La lutte contre les « mutilations génitales féminines » (MGF), érigée en cause globale, témoigne de l'insertion paradoxale des sociétés Africaines sur la scène internationale. Pour autant, les politiques anti-MGF qui émergent dans les sociétés excisantes à partir des années 1990 ne sont-elles qu'une réponse automatique aux prescriptions internationales en faveur de l'éradication de ces pratiques ? Adoptant une perspective de sociologie de l'action publique extravertie, le présent travail de thèse explore comment une pratique sociale et culturelle (les MGF) devient un problème et une cause mobilisatrice ; et comment cette cause est politisée, autrement dit traduite dans les champs politiques maliens et kényans. La comparaison du passage de la « mise en sens » à la « mise en action » du problème des MGF, dans un contexte globalisé, met en évidence des trajectoires d'appropriation politique contrastées de la cause. L'appropriation est différentielle dans le cas malien ? avec un cadre d'action publique « maternaliste -éducatif» dominant, faisant de la loi une option « non malienne »; et plutôt mimétique dans le cas kényan ? avec des cadres d'action publique pluralistes moulés sur les mises en sens globales (comme par exemple le Children's Act voté en 2001). Ces différences questionnent les rapports y compris stratégiques à l'extraversion dans le gouvernement des sociétés africaines. Au-delà de la problématique des MGF, cette étude permet donc d'appréhender l' Etat au quotidien, c'est-à-dire en action. Concurrencé, privatisé et réduit à ses fonctions technicistes, il n'en reste pas moins ici la glue d'une gouvernementalité multi-niveaux négociée de la cause des MGF.

L'ADN étant le support de l'information génétique, les lésions de l'ADN provoquées par différents stress physiques ou chimiques sont un défi pour les systèmes de réparation cellulaire. Parmi ceux-ci le système de réparation par excision de bases (BER) implique plusieurs enzymes dont les objectifs sont la reconnaissance et le retrait de la base lésée, fonctions bien connues pour deux glycosylases : Fpg Procaryote et OGG1 Eucaryote. De nombreuses approches ont été décrites pour étudier les interactions ADN/protéine in vitro. Avec la résonance plasmonique de surface par imagerie (SPRi), nous disposons d'une technique d'analyse en temps réel, sans marquage avec laquelle nous avons pu observer des interactions parallélisées d'une même protéine enzymatique purifiée (Fpg, OGG1, EndoIV ou Ape1) vis-à-vis de différentes lésions sur des oligonucléotides de synthèse immobilisés sur une surface d'or. Les dommages étudiés sont une base oxydée (8-oxoG), une base cyclisée (cycloadénine) et des analogues de sites abasiques (THF et C3). Nous avons également étudié l'action de ces mêmes enzymes sur des lésions multiples, en tandem, associant les bases 8-oxoG et 8-oxoA sur le même brin d'ADN. L'originalité de notre dispositif associe l'analyse directe de l'interaction ADN/protéine et l'approche indirecte de sa conséquence par une stratégie d'hybridation et d'amplification du signal après une rampe thermique. Les résultats obtenus permettent d'envisager l'utilisation de notre technique pour observer la réparation simultanée de certaines lésions par des extraits cellulaires pour des travaux de biochimie ou des extraits tissulaires humains pour des travaux de biologie médicale.

Les oxydations sur les bases nucléiques constituent l'une des sources principale d'apparition de lésions sur l'ADN, qui peuvent être mutagènes ou létales pour les cellules en l'absence de réparation de l'ADN. La Formamidopyrimidine-ADN glycosylase (Fpg), une enzyme procaryote du système de réparation de l'ADN par excision de base (BER), initie la réparation d'un large panel de lésions de ce type via ses activités ADN glycosylase (excision de la base oxydée) et AP lyase (clivage du site abasique par β,δ-élimination). Nous avons réalisé des études fonctionnelles par des techniques biochimiques et structurales par cristallographie des rayons X afin de préciser la spécificité de substrat et le mécanisme catalytique de Fpg. Ainsi, nous avons pu mettre en évidence des déterminants structuraux permettant à cette enzyme d'accommoder des lésions de tailles très différentes dans son site actif, en l'occurrence des résidus 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) substitués ou non en N7 par des adduits encombrants. D'autre part, nous avons caractérisé structuralement et fonctionnellement la reconnaissance et l'excision par Fpg d'une lésion pyrimidique, la 5-hydroxy-5-méthyle-hydantoïne (Hyd). Ainsi, nous avons montré que cette lésion appariée à une cytosine était un bon substrat pour l'enzyme, et nous avons précisé structuralement le mode de reconnaissance de l'Hyd par Fpg. D'autre part, nous avons mis en évidence un comportement inattendu de l'enzyme sur ce substrat. En l'occurrence, nous avons montré biochimiquement et structuralement qu'un pontage covalent se formait en quantités non négligeables entre Fpg et l'Hyd dans des conditions physiologiques. Mots clés : Réparation de l'ADN; Réparation par excision de base; Formamidopyrimidine-ADN glycosylase; 2,6- diamino-4-hydroxy-5-formamidopyrimidine; 7,8-dihydro-8-oxo-guanine; 5-hydroxy-5-méthyle-hydantoïne.

<p>Kvinnlig könsstympning uppmärksammades i västvärlden på 1970-talet då invandringen till väst från länder där könsstympning praktiseras ökade. När Waris Dirie gav ut sin självbiografiska bok En blomma i Afrikas öken 1999 kom könsstympning åter på tapeten. Eftersom könsstympning är en sedvänja som praktiserats i tusentals år världen över och fortfarande utövas i flera länder idag, väcktes ett intresse att ta reda på omständigheterna kring fenomenet. Vart, hur och varför uppstod denna till synes inhumana och irrationella sedvänja och hur kommer det sig att den lever kvar än idag? Vilka bakomliggande faktorer finns? Hur hänger könsstympning ihop med religion, kultur, genus, makt och så vidare?</p><p>Eftersom det verkade handla om ett mycket komplext fenomen togs beslutet att syftet skulle vara ganska brett och omfattande. Hypotesen var att könsstympning kunde förklaras och förstås som ett socialt fenomen och detta är det som undersöks, analyseras och framhålls genom denna uppsats. De sociologiska teorier som använts faller inom ramarna för socialpsykologi och som komplement till dessa teorier har även interkulturella perspektiv och genus- och etnicitetsperspektiv använts.</p><p>Metoden är kvalitativ datainsamling. Ett stort urval böcker, artiklar och internetkällor har använts. Dataanalysen har skett parallellt och integrerat med datainsamlingen. Centrala begrepp och teoretiska utgångspunkter har sedan kopplats samman med fenomenet könsstympning i analysen. Slutligen hålls en avslutande diskussion där personliga reflektioner och slutsatser diskuteras.</p><p>Resultatet visar på många olika möjliga sociologiska, interkulturella och genus- och etnicitetsrelaterade förklaringsmodeller av hur könsstympning kan förklaras och förstås som ett socialt fenomen. Det har även visat sig vara intressant att dra paralleller mellan den könsstympade kvinnan och den ”jämställda” västerländska kvinnan. Det finns ingen enkel förklaring till varför sedvänjan existerar än idag, det är många olika aspekter och faktorer som spelar in. Vad som är viktigt är att man förhåller sig till fenomenet med viss kulturell relativism och att man beaktar sedvänjans komplexa och multidimensionella natur.</p> / <p>Female genital mutilation (FGM) attracted much attention in the west in the 1970’s, when the immigration to the west from countries where FGM was practiced increased. When Waris Dirie published her autobiography Desert flower: the extraordinary journey of a desert nomad in 1999, the phenomenon got on the carpet again. Since FGM is a custom that has been practiced for thousands of years all over the world and is still beeing practiced in a number of countries today, an interest was awakened for examining the circumstances surrounding the phenomenon. Where, how and why did this apparently inhumane and irrational custom arise and how come it still exists today? What is at the bottom of it? How is FGM related to religion, culture, gender, power and so on?</p><p>Since it seemed to be about a very complex phenomenon a decision was made to keep the purpose of the essay quite broad and extensive. The hypothesis was that FGM could be explained and understood as a sociological phenomenon and this is what has been examined, analyzed and emphasizwd through out this essay. The sociological theories falls within the framework of social phsychology, and as a compliment to these theories there has also been a use of intercultural perspectives and gender- and ethnicity perspectives.</p><p>The method is qualitative data gathering. A large selection of books, articles and websites have been used. Data analysis has been done throughout and integrated with the data gathering process. In the analysis, theory is related and connected to the pheonomenon FMG. Finally there is a closing discussion in which personal reflections and conclusions are discussed.</p><p>The result shows many different sociological, intercultural and gender- and ethnicity related explanation models of how FGM can be explained and understood as a sociological phenomenon. It has also proved interesting to draw paralleles between the circumcised woman and the “equal” western woman. There is no simple explanation to why the custom is still beeing practiced today, there are many different aspects and factors involved. What is important though, is that you relate to the phenomenon with a certain degree of cultural relativism and that you pay regard to the customs complex and multi dimensional nature.</p>

The understanding of the mesorectal spread in rectal cancer has lead to wide acceptance of total mesorectal excision (TME) as the surgical technique of choice for carcinoma in the lower and mid rectum. While oncological results and survival have improved with TME-surgery, morbidity and mortality remain important issues. The most feared complication is symptomatic anastomotic leakage. The aim of this thesis was to focus on the role of the defunctioning stoma, risk factors, and postoperative monitoring in regard to anastomotic leakage in sphincter saving resection of the rectum. Intraoperative adverse events were analysed in a retrospective population based case-control study in which all patients who underwent elective anterior resection in Sweden between 1987 and 1995, and who died within 30 days or during the initial hospital stay (n=140), were compared with patients chosen at random (n=423) who underwent the same operation during the same period, but survived the operation. Intraoperative adverse events were more frequent in those who died, and reconstruction of an anastomosis judged unsatisfactory by the surgeon improved the outcome. In a population based retrospective case-control study, risk factors for symptomatic anastomotic leakage were investigated in randomly chosen sample of patients who underwent anterior resection in Sweden between 1987 and 1995 (n=432). Twelve per cent of the patients developed symptomatic leakage, and 25% of the patients with leakage ended up with a permanent stoma. In multivariate regression analysis, low anastomosis, preoperative radiotherapy, male gender and intraoperative adverse events were independent riskfactors for anastomotic leakage. In a randomised multicentre trial patients operated with sphincter saving TME¨surgery for rectal cancer were randomised to a defunctioning stoma (n=116) or not (n=118). The overall rate symptomatic leakage was 19%. Patienst without a defunctioning stoma leaked in 28% and patients with a defunctioing stoma in 10%, a statistically significant difference (p&lt;0.001) not previously demonstrated in any randomised trial of adequate size. Postoperative monitoring with computed tomography scan (CT-scan) on postoperative day 2 and 7, and C-reactive protein (CRP) daily in 33 patients operated on with anterior resection of the rectum, demonstrated larger pelvic fluid collections in patients with leakage before the leakage was clinically diagnosed. CRP was increased from postoperative day 2 and onwards in patients in whom clinical leakage was diagnosed on median postoperative day 8. In 23 patients who underwent anterior resection of the rectum, intraperitoneal metabolism was investigated using microdialysis technique measuring the carbohydrate metabolites lactate, pyruvate and glucose. Intraperitoneal cytokines IL-6, IL-10 and TNF-α were collected through a pelvic drain and analysed. In patients who developed leakage, the latate/pyruvate ratio was increased near the anastomosis on postoperative day 5 and 6, as well as IL-6 and IL-10 which were increased postoperatively day 1 and 2, while TNF-α was higher on day 1.

Kvinnlig könsstympning uppmärksammades i västvärlden på 1970-talet då invandringen till väst från länder där könsstympning praktiseras ökade. När Waris Dirie gav ut sin självbiografiska bok En blomma i Afrikas öken 1999 kom könsstympning åter på tapeten. Eftersom könsstympning är en sedvänja som praktiserats i tusentals år världen över och fortfarande utövas i flera länder idag, väcktes ett intresse att ta reda på omständigheterna kring fenomenet. Vart, hur och varför uppstod denna till synes inhumana och irrationella sedvänja och hur kommer det sig att den lever kvar än idag? Vilka bakomliggande faktorer finns? Hur hänger könsstympning ihop med religion, kultur, genus, makt och så vidare? Eftersom det verkade handla om ett mycket komplext fenomen togs beslutet att syftet skulle vara ganska brett och omfattande. Hypotesen var att könsstympning kunde förklaras och förstås som ett socialt fenomen och detta är det som undersöks, analyseras och framhålls genom denna uppsats. De sociologiska teorier som använts faller inom ramarna för socialpsykologi och som komplement till dessa teorier har även interkulturella perspektiv och genus- och etnicitetsperspektiv använts. Metoden är kvalitativ datainsamling. Ett stort urval böcker, artiklar och internetkällor har använts. Dataanalysen har skett parallellt och integrerat med datainsamlingen. Centrala begrepp och teoretiska utgångspunkter har sedan kopplats samman med fenomenet könsstympning i analysen. Slutligen hålls en avslutande diskussion där personliga reflektioner och slutsatser diskuteras. Resultatet visar på många olika möjliga sociologiska, interkulturella och genus- och etnicitetsrelaterade förklaringsmodeller av hur könsstympning kan förklaras och förstås som ett socialt fenomen. Det har även visat sig vara intressant att dra paralleller mellan den könsstympade kvinnan och den ”jämställda” västerländska kvinnan. Det finns ingen enkel förklaring till varför sedvänjan existerar än idag, det är många olika aspekter och faktorer som spelar in. Vad som är viktigt är att man förhåller sig till fenomenet med viss kulturell relativism och att man beaktar sedvänjans komplexa och multidimensionella natur. / Female genital mutilation (FGM) attracted much attention in the west in the 1970’s, when the immigration to the west from countries where FGM was practiced increased. When Waris Dirie published her autobiography Desert flower: the extraordinary journey of a desert nomad in 1999, the phenomenon got on the carpet again. Since FGM is a custom that has been practiced for thousands of years all over the world and is still beeing practiced in a number of countries today, an interest was awakened for examining the circumstances surrounding the phenomenon. Where, how and why did this apparently inhumane and irrational custom arise and how come it still exists today? What is at the bottom of it? How is FGM related to religion, culture, gender, power and so on? Since it seemed to be about a very complex phenomenon a decision was made to keep the purpose of the essay quite broad and extensive. The hypothesis was that FGM could be explained and understood as a sociological phenomenon and this is what has been examined, analyzed and emphasizwd through out this essay. The sociological theories falls within the framework of social phsychology, and as a compliment to these theories there has also been a use of intercultural perspectives and gender- and ethnicity perspectives. The method is qualitative data gathering. A large selection of books, articles and websites have been used. Data analysis has been done throughout and integrated with the data gathering process. In the analysis, theory is related and connected to the pheonomenon FMG. Finally there is a closing discussion in which personal reflections and conclusions are discussed. The result shows many different sociological, intercultural and gender- and ethnicity related explanation models of how FGM can be explained and understood as a sociological phenomenon. It has also proved interesting to draw paralleles between the circumcised woman and the “equal” western woman. There is no simple explanation to why the custom is still beeing practiced today, there are many different aspects and factors involved. What is important though, is that you relate to the phenomenon with a certain degree of cultural relativism and that you pay regard to the customs complex and multi dimensional nature.

No description available.

FACT est une protéine clé, qui joue de multiples rôles, y compris dans la transcription et la réparation de l'ADN endommagé. Néanmoins, comment FACT participe à la réparation et à la transcription de la chromatine n'est pas élucidé. Dans ce travail nous avons tout d'abord étudié le rôle de FACT dans le processus de réparation par excision de base (BER). Nous avons utilisé des nucléosomes reconstitués avec de l'ADN à uracile incorporé au hasard. Nous avons trouvé que l'enzyme UDG est capable d'enlever les uraciles localisés du côté de la solution et pas les uraciles se trouvant en face de l'octamère d'histone. La présence simultanée de FACT et de RSC (facteur de remodelage de la chromatine, impliqué dans la réparation) permet un enlèvement efficace des uraciles localisés du côté de l'octamère d'histone par l'UDG. De plus, l'action concertée de FACT et RSC contribue à l'enlèvement de la lésion oxidative 8-oxoG, autrement inaccessible, de la matrice nucléosomale par l'enzyme OGG1. Ce résultat est obtenu grâce à une activité " co-remodelatrice " de la protéine FACT. Dans ce travail nous décrivons pour la première fois cette nouvelle propriété de FACT et nous montrons par une série d'expériences biochimiques que FACT est capable de stimuler l'activité de remodelage du RSC. Nos expériences montrent que la présence de FACT augmente l'efficacité de RSC à transformer l'énergie libérée par l'hydrolyse de l'ATP en travail " mécanique ". Les données obtenues suggèrent une nature stochastique du BER in vivo, FACT étant un facteur clé dans le processus de réparation. Nous avons également investigué l'implication de l'activité co-remodelatrice de FACT dans la fixation de NF-kB aux matrices nucléosomales. La production de nucléosomes remodelés, mais non - mobilisés (remosomes) n'est pas suffisante pour promouvoir la fixation de NF-kB. Pourtant, la mobilisation des nucléosomes par l'intermédiaire de RSC permet une interaction efficace entre NF-kB et l'ADN nucléosomal. Toutes ces données sont essentielles pour le décryptage du mécanisme moléculaire par lequel FACT agit dans le BER et dans la transcription médiée par NF-kB.

Made available in DSpace on 2014-12-17T14:05:23Z (GMT). No. of bitstreams: 1 ThayseAS_TESE.pdf: 2133799 bytes, checksum: c236c1e72798e2c7e1008d1c78d046a4 (MD5) Previous issue date: 2013-03-21 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / In vitro and in animal models, APE1, OGG1, and PARP-1 have been proposed as being involved with inflammatory response. In this work, we have investigated if the SNPs APE1 Asn148Glu, OGG1 Ser326Cys, and PARP-1 Val762Ala are associated to meningitis and also developed a system to enable the functional analysis of polymorphic proteins. Patients with bacterial meningitis (BM), aseptic meningitis (AM) and controls (non-infected) genotypes were investigated by PIRA-PCR or PCR-RFLP. DNA damages were detected in genomic DNA by Fpg treatment. IgG and IgA were measured from plasma and the cytokines and chemokines were measured from cerebrospinal fluid samples using Bio-Plex assays. The levels of NF-?B and c-Jun were measured in CSF by dot blot assays. A significant (P<0.05) increase in the frequency of APE1 148Glu allele in BM and AM patients was observed. A significant increase in the genotypes Asn/Asn in control group and Asn/Glu in BM group was also found. For the SNP OGG1 Ser326Cys, the genotype Cys/Cys was more frequent (P<0.05) in BM group. The frequency of PARP-1 Val/Val genotype was higher in control group (P<0.05). The occurrence of combined SNPs increased significantly in BM patients, indicating that these SNPs may be associated to the disease. Increasing in sensitive sites to Fpg was observed in carriers of APE1 148Glu allele or OGG1 326Cys allele, suggesting that SNPs affect DNA repair activity. Alterations in IgG production were observed in the presence of SNPs APE1Asn148Glu, OGG1Ser326Cys or PARP-1Val762Ala. Reductions in the levels ofIL-6, IL-1Ra, MCP-1/CCL2and IL-8/CXCL8 were observed in the presence of APE1148Glu allele in BM patients, however no differences were observed in the levels of NF-?B and c-Jun considering genotypes and analyzed groups. Using APE1 as model, a system to enable the analysis of cellular effects and functional characterization of polymorphic proteins was developed using strategies of cloning APE1 cDNA in pIRES2-EGFP vector, cellular transfection of the construction obtained, siRNA for endogenous APE1 and cellular cultures genotyping. In conclusion, we obtained evidences of an effect of SNPs in DNA repair genes on the regulation of immune response. This is a pioneering work in the field that shows association of BER variant enzymes with an infectious disease in human patients, suggesting that the SNPs analyzed may affect immune response and damage by oxidative stress level during brain infection. Considering these data, new approaches of functional characterization must be developed to better analysis and interactions of polymorphic proteins in response to this context / Estudos in vitro e em modelos animais sugerem que as prote?nas de reparo de DNA da via de reparo por excis?o de bases (do ingl?s, BER) APE1, OGG1 e PARP-1 est?o envolvidas tamb?m na resposta inflamat?ria. Neste trabalho foi investigado se os SNPs APE1 Asn148Glu, OGG1 Ser326Cys e PARP-1 Val762Ala associam-se ? meningite, e foi desenvolvido um sistema para an?lise funcional destas variantes polim?rficas. Os gen?tipos de pacientes com meningite bacteriana (MB), meningite ass?ptica (MA) e n?o infectados (controles) foram investigados por PIRA-PCR ou PCR-RFLP. Danos no DNA gen?mico foram detectados por meio de tratamento com Fpg. IgG e IgA foram titulados no plasma e citocinas e quimiocinas foram mensuradas em amostras de l?quor atrav?s de ensaios em Bio-Plex. Os n?veis de NF-?B e c-Jun foram dosados no l?quor dos pacientes por meio de dot blot. Foi observado um aumento significativo (P<0.05) na frequ?ncia do alelo APE1 148Glu nos casos de MB e MA. Os gen?tipos Asn/Asn no grupo controle e Asn/Glu no grupo da MB tamb?m apresentaram relevante aumento em suas frequ?ncias (P<0.05). Para o SNP OGG1 Ser326Cys, o gen?tipo Cys/Cys esteve mais frequente (P<0.05) nos casos de MB. A frequ?ncia do gen?tipo PARP-1 Val/Val foi mais alta no grupo controle (P<0.05). A ocorr?ncia combinada dos SNPs foi significativamente alta nos pacientes com MB, indicando que estes SNPs podem estar associados ? doen?a. Os portadores do alelo APE1 148Glu ou OGG1 326Cys apresentaram um n?mero maior de s?tios sens?veis ? Fpg, sugerindo que os SNPs afetam a atividade de reparo do DNA. Altera??es na s?ntese de IgG foram observadas na presen?a dos SNPs APE1 Asn148Glu, OGG1 Ser326Cys ou PARP-1 Val762Ala. Redu??es nos n?veis de IL-6, IL-1Ra, MCP-1/CCL2 e IL-8/CXCL8 foram encontradas na presen?a do alelo APE1 148Glu em amostras de pacientes com MB, no entanto n?o foram encontradas diferen?as nos n?veis de NF-?B e c-Jun considerando os gen?tipos e os grupos analisados. Utilizando APE1 como modelo, foi desenvolvido um sistema que possibilita a express?o e caracteriza??o funcional das enzimas polim?rficas estudadas e seus efeitos na c?lula, por meio de clonagem, utilizando o vetor pIRES2-EGFP e cDNA de APE1, transfec??o celular da constru??o obtida, inibi??o por siRNA de APE1 end?gena e genotipagem de culturas celulares. Em conclus?o, foram obtidas evid?ncias de um efeito significativo dos SNPs nos genes de reparo de DNA na regula??o da resposta imunol?gica. Este ? um trabalho pioneiro na ?rea, que demonstra a associa??o de variantes das enzimas da via BER com uma doen?a infecciosa em humanos, sugerindo que os SNPs estudados podem afetar a resposta imune e o impacto do n?vel de estresse oxidativo durante a infec??o cerebral. Desta forma, novos meios de an?lise funcional devem ser desenvolvidos para estudo de prote?nas polim?rficas e suas intera??es neste contexto / 2020-01-01

O câncer é a primeira causa de mortes por doença, após 1 ano de idade, até o final da adolescência, excetuando aquelas relacionadas aos acidentes e à violência. A Leucemia Linfoide Aguda (LLA) afeta células linfoides e agrava-se rapidamente. São os tumores mais frequentes na infância e representam um terço de todas as neoplasias malignas nesta faixa etária. Em média, a taxa de cura excede 70%, todavia, apesar dos avanços das últimas décadas, os índices de crianças que apresentam recidiva da doença continua significativo. Danos endógenos ao DNA ocorrem numa frequência altíssima, além dos danos causados por terapias antitumorais. Alteração no reparo ao dano do DNA pode induzir mecanismos de resistência ao tratamento quimioterápico, resultando em aumento do reparo de lesões do DNA. Reparo por Excisão de Nucleotídeos (NER) é a via de reparo de DNA mais versátil e flexível nas células. Seus componentes estão sendo estudados como biomarcadores de prognóstico e terapias-alvo. No entanto, alguns relatórios têm abordado danos de DNA em Leucemia Linfoide Aguda (LLA) pediátrica. Neste estudo, realizamos um estudo de acompanhamento observacional em pacientes pediátricos para avaliar os danos do DNA pelo Ensaio Cometa Alcalino e expressão gênica da via de NER durante a indução da quimioterapia. Amostras de medula óssea (MO) ao diagnóstico, dia 15 (D15) e 30 (D30) do tratamento foram coletadas de 28 pacientes com LLA. Não houve aumento no índice de dano. No entanto, houve uma redução de células com baixo danos na comparação do D35 com o diagnóstico. Este resultado se confirmou em pacientes que apresentaram doença residual mínima positiva. A via de NER permaneceu constante, no entanto, em um único paciente, foi observada uma diminuição significativa da expressão dos genes, talvez devido ao silenciamento ou a regulação negativa das vias de reparo. Níveis de danos e reparação do DNA podem influenciar o resultado clínico, estar envolvidos na resistência aos fármacos e potencializar o risco de recidiva. Este é o primeiro estudo que avalia o dano ao DNA em amostras de MO de pacientes pediátricos com LLA. Apesar do pequeno número de pacientes alocados para o estudo, a partir dos achados é possível concluir que complexos de reparo merecem ser investigados a curto e a longo prazo. Acompanhamento dos resultados do paciente vai ajudar a elucidar a implicação dos nossos achados em taxas de cura e de recidiva. / Cancer is the leading cause of death by disease after 1 year old until the end of adolescence, except those related to accidents and violence. Acute Lymphoid Leukemia (ALL) affects lymphoid cells and worsens quickly. They are the most frequent tumors in childhood and account for a third of all malignancies in this age group. On average, the cure rate exceeds 70%, however, despite the progress of recent decades, rates of children with disease recurrence remains significant. Endogenous DNA damage occurs at a very high frequency, in addition to the damage caused by anti-tumor therapies. Change in the repair of DNA damage can induce resistance mechanisms to chemotherapy, resulting in increased repair of DNA lesions. Nucleotide Excision Repair (NER) pathway is the more versatile and flexible DNA repair in cells. Its components are being studied as prognostic biomarkers and targeted therapies. However, there are some reports of DNA damage in pediatric Acute Lymphoid Leukemia (ALL). In this study, we conducted an observational follow-up study in pediatric patients to assess DNA damage by alkaline comet assay and gene expression of NER pathway during induction chemotherapy. Bone marrow (BM) samples at diagnosis, 15th (D15) and 30th (D30) of treatment were collected from 28 patients with ALL. There was no increase in damage index. However, there was a reduction of cells with low damage in comparison to the D35 diagnosis. This result was confirmed in patients with positive minimal residual disease. The NER pathway remained constant, however, in one patient, a significant decrease of gene expression was observed perhaps due to the silencing or down-regulation of repair pathways. Damage levels and DNA repair can influence the clinical result and may be involved in drug resistance and enhance the risk of recurrence. This is the first study to assess DNA damage in BM samples of pediatric patients with ALL. Despite the small number of patients allocated to the study, from the findings we conclude that repair complex deserves to be investigated in the short and long term. Monitoring patient’s outcomes will help to access the implication of our findings in cure and relapse rates.