Ultraviolet radiation (UVR) is known to be highly mutagenic. What types of DNA lesions that are induced by different UVR wavelengths are still a matter of debate. UVR induces mutagenesis mostly by the formation of photoproducts and the induction of reactive oxygen species (ROS). ROS can give rise to mutations via oxidation of nucleotides in the DNA or the nucleotide pool. Oxidized nucleotides in the nucleotide pool can thereby be incorporated into the DNA during replication and ultimately give rise to mutations. MTH1 however, dephosphorylates oxidized nucleotides in the nucleotide pool, in particular 8-oxo-dGTP and 2-OH-dATP, and inhibits their incorporation into the DNA.The aim of the present study was to investigate the role of MTH1 in mutagenesis and cytogenetic damage induced by UVR in a human lymphoblastoid TK6 cell line. The clonogenic survival, mutant frequency and micronucleus frequency were measured following exposure to UVA, UVB and UVC in MTH1-knockdown and wild-type TK6 cells. As a biomarker for oxidative damage the level of intracellular and extracellular 8-oxo-dG was measured in TK6 cells exposed to UVA. The mutational spectra of UVA-induced mutations at the thymidine kinase gene in MTH1-knockdown and wild-type TK6 cells were investigated.The results show that MTH1 protects against UVA and UVB mutagenesis significantly. MTH1, however, has been shown to offer no protection against UVR-induced cytogenetic damage and is therefore suggested to mainly inhibit mutagenesis. The mutational spectra show that GC&gt;AT and AT&gt;GC transitions are the dominant mutation types in cells exposed to UVA.In conclusion, MTH1 protects TK6 cells against mutagenesis induced by longer wavelengths of UVR. This indicates that the nucleotide pool is a significant target in mutagenesis for longer wavelengths of UVR. The type of mutations induced by UVA, GC&gt;AT and AT&gt;GC, can be formed by the incorporation of 2-OH-dATP from nucleotide pool into the DNA. UVA is therefore suggested to induce mutations by induction of oxidized nucleotides such as 2-OH-dATP. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.</p>

In the first part of studies, Controlled Auto-Ignition (CAI) combustion was investigated in a Ricardo E6 single cylinder, four stroke gasoline engine. CAI combustion is achieved by employing positive valve overlap configuration in combination with various compression ratios and intake air temperature strategies. The CAI operational region is limited by engine load due to knock and partial burned boundaries. The combustion characteristics and emissions are studied in order to understand the major advantages and drawbacks of CAI combustion with positive valve overlap. The enlargement of the CAI operational region is obtained by boosting intake air and external EGR. The lean-boosted operation elevators the range of CAI combustion to the higher load region, and the use of external EGR allows the engine to operation with CAI combustion in the mid range of region between boosted and N/A CAI operational range. The results are analyzed and combustion characteristics, performance and emissions are investigated. A Ricardo Hydra single cylinder, four stroke optical gasoline engine with optical access is then experimented to investigate CAI combustion through negative valve overlap configuration and an intake heater. The effects of direct fuel injection timings spark timings and air/fuel ratio are studied by means of simultaneous incylinder heat release study and direct visualization, chemiluminescence techniques which uses full, OH radical and CHO species. Both heat release analysis and chemiluminescence results have identified the pressure of minor combustion during the NVO period. Both the charge cooling and local air/fuel ratio effects are also investigated by varying the quantity of direct air injection.

Introduktion: Systemisk Lupus Erythematosus är en prototypisk autoimmun sjukdom som gör att immunförsvarets antikroppar angriper kroppens egna vävnader, vilket leder till kronisk inflammation i kroppens organsystem. Idag finns ingen verksam behandling för Systemisk Lupus Erythematosus. Syftet med denna studie var att undersöka hur Dvitamintillskott påverkar Systemisk Lupus Erythematosus. Metod: Artiklarna hittades i databasen ”Pubmed” med sökningen ”Systemic Lupus Erythematosus and vitamin D supplementation”. Bland sökresultaten fanns sex relevanta artiklar som hade undersökt effekten av D-vitamintillskott på SLE. Resultat: Mer än hälften av patienterna i samtliga studier nådde serum 25(OH) D-nivåer som ansågs vara tillräckliga. D-vitamintillskottet minskade Th1/Th17-cellerna men ökade också Treg-celler och Th2-celler. Tre studier visade sig ha en signifikant minskning i sjukdomsaktivitet och anti-dsDNA antikroppar. Komplement C3 minskade i studie 2. Diskussion: Fem av studierna tyder på att oral administrering av D-vitamin tillskott har gett positiv inverkan på SLE. Två av de granskade studierna rapporterades inge positiv klinisk effekt hos deltagarna. Slutsats: D-vitamintillskott dämpar immunsystemet genom att öka Treg-celler och Th-2-celler men även minska Th1/Th17-celler och B-celler samt produktionen av autoantikroppar och anti-dsDNA-antikroppar. Effekten av D-vitamintillskott på komplement C3 och C4 är oklar. Det krävs dock fler studier med fler deltagarantal för att dra en slutsats om Dvitamintillskott kan användas som behandling för SLE. / Background: Systemic Lupus Erythematosus is a prototypical autoimmune disease in which antibodies attack healthy tissues in the body, causing inflammation in several organs. Aim: The aim of this literature study was to investigate the effect of Vitamin Dsupplementation on SLE. Method: The articles were searched in the database called ”Pubmed” using the search terms ”Systemic Lupus Erythematosus and Vitamin D supplementation”. Six of the articles which examined the effects of D-vitamin supplementation on SLE were relevant for this study. Result: More than half of the patients in all six studies reached sufficient serum 25(OH)D. Vitamin D-supplement reduced Th1/Th17-cells but increased Tregs-cells and Th2-cells. 3 studies showed a decrease in disease-activity and anti-dsDNA. C3 decreased in study 2. Discussion: Five studies indicated that the oral administration of vitamin-D supplementation had a positive effect on SLE. Two of the examined studies did not observe any clinical effect of the vitamin-D supplement. Conclusion: Vitamin-D supplement suppresses the immunesystem by increasing Treg cells and Th-2 cells but also reducing Th1/Th17-cells and B-cells as well as the production of autoantibodies and anti-dsDNA antibodies. The effect of vitamin D-supplement is unclear. More studies with more participants are required to determine if vitamin-D supplement can be used as a treatment for SLE.

Submitted by FERNANDA DA SILVA VON PORSTER (fdsvporster@univates.br) on 2016-08-31T19:30:52Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) 2015NathaliaGrave.pdf: 1012668 bytes, checksum: 34206baa81b06129beaa75c62787bbc4 (MD5) / Approved for entry into archive by Ana Paula Lisboa Monteiro (monteiro@univates.br) on 2016-09-05T19:29:54Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) 2015NathaliaGrave.pdf: 1012668 bytes, checksum: 34206baa81b06129beaa75c62787bbc4 (MD5) / Made available in DSpace on 2016-09-05T19:29:54Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) 2015NathaliaGrave.pdf: 1012668 bytes, checksum: 34206baa81b06129beaa75c62787bbc4 (MD5) Previous issue date: 2016-08 / Introdução: Muitos estudos tem relacionado a deficiência de vitamina D com o risco para as doenças crônicas, principalmente obesidade e dislipidemia. A vitamina D age através da ligação ao receptor de vitamina D (VDR), o qual forma heterodímeros com o receptor do retinoide X gama (RXRG). O gene GC codifica a proteína de ligação da vitamina D (DBP), a qual é responsável pelo transporte da vitamina D na corrente sanguínea. Considerando que a genética desempenha um papel importante na etiologia destas doenças, poucos estudos analisam a associação de variantes em genes da rota da vitamina D com parâmetros antropométricos e bioquímicos relacionados a estes desfechos. Objetivo: Investigar a associação entre polimorfismos de genes relacionados à rota da vitamina D, rs2228570 (gene VDR), rs2134095 (gene RXRG), rs7041 (gene GC), e parâmetros antropométricos e bioquímicos em uma amostra de adultos. Métodos: Medidas antropométricas e bioquímicas foram avaliadas em 542 indivíduos adultos de ambos os gêneros em uma amostra de base populacional. O DNA genômico foi extraído a partir de amostra de sangue e os polimorfismos foram genotipados pela reação em cadeia da polimerase (PCR) através de discriminação alélica TaqMan (Applied Biosystems, Foster City, CA). As comparações dos desfechos entre os genótipos foram feitas usando ANOVA, Kruskal-Wallis, qui-quadrado de Pearson ou teste exato de Fisher, e as interações gene-gene foram avaliadas usando modelo linear geral. Resultados: Não identificamos nenhum efeito principal dos polimorfismos nos parâmetros avaliados. No entanto, ao analisarmos as interações gene-gene, detectamos uma interação significativa entre os genes RXRG e GC sobre os níveis de colesterol LDL. Conclusões: Nossos achados evidenciaram uma interação significativa entre polimorfismos de dois genes da rota da vitamina D, rs2134095 (RXRG) e rs7041 (GC) sobre os níveis de colesterol LDL, corroborando os achados da literatura que tem consistentemente relacionado a vitamina D com o perfil lipídico. / Introduction: Many studies have related vitamin D deficiency with the risk for chronic diseases, especially obesity and dyslipidemia. Vitamin D acts by binding to the vitamin D receptor (VDR), which form heterodimers with the retinoid X receptor gamma (RXRG). The GC gene encoding the binding protein Vitamin D (BPD), which is responsible for the vitamin D transport in the bloodstream. Considering that genetics play a significant role in the etiology of these diseases, few studies have analyzed the association of variants in genes of vitamin D route anthropometric and biochemical parameters related to these outcomes. Objective: To investigate the association between gene polymorphisms related to vitamin D route, rs2228570 (VDR gene), rs2134095 (RXRG gene), rs7041 (GC gene), and anthropometric and biochemical parameters in a sample of adults. Methods: anthropometric and biochemical measures were assessed in 542 adults of both genders in a population-based sample. Genomic DNA was extracted from blood sample and polymorphisms were genotyped by polymerase chain reaction (PCR) using the TaqMan allelic discrimination (Applied Biosystems, Foster City, CA). Comparisons of outcomes between genotypes were performed using ANOVA, Kruskal-Wallis test, chi-square test or Fisher's exact test, and gene-gene interactions were assessed using general linear model. Results: We have not identified any major effect of polymorphisms in the evaluated parameters. However, when we analyze the gene-gene interactions, we detected a significant interaction between RXRG and GC genes on LDL cholesterol levels. Conclusions: Our findings showed a significant interaction between polymorphisms in two genes of vitamin D route, rs2134095 (RXRG) and rs7041 (GC) on the levels of LDL cholesterol, corroborating literature findings that have consistently related to vitamin D with the profile lipid.

O presente estudo teve como objetivo avaliar o perfil da molécula relacionada à inflamação (ICAM-1), citocinas e da atividade das NTPDases como potencial influência sobre a genotoxicicdade em trabalhadores expostos ocupacionalmente a HPA. Este estudo incluiu 45 taxistas e 40 indivíduos com atividades administrativas (não-expostos ocupacionalmente), ambos nãi fumantes. O monitoramento biológico foi realizado pela quantificação do 1-hidroxipireno (1-pireno OH) urinário. A expressão de ICAM-1 (CD54) em neutrófilos foi realizada por citometria de fluxo. O perfil de hidrólise das NTPDases em plaquetas foi determinada pelo método colorimétrico. Além disso, os níveis de malondialdeído no plasma (MDA), citoquinas inflamatórias (IL-1β, IL-6, IL-10, TNF-α e IFN-γ) e o dano ao DNA (ensaio cometa e do micronúcleo) foram também avaliados. Os resultados demonstraram que os níveis de 1-OH pireno foram significativamente aumentados nos motoristas de táxi em comparação com o grupo não exposto ocupacionamente (p <0.0001); também foi positivamente correlacionada com neutrófilos ICAM-1, níveis de MDA e biomarcadores de danos no DNA. A expressão de ICAM-1 em neutrófilos foi significativamente elevado em motoristas de táxi (p <0.05), bem como os níveis de MDA (p <0.01), sendo a última positivamente correlacionada com a % de DNA na Cauda e frequência de MN. Aumento da hidrólise de ATP e ADP forma encontrados nos taxistas. Concentrações dos marcadores pró-inflamatórios foram aumentadas e anti-inflamatórias (IL-10) diminuída no grupo exposto. Para o teste de ensaio de micronúcleos e cometa, houve aumento significativo em motoristas de táxi, inclusive depois da adição de enzimas de reparo. Correlações positivas foram encontradas entre IL-1β, IL-6, TNF-α, IFN-γ e preditores de danos no DNA (% de DNA na cauda e frequência de MN), enquanto que a IL-10 está negativamente correlacionada com os biomarcadores de lesão ao DNA. Em resumo, a exposição ocupacional à poluição do ar pode levar a anormalidade homeostática como potencial contribuição para o processo aterosclerótico. Este estudo mostrou também que a exposição crônica à poluição do ar pode causar danos no DNA relacionado com a peroxidação lipídica e processo inflamatório. / The present study aimed to evaluate the profile of inflammatory molecule (ICAM-1), cytokines and the NTPDases activity as potential influence on genotoxicity process in workers exposed occupationally to PAH. This study included 45 taxi drivers and 40 non-occupationally exposed subjects, both non smorkers. Biological monitoring was performed by quantification of urinary 1-hydroxypyrene (1-OH pyrene). The expression of ICAM-1 (CD54) in neutrophil was performed and the hydrolysis profile of the NTPDases in platelets was determined. Plasma malondialdehyde (MDA) levels, inflammatory cytokines and DNA damage (comet and micronucleus assays) were also evaluated. The results demonstrated that the 1-OH pyrene levels were significantly increased in taxi drivers (p<0.0001); were also positively correlated to neutrophil ICAM-1 expression, MDA levels and biomarkers of DNA damage. ICAM-1 expression in neutrophil was significantly elevated in taxi drivers (p<0.05), as well as MDA levels (p<0.01), being the last positively correlated with % Tail DNA and MN frequency. ATP and ADP hydrolysis was increased in taxi drivers. Pro-inflammatory markers concentrations were increased and anti-inflammatory (IL-10) was decreased in exposed group. For the comet assay and micronucleus test, increase was significant in taxi drivers, inclusive after repair enzymes. Positively correlations were found between IL-1β, IL-6, TNF-α, IFN-γ and predictors of DNA damage (%Tail DNA and MN frequency), while IL-10 is negatively correlated with the biomarkers of DNA lesion. In summary, occupational exposure to air pollution, especially to PAHs, may be related with homeostatic abnormality as potential contribute to atherosclerosis process. This study showed also that the chronic exposure to outdoor air pollution may cause DNA damage related with lipid peroxidation and inflammatory process.

O gênero Glandularia (Verbenaceae) é constituído por cerca de 80 espécies que ocorrem em regiões subtropicais e temperadas da América do Sul e América do Norte, com uma distribuição disjunta. No Sul do Brasil, encontra-se a espécie Glandularia selloi (Spreng.) Tronc., que não apresenta utilização medicinal descrita na literatura assim como não há relatos de estudos sobre a sua composição química. No entanto, a investigação do potencial químico da espécie torna-se importante como uma interessante fonte para a descoberta de novas substâncias ativas a partir de produtos naturais. O objetivo deste estudo foi investigar os principais metabólitos de Glandularia selloi nativa do Rio Grande do Sul. Para os experimentos foram coletados material na cidade de Osório, RS – Brasil, sendo posteriormente seco em temperatura ambiente, separado em raízes, caules, folhas e inflorescência, pulverizados em moinho de facas e submetido a maceração com metanol. Foram realizadas análises com CLAE-DAD, CLUE-EM visando caracterizar os extratos. Compostos obtidos através de cromatografia de coluna de sílica gel foram analisados por RMN 1H e RMN 13C. As análises permitiram identificar quatro compostos sendo eles: verbascosídeo, crisoeriol diglicosilado e diacetilado, crisoeriol diglicosilado e monoacetilado e 6-OH-β-ipolamida. Realizou-se também ensaio de citotoxicidade com extratos metanólicos de raízes, caules, folhas e inflorescência de Glandularia selloi, onde se observou efeito citotóxico em todos os extratos. / The Glandularia genus (Verbenaceae) comprises about 80 species occurring in subtropical and temperate regions of South America and North America, with a disjunct distribution. In the southern regions of Brazil, the Glandularia selloi (Spreng.) Tronc. species can be found, which has no medical uses described in literature and no reports on its chemical composition have been found either. However, investigation of the chemical potential of this species becomes important as a strategy to discover new active substances from natural products. The aim of this study was to investigate the main metabolites of a native species from Rio Grande do Sul, Glandularia selloi. Botanical samples for experiments were collected in the city of Osório, RS - Brazil, and subsequently dried separated by parts, crushed and subjected to methanol maceration. Analysis by HPLC-PDA, UPLC-MS were performed aiming to characterize the extracts. Isolated compounds obtained through column chromatography on silica gel were analyzed by 1H and 13C NMR. These analyses allowed the identification of four compounds: verbascoside, diglycosylated and diacetylated crysoeriol, diglycosylated and monoacetylated crysoeriol and 6-β-OH-hydroxyipolamiide. Further assays also were carried out to investigate the cytotoxicity of the species and it was observed that the methanolic extracts of all Glandularia selloi parts were cytotoxic species.

Even though low mass stars (< 8 solar masses) vastly outnumber high mass stars (< 8 solar masses), the more massive stars drive the chemical evolution of galaxies from which the next generation of stars and planets can form. Understanding mass loss of asymptotic giant branch stars contributes to our understanding of the chemical evolution of the galaxy, stellar populations, and star formation history. Stars with mass < 8 solar masses form planetary nebulae, while those with mass < 8 solar masses go supernova. In both cases, these stars enrich their environments with elements heavier than simple hydrogen and helium molecules. While some general info about how stars die and form planetary nebulae are known, specific details are missing due to a lack of high-resolution observations and analysis of the intermediate stages. For example, we know that mass loss in stars creates morphologically diverse planetary nebulae, but we do not know the uniformity of these processes, and therefore lack detailed models to better predict how spherically symmetric stars form asymmetric nebulae. We have selected a specific group of late-stage stars and observed them at different scales to reveal the uniformity of mass loss through different layers close to the star. This includes observing nearby masers that trace the molecular shell structure around these stars. This study revealed detailed structure that was analyzed for uniformity to place constraints on how the mass loss processes behave in models. These results will feed into our ability to create more detailed models to better predict the chemical evolution of the next generation of stars and planets.

2,2',3,5',6-pentachlorobiphenyl (PCB95) is a chiral congener of the persistent organic pollutants (POPs) family of PCBs. It has been shown that chiral PCBs can be enantioselectively transformed into hydroxylated metabolites by cytochrome P450 in animals. Previous studies in our group suggested that PCB 95 can be enantioselectively translocated and metabolized in whole poplar plants. In this work, healthy whole poplar plants were hydroponically exposed to PCB95 for 30 days. Two unknown OH-PCB95 metabolites were detected in the roots by HPLC-MS. Different chromatographic and spectrometry techniques, including HPLC-MS, NMR and GC-MS, were tried to determine the structure of the more abundant metabolite of the two. It was identified to be 4'-OH-PCB95 (4'-95) by GC-MS method. The data show that PCB95 can be transformed into at least two hydroxylated metabolites by whole poplar plants, with one of them being 4'-95. Chiral analysis of 4'-95 by HPLC-MS showed slightly more abundance of the second eluting enantiomer E2-4'-95 in the roots, suggesting that the biotransformation of PCB95 to 4'-95 is enantioselective. Comparison with animal studies shows a distinct metabolite profile in whole poplar plants.

Le radical hydroxyle (OH) représente le plus important oxydant dans la troposphère et le puits de la plus grande partie des composés à l'état de trace de l'atmosphère. Si les sources des radicaux hydroxyles sont aujourd'hui relativement bien connues, le terme 'puits' des OH, connu sous le terme de réactivité atmosphérique totale avec les radicaux OH (ou réactivité OH) (s-1), reste encore difficile à quantifier. En raison de la complexité des instruments nécessaires, peu de mesures de OH et de réactivité sont actuellement disponibles et la nouvelle méthode proposée par Sinha et al., (2008) représente une alternative prometteuse pour la quantification de la réactivité atmosphérique totale avec les radicaux hydroxyles. Cette méthode est appelée Méthode Comparative de Réactivité (CRM) et est basée sur la mesure rapide d'une molécule normalement absente de l'atmosphère (ici pyrrole, C4H5N) et qui réagit à un taux connu avec les radicaux hydroxyles produits artificiellement dans une petite cellule de réaction en verre. La comparaison des concentrations de pyrrole obtenues en présence/absence d'air ambiant, dans un champ de radicaux constant, permet de quantifier la réactivité de l'air ambiant. Cette thèse a eu pour objectif principal le développement et l'optimisation de cette méthode pour la mesure de réactivité en zone urbaine, fortement riche en monoxyde d'azote (NO), composé identifié comme produisant des artefacts de la mesure. De même, il fallait proposer une méthodologie pour intégrer toutes les corrections, inhérentes à la méthode, à appliquer aux valeurs brutes de réactivité. Une fois la méthode mise au point, le deuxième objectif de ces travaux était la caractérisation de la réactivité atmosphérique totale avec les radicaux OH à Paris, une des rares mégacités existantes en Europe et où aucune mesure de réactivité n'avait été rapportée auparavant. L'étude réalisée pendant la campagne d'hiver 2010 du projet européen MEGAPOLI a permis de caractériser le niveau de réactivité à Paris pendant deux régimes de masses d'air différentes, océanique / continental. Ainsi il a été possible de distinguer un niveau de réactivité purement local de Paris et Ile de France (impacté par le caractère " trafic " de cette ville européenne et étant comparable aux niveaux enregistrés à New York et Tokyo), et un niveau fort, importé, caractéristique d'un transport longue distance. De même, l'étude a révélé que pendant l'import continental, de forts pourcentages ont été enregistrés de réactivité manquante, définie comme la différence entre la valeur mesurée et une valeur théorique, calculée à partir des composés réagissant avec OH et mesurés pendant la campagne. La nature des espèces non-mesurées et contribuant à cette réactivité a été déterminée comme oxydée, issue des processus de " processing " des masses d'air sur le trajet long distance. Ce travail apporte dans un premier temps des informations uniques sur la méthode CRM pour la mesure de la réactivité OH (fonctionnement, traitement des données) et contribue par la suite à la caractérisation des niveaux de réactivité dans la région parisienne.

<p>Radiotherapy is one of the most common therapeutic methods for treatment of many types of cancer. Despite many decades of development and experience there is much to improve, both in efficacy of treatment and to decrease the incidences of adverse healthy tissue reactions. Around 20 % of the radiotherapy patients show a broad range in the severity of normal tissue reactions to radiotherapy, and dose limits are governed by severe reactions in the most radiosensitive patients (< 5 %). Identification of patients with low, moderate or high clinical radiosensitivity before commencing of radiotherapy would allow individual adaptation of the maximum dose with an overall increase in the cure rate. Characterization of factors that may modify the biological effects of ionizing radiation has been a subject of intense research efforts. Still, there is no assay currently available that can reliably predict the clinical radiosensitivity. The aim of this work has been to investigate the role of oxidative stress in individual radiosensitivity and evaluate novel markers of radiation response, which could be adapted for clinical use.</p><p>8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), a general marker of oxidative stress, is one of the major products of interaction of ionizing radiation with DNA and the nucleotide pool of the cell. As 8-oxo-dG is highly mutagenic due to incorrect base pairing with deoxyadenosine, various repair mechanisms recognize and remove 8-oxo-dG. The repaired lesions are released from cells to the extracellular milieu (serum, urine and cell culture medium) where they can be detected as markers for free radical reactions with the nucleic acids.</p><p>Significant variations in background levels as well as in radiation induced levels of 8-oxo-dG in urine have been demonstrated in breast cancer patients (paper 1). Two major patterns were observed: high background and no therapy-related increase vs. low background and significant increase during radiotherapy for the radiosensitive and non radiosensitive patients respectively.</p><p>Studies in paper 2 indicated major contribution of the nucleotide pool to the extracellular 8-oxo-dG levels. The results also implicated induction of prolonged endogenous oxidative stress in the irradiated cells. RNA “knock-down” experiments on the nucleotide pool sanitization enzyme hMTH1 in paper 3 lend further experimental evidence to this assumption.</p><p>The applicability of 8-oxo-dG as a diagnostic marker of oxidative stress was demonstrated in paper 4. Studies on dialysis patients revealed a good correlation between inflammatory responses (known to be associated with persistent oxidative stress) and extracellular 8-oxo-dG.</p><p>In summary, our results confirm that extracellular 8-oxo-dG is a sensitive <i>in vivo</i> biomarker of oxidative stress, primarily formed by oxidative damage of dGTP in the nucleotide pool with a potential to become a clinical tool for prediction of individual responses to radiotherapy.</p>