel Mitochondrial DNA Deletions Induced by Ionizing Radiation

Abstract Objective We identify ionizing radiation-induced mitochondrial DNA （mtDNA） deletions in human lymphocytes and their distribution in normal populations. Methods Long-range polymerase chain reactions （PCR） using two pairs of primers specific for the human mitochondrial genome were used to analyze the lymphoblastoid cell line following exposure to 10 Gy 6~Co y-rays. Limited-condition PCR, cloning and sequencing techniques were applied to verify the mtDNA deletions detected with long-range PCR. Human peripheral blood samples were irradiated with 0, 2 and 6 Gy ^60Co y-rays, and real-time PCR analysis was performed to validate the mtDNA deletions. In order to know the distribution of mtDNA deletions in normal population, 222 healthy Chinese adults were also investigated. Results Two mtDNA deletions, a 7455-bp deletion （nt475-nt7929 in heavy strand） and a 9225-bp deletion （nt7714 -nt369 in heavy strand）, occurring between two 8-bp direct repeats, were identified in lymphoblastoid cells using long-range PCR, limited-condition PCR and sequencing. These results were also observed for ^60Co y-rays irradiated human peripheral blood cells. Conclusion Two novel mtDNA deletions, a 7455-bp deletion and a 9225-bp deletion, were induced by ionizing radiation. The rate of the mtDNA deletions within a normal population was related to the donors＇ age, but was independent of gender.

p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis

Objective To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest.Methods Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation.Depletion of p21 was carried out by employing the siR NA technique.Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28,an M-phase marker.Senescence was assessed by senescenceassociated-β-galactosidase（SA-β-gal） staining combined with Ki67 staining,a cell proliferation marker.Results Accompanying increased p21,the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays.Furthermore,these irradiated cells were blocked at the G2 phase followed by cellular senescence.Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases,as well as the high expression of histone H3 phosphorylated at Ser28.Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells.However,cells with serious DNA damage failed to undergo cytokinesis,leading to the accumulation of multinucleated cells.Conclusion Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation.Downregulation of p21 by siR NA resulted in G2-arrested cells entering into mitosis with serious DNA damage.This is the first report on elucidating the role of p21 in the bypass of mitosis.

An investigation of ionizing radiation damage in different SiGe processes

Different SiGe processes and device designs are the critical influences of ionizing radiation damage. Based on the different ionizing radiation damage in SiGe HBTs fabricated by Huajie and an IBM SiGe process, quantitatively numerical simulation of ionizing radiation damage was carried out to explicate the distribution of radiation-induced charges buildup in KT9041 and IBM SiGe HBTs. The sensitive areas of the EB-spacer and isolation oxide of KT9041 are much larger than those of the IBM SiGe HBT, and the distribution of charge buildup in KT9041 is several orders of magnitude greater than that of the IBM SiGe HBT. The result suggests that the simulations are consistent with the experiment, and indicates that the geometry of the EB-spacer, the area of the Si/SiO2 interface and the isolation structure could be contributing to the different ionizing radiation damage.

Ionizing Radiation-Induced RPL23a Reduction Regulates Apoptosis via RPL11-MDM2-p53 Pathway in Mouse Spermatogonia

Objective The expression patterns of ribosomal large subunit protein 23 a(RPL23 a)in mouse testes and GC-1 cells were analyzed to investigate the potential relationship between RPL23 a expression and spermatogonia apoptosis upon exposure to X-ray.Methods Male mice and GC-1 cells were irradiated with X-ray,terminal dUTP nick end-labelling(TUNEL)was performed to detect apoptotic spermatogonia in vivo.Apoptotic rate and cell cycle phase of GC-1 cells were analyzed with flow cytometry.Protein interactions were detected by Immunoprecipitation and protein localization as studied by immunofluorescence.Immunoblotting and real-time PCR were applied to analyze to protein and gene expression.Results Ionizing radiation(IR)increased spermatogonia apoptosis,the expression of RPL11,MDM2 and p53,and decreased RPL23 a expression in mice spermatogonia in vivo and in vitro.RPL23 a knockdown weakened the interaction between RPL23 a and RPL11,leading to p53 accumulation.Moreover,knockdown and IR decreased RPL23 a that induces spermatogonia apoptosis via RPL23 a-RPL11-MDM2-p53 pathway in GC-1 cells.Conclusion These results suggested that IR reduced RPL23 a expression,leading to weakened the RPL23 a-RPL11 interactions,which may have activated p53,resulting in spermatogonia apoptosis.These results provide insights into environmental and clinical risks of radiotherapy following exposure to IR in male fertility.The graphical abstract was available in the web of www.besjournal.com.

Ionizing radiation effect on single event upset sensitivity of ferroelectric random access memory

The impact of ionizing radiation effect on single event upset（SEU） sensitivity of ferroelectric random access memory（FRAM） is studied in this work. The test specimens were firstly subjected to ^60Co γ-ray and then the SEU evaluation was conducted using ^209Bi ions. As a result of TID-induced fatigue-like and imprint-like phenomena of the ferroelectric material, the SEU cross sections of the post-irradiated devices shift substantially. Different trends of SEU cross section with elevated dose were also found, depending on whether the same or complementary test pattern was employed during the TID exposure and the SEU measurement.

A novel approach for the prevention of ionizing radiation-induced bone loss using a designer multifunctional cerium oxide nanozyme

The disability,mortality and costs due to ionizing radiation(IR)-induced osteoporotic bone fractures are sub-stantial and no effective therapy exists.Ionizing radiation increases cellular oxidative damage,causing an imbalance in bone turnover that is primarily driven via heightened activity of the bone-resorbing osteoclast.We demonstrate that rats exposed to sublethal levels of IR develop fragile,osteoporotic bone.At reactive surface sites,cerium ions have the ability to easily undergo redox cycling:drastically adjusting their electronic con-figurations and versatile catalytic activities.These properties make cerium oxide nanomaterials fascinating.We show that an engineered artificial nanozyme composed of cerium oxide,and designed to possess a higher fraction of trivalent(Ce^(3+))surface sites,mitigates the IR-induced loss in bone area,bone architecture,and strength.These investigations also demonstrate that our nanozyme furnishes several mechanistic avenues of protection and selectively targets highly damaging reactive oxygen species,protecting the rats against IR-induced DNA damage,cellular senescence,and elevated osteoclastic activity in vitro and in vivo.Further,we reveal that our nanozyme is a previously unreported key regulator of osteoclast formation derived from macrophages while also directly targeting bone progenitor cells,favoring new bone formation despite its exposure to harmful levels of IR in vitro.These findings open a new approach for the specific prevention of IR-induced bone loss using synthesis-mediated designer multifunctional nanomaterials.

Identification of differential gene expression profiles of radioresistant lung cancer cell line established by fractionated ionizing radiation in vitro

Background Radiotherapy plays a critical role in the management of non-small cell lung cancer （NSCLC）. This study was conducted to identify gene expression profiles of acquired radioresistant NSCLC cell line established by fractionated ionizing radiation （FIR） by cDNA microarray. Methods The human lung adenocarcinoma cell line Anip973 was treated with high energy X-ray to receive 60 Gy in 4 Gy fractions. The radiosensitivity of Anip973R and its parental line were measured by clonogenic assay. Gene expression profiles of Anip973R and its parental line were analyzed using cDNA microarray consisting of 21 522 human genes. Identified partly different expressive genes were validated by quantitative reverse transcription-polymerase chain reaction （Q-RT-PCR）. Results Fifty-nine upregulated and 43 downregulated genes were identified to radio-resistant Anip973R. Up-regulated genes were associated with DNA damage repair （DDB2）, extracellular matrix （LOX）, cell adhesion （CDH2）, and apoptosis （CRYAB）. Down-regulated genes were associated with angiogenesis （GBP-1）, immune response （CD83）, and calcium signaling pathway （TNNC1）. Subsequent validation of selected eleven genes （CD24, DDB2, IGFBP3, LOX, CDH2, CRYAB, PROCR, ANXA1 DCN, GBP-1 and CD83） by Q-RT-PCR was consistent with microarray analysis. Conclusions Fractionated ionizing radiation can lead to the development of radiation resistance. Altered gene profiles of radioresistant cell line may provide new insights into mechanisms underlying clinical radioresistance for NSCLC.

Synergistic effect of ozonation and ionizing radiation for PVA decomposition

Ozonation and ionizing radiation are both advanced oxidation processes（AOPs） without chemical addition and secondary pollution. Also, the two processes＇ efficiency is determined by different p H conditions, which creates more possibilities for their combination. Importantly,the combined process of ozonation and ionizing radiation could be suitable for treating wastewaters with extreme p H values, i.e., textile wastewater. To find synergistic effects, the combined process of ozonation and ionizing radiation mineralization was investigated for degradation of polyvinyl alcohol（PVA） at different p H levels. A synergistic effect was found at initial p H in the range 3.0–9.4. When the initial p H was 3.0, the combined process of ozonation and ionizing radiation gave a PVA mineralization degree of 17%. This was 2.7 times the sum achieved by the two individual processes, and factors of 2.1 and 1.7 were achieved at initial p H of7.0 and 9.4, respectively. The combined process of ozonation and ionizing radiation was demonstrated to be a feasible strategy for treatment of PVA-containing wastewater.

TGF-β/Akt/Smad signaling regulates ionizing radiation-induced epithelial-mesenchymal transition in acquired radioresistant lung cancer cells

Objective:To define the properties of lung cancer cells that resisted conventionally fractionated radiation exposure.Methods:Acquired radioresistant lung cancer cell line A549 was constructed by X-ray irradiation with a clinical conventional fraction dose of 2 Gy daily during 30 fractions.Cell morphology,molecular markers,migration capacity and invasion potential were evaluated by the microscope,Western blot,immunofluorescence,wound healing test and transwell chamber assay,respectively.Results:Radioresistant A549 cells shifted from an epithelial to a mesenchymal morphology,termed as epithelial-mesenchymal transition(EMT),and was accompanied by decreased expressions of epithelial markers(F=4.568,P<0.05)and increased expression of mesenchymal markers(F=4.270,P<0.05),greater migratory and invasive capabilities(t=6.386,5.644,P<0.05).The expression of TGF-β,and phosphorylated levels of Akt and Smad3 were also enhanced(F=6.496,4.685,3.370,P<0.05).Furthermore,the EMT phenotype induced by radiation could be reversed through inhibition of TGF-β,Akt or Smad3,indicating a functional relationship be-tween them.Conclusions:EMT mediates acquired radioresistance of lung cancer cells induced by IR with clinical parameters,and the crosstalk mode of TGF-β/Akt/Smad signaling plays a critical regulatory role in this process.

Nuclear DNA damages generated by reactive oxygen molecules (ROS) under oxidative stress and their relevance to human cancers, including ionizing radiation-induced neoplasia part II: Relation between ROS-induced DNA damages and human cancer

Oxidative stress(OS)occurs when the production of reactive oxygen species(ROS)overrides the body’s natural defence.When the cell nucleus represents the target,macromolecular damage may result in mutations.Cancer is a disease of mutations,and DNA damages that are not repaired or mis-repaired during cell proliferation are necessary but not sufficient for cancer development.A role of ROS for cancer initiation depends on the likelihood of interaction between reactive electrophilic molecules and nuclear DNA.As described in part one of this presentation,the physico-chemical properties of the ROS involved in OS and of the ensuing DNA lesions are of major importance.Current knowledge dictates that emphasis should be shifted from oxidative DNA damages of low genotoxicity towards pro-mutagenic lesions induced by reaction products of nitrogen monoxide and complex highly reactive carbonyls,e.g.from the peroxidation of lipids.Based on the determination of pro-mutagenic DNA adducts in human tissues there is compelling evidence for a causal relation between OS and cancers of the liver,colon/rectum,cervix,pancreas and stomach.However,modulation by the simultaneous presence of an ubiquitous high background of potent pro-carcinogenic DNA adducts,which are not generated by ROS should be taken into account.Ionizing radiation is established human carcinogenic agent,and generate some of the same oxidative ROS as those involved in OS.However,the cancer spectrum from whole body radiation exposure differs in some important respects from that associated with OS.The scientific support for a causal link between exposure to non-ionizing electromagnetic radiation and human cancer is judged to be insufficient.As exemplified by diabetes,a common shortcoming when assessing the role of OS in disease is the failure to distinguish between cause and effect-i.e.could the indicators of harmful oxidative stress be the result of the pathological condition in question,rather than its cause.

Nuclear DNA damages generated by reactive oxygen molecules (ROS) under oxidative stress and their relevance to human cancers, including ionizing radiation-induced neoplasia part I: Physical, chemical and molecular biology aspects

Oxidative stress(OS)occurs when the production of reactive oxygen species(ROS)overpowers the body’s natural defence,causing macromolecular damage.The role of OS in cancer initiation will depend on the likelihood of interaction between short lived ROS and nuclear DNA.For this reason,a description of the physico-chemical properties of the various ROS that have been suggested to be involved is included.DNA damages that are not repaired or mis-repaired during cell proliferation are necessary but not sufficient for cancer initiation.The characteristics of DNA pro-mutagenic lesions and their potential role in cancer induction will be assessed,while stressing quantitative aspects as well as the importance of DNA repair.A low level of a specific DNA adduct can be compensated for by its persistence and high pro-mutagenic potency.Because ionizing radiations generate some of the same oxidative ROS as those involved in OS,the cancer spectrum from whole body radiation exposure should be compared with that associated with OS.A causal link between electromagnetic radiations and human cancer lacks adequate scientific support.Current knowledge dictates that emphasis should be shifted from oxidative damages of low genotoxicity towards pro-mutagenic lesions induced by reaction products of nitrogen monoxide and complex highly reactive carbonyls,e.g.from the peroxidation of lipids.A common shortcoming when assessing the role of OS in disease is the failure to distinguish between cause and effect-i.e.could the indicators of harmful OS be the result of the pathological condition in question,rather than its cause?Further,little attention has been paid to exposure in food to some of the same ROS(e.g.reactive carbonyl compounds),as are generated endogenously by OS.Nor have the simultaneous presence of an ubiquitous high background of potent pro-carcinogenic DNA adducts which are not generated by ROS been taken into account.

Effect of ionizing radiation on liver mitochondrial respiratory functions in mice

Objective To investigate the radiation effect on mitochondria of the mouse liver in vivo. Methods Livers of BALB/c mice were squeezed out through openings cut on the upper abdomen and radiation doses were delivered only to the livers. Radiation effects on the structure and function of liver mitochondria were evaluated from both respiratory control ratio (RCR) and ADP/O (adenosine 5' diphosphate/oxygen) ratio supported by two substrates, succinate and glutamate/malate mixtures.Results The data showed that both state 3 and state 4 respiratory rates were significantly decreased concomitantly with the increase of radiation dose up to 20 Gy. Succinate supported, but not glutamate/malate supported, respiratory control ratio, was also decreased with the increase of radiation dose. ADP/O ratios measured from the support of both succinate and glutamate/malate were not changed by γ radiation. This differential radiation damage indicated that respiratory control ratio was more vulnerable to radiation than oxidative phosphorylation.Conclusions Although the functional integrity of ATP synthetic machinery of the mitochondria was not perturbed by ionizing radiation under 20 Gy, the structural integrity of mitochondrial membrane might be affected by ionizing radiation at a dose dependent manner.

DELAYED REPAIR OF DNA DAMAGE BY IONIZING RADIATION IN PEDIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS AND JUVENILE RHEUMATOID

We have a single cell assay (SCA) to study repair of primarily single-stranded DNA breaks after in vitro ionizing radiation in children with systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (RA), progressive systemic sclerosis(PSS),and dermatomyositis. Patients with SLE, JRA, and PSS had significantly greater damage after 150 rads and 30 minutes incubation than did controls as assessed by comet length migration of damaged DNA. The average comet length in SLE was 42μm,in JRA was 40μm,and in PSS was 36μm, each of which was significantly greater than controls with an aver age comet length of 18μm (P<0.001,<0.001,and,CO.005 respectively).Patients with dermatomyositis (DMY) had an average comet length of 22 μm, which was similar to controls. In addition,the DNA damage was not repaired in as many cells from patients with autoimmune diseases. By 30 minutes after irradiation,64% of control PBL had re turned to a normal configuration. In contrast, only 18% of SLE PBL, 15% of JRA PBL,6% of PSS PBL returned to normal configuration (P<0.005);in dermatomyositis, 50%of the cells had completely repaired their DNA, which was similar to controls.These studies indicate that DNA repair is defective in patients with SLE,JRA, and PSS.Understanding this DNA repair defect may provide a new diagnostic tool and also aid in understanding the pathogenesis of these disorders.