No description available.

Dans les pays en voie de développement, les évolutions prévues par les organismes internationaux montrent une progression beaucoup plus importante des maladies chroniques non transmissibles, comme le cancer, que des maladies transmissibles. Actuellement, la majorité des études montre que la tendance à l'augmentation de l'incidence et de la mortalité par cancer colorectal est plus marquée dans les sociétés riches que dans les sociétés pauvres. Dans les pays développés le cancer colorectal est au deuxième rang en ce qui concerne la mortalité par cancer et les changements dans les habitudes alimentaires et le mode de vie sont souvent mis en cause dans son développement. Bien que les données épidémiologiques soient rares, les populations de la plupart des pays asiatiques ne sont pas conscientes du risque grandissant que peut constituer pour eux le cancer colorectal. Comme les autres pays en développement, le Cambodge n'a pas de système d'enquête de consommation alimentaire, ni de système de surveillance ou de contrôle des substances chimiques, ni de système d'enregistrement, de contrôle ou de dépistage des cancers. L'objectif de cette recherche était de débuter la première observation d'une relation entre régime alimentaire et cancer colorectal au Cambodge. L'idée générale était d'identifier les aliments grands contributeurs des régimes alimentaires de la population cambodgienne, et de les traduire en calories, nutriments et composés bioactifs en se fondant sur les bases de données existantes. Une étude a également été menée sur les comportements de cette population, en ce qui concerne ses habitudes alimentaires et les modes de préparation des aliments susceptibles de produire des substances cancérigènes telles que des amines hétérocycliques (AH) et du benzo[a]pyrene (BaP). Pour réaliser ce travail de recherche, une enquête de consommation alimentaire a été effectuée à l'aide d'un rappel sur 24 heures et d'un questionnaire de fréquence alimentaire, afin de créer une base de données dédiée pour servir à l'évaluation des risques. Ensuite, une évaluation de l'exposition aux AH et BaP a été effectuée, afin d'établir une hiérarchie du risque que ces substances posent pour cette population d'étude ; celle-ci a été réalisée en croisant les données de consommation alimentaire, obtenues par le biais d'une enquête de consommation alimentaire individuelle exécutée dans ce travail, avec les données de contamination rassemblées à partir des analyses chimiques reportées dans la littérature scientifique récente. Les résultats ont été comparés avec les valeurs toxicologiques de référence. Ils ont montré que les habitudes alimentaires au Cambodge n'ont pas encore changé pour s'adapter à l'alimentation occidentale, et qu'elles offrent plus de composés protecteurs. L'exposition aux contaminants néoformés (AH et BaP) a été plus faible par rapport aux pays régionaux ainsi qu'aux pays développés. La présence de composés endogènes tels que glucides, fibres alimentaires, calcium et vitamine C semble protéger la population cambodgienne du cancer colorectal. Des recherches supplémentaires sont nécessaires pour étudier les interactions entre l'alimentation, le mode de vie et les facteurs génétiques, ainsi que d'autres facteurs également. / From the projection in the future of international bodies, non-communicable diseases such as cancer may increase more than communicable diseases in developing countries. The highlight of this burden may be due to the changing of dietary patterns and lifestyle. Currently, the evolution of food consumption, consumption pattern and colorectal cancer is very worrying worldwide. It is a disease in economically ‘developed' populations, and it is the second killer among other cancers; however, its incidence seems lower in poor countries. As the other developing countries, Cambodia has no system of food survey, no monitoring and control system of chemical substances, and also, there is no control and registration system for cancer. Thus, the objective of this research was to start the first observation of the relationship between dietary pattern and colorectal cancer in Cambodia. The general idea of the study was to identify the dietary patterns, and larger contributors to colorectal cancer in Cambodia, then to translate them into calories, nutrients and bioactive compounds, based on the existing database. Another goal was to assess the difference of dietary habit and cooking methods in the studied population that could lead to the production of colorectal carcinogens such as heterocyclic amines (HAs) and benzo[a]pyrene (BaP). In order to create the food consumption database needed for food risk assessment, a food consumption survey was conducted using 24-hour recall and food frequency questionnaire. A dietary assessment of HAs and BaP has been done, in order to establish a hierarchy of the importance of the risk that these substances represent to the health of this population. Dietary exposures to HAs and BaP were obtained by combining food consumption data, obtained from the individual food survey specially designed and carried out during this research, with the contamination data gathered from chemical analysis reported in the recent literature. The observation results have been compared with the toxicological reference values. The results show that dietary patterns in Cambodia have not changed yet to adapt to the Western diet, and contain higher levels of protected nutrients. The exposure to neoformed contaminants (HAs and BaP) was lower than the values reported among other Asian countries, and lowest as compared to the developed countries. The presence of endogenous compounds such as carbohydrates, dietary fibers, calcium and vitamin C, seems to protect the Cambodian population from colorectal cancer. Further research is needed to study the interaction of diet, lifestyle and the genetic background, and other factors as well.

A inflamação é um componente essencial presente no microambiente tumoral, sendo relacionada a muitos tipos de câncer, como o de pulmão e de fígado. O objetivo foi estudar a influência de fatores genéticos relacionados à inflamação no desenvolvimento do câncer através da análise da progressão tumoral em camundongos AIRmax e AIRmin, geneticamente selecionados para máxima ou mínima resposta inflamatória. Os carcinomas foram induzidos pela injeção de Uretana ou DEN. 32 semanas após dose, a maioria dos AIRmax apresentaram tumores hepáticos, enquanto AIRmin foram resistentes. O contrário aconteceu com câncer de pulmão: todos os AIRmin foram acometidos e poucos AIRmax apresentaram pequenas lesões. As proteínas de fase aguda IL-6, TNF<font face=\"Symbol\">a e IL-1<font face=\"Symbol\">b são importantes nesse processo, pois tiveram aumento de produção em órgãos alvo horas após injeção. Esses resultados sugerem que um grupo de loci gênicos controla a resposta inflamatória e a susceptibilidade/resistência a diversos tipos de câncer e ressaltam o papel específico de células locais no controle da imunidade ao tumor. / Inflammatory components are an essential part of the tumor microenvironment being crucial in some types of cancer. Our objective was to study the influence of genetic factors relevant to inflammatory response regulation on cancer development by the comparative analysis of carcinogen-induced liver and lung tumors in AIRmax and AIRmin mouse strains, genetically selected for maximum and minimum inflammatory responsiveness. The carcinomas were induced by the injection of Urethane or DEN. 32 weeks after treatment, most AIRmax had liver tumors whereas AIRmin mice were resistant. The inverse occured in lungs: all AIRmin were affected and the incidence in AIRmax was 27.3%. The acute phase proteins IL-6, TNF<font face=\"Symbol\">a and IL-1<font face=\"Symbol\">b seem to be important in this process, with increased production in target organs hours after drug injection. These results provide a demonstration that a group of genes controls the inflammatory response and susceptibility or resistance to different types of cancers and also highlight the specific role of local cells in the control of tumor immunity.

Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2018-02-08T16:59:29Z No. of bitstreams: 1 nayarafernandespedro_dissert.pdf: 4222502 bytes, checksum: 54d2642c2adb8a61ed1b790de37706e3 (MD5) / Made available in DSpace on 2018-02-08T16:59:29Z (GMT). No. of bitstreams: 1 nayarafernandespedro_dissert.pdf: 4222502 bytes, checksum: 54d2642c2adb8a61ed1b790de37706e3 (MD5) Previous issue date: 2016-10-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Introduction: Susceptibility for head and neck cancer is modulated by environmental and genetics factors. About 90% of these tumors are classified as head and neck squamous cells carcinoma which develops in the mucosal surface of the upper aero digestive tract. Alteration of the biotransformation mechanism of exogenous compounds can result in production of damaging substances and predispose to malignant cell development. Reactive oxygen species (ROS) are the result of biotransformation metabolism performed by antioxidant enzymes. Alteration of the expression or activity of these enzymes can lead to the increase of intra and extracellular ROS, which are able to promote oxidative damage in the cell, DNA mutation and disequilibrium of the cellular homeostasis which converge in pathological conditions such as cancer. Objectives: The present study evaluated the expression of genes involved in Phase II metabolism of exogenous compounds in oral squamous cells carcinoma (OSCC). Casuistic and Methods: Eight samples of OSCC and adjacent non tumor tissues were analyzed. The relative quantification of 84 genes involved in the antioxidant system was performed by quantitative real time Polymerase Chain Reaction in Real Time using the TaqMan Array Human Antioxidant Mechanisms (Applied Biosystems). Statistical analyses were performed using D'Agostino & Pearson omnibus normality test, One-sample T test, Wilcoxon signed rank test, Two-sample T Test and Mann-Whitney test. Results: Twenty-one genes presented differential expression in OSCC (P<0.05). Four genes exhibited high expression (ATOX1, PRDX4, PRNP and SOD2) and seventeen genes presented reduced expression (ALOX12, CAT, CSDE1, DHCR24, DUOX1, DUOX2, EPHX2, GLRX2, GPX3, GSR, GSTZ1, MGST3, PRDX1, OXR1, OXSR1, SOD1 and SOD3). The differential expressed genes are related to biological processes involved in carcinogenesis, such as inflammation, angiogenesis, apoptosis, genomic instability, invasion, survival and cell proliferation. Gene expression was not associated to clinic and pathologic parameters of the tumors. Conclusion: Genes encoding enzymes involved in the antioxidant metabolism of exogenous compounds present differential expression in OSCC. Alteration in the expression of these genes can modulate biological processes related to detoxification of toxic compound and predispose to malignant cell growth in the oral cavity. / Introdução: A suscetibilidade ao câncer de cabeça e pescoço é modulada por fatores ambientais e genéticos. Cerca de 90% destes tumores são classificados como carcinoma espinocelular de cabeça e pescoço, que se desenvolve nas superfícies mucosas do trato aéreo digestivo superior. Alterações no mecanismo de biotransformação de compostos exógenos podem resultar na geração de substâncias nocivas e predispor à malignização celular. Espécies reativas de oxigênio (EROs) resultam do metabolismo biotransformativo realizado por enzimas antioxidantes. Alterações na expressão ou na atividade dessas enzimas podem levar ao aumento de EROs intra e extracelular, que são capazes de promover danos oxidativos à célula, mutações no DNA e desequilíbrio na homeostase celular, que convergem em estados patológicos como o câncer. Objetivo: O presente estudo avaliou a expressão de genes envolvidos no metabolismo antioxidante (Fase II) de compostos exógenos em carcinoma espinocelular de cavidade oral (CEC oral). Casuística e Métodos: Foram analisadas oito amostras de CEC oral e oito tecidos não tumorais adjacentes. A quantificação da expressão de 84 genes envolvidos no sistema de antioxidação foi realizada por Reação em Cadeia da Polimerase quantitativa em tempo real utilizando o kit TaqMan Array Human Antioxidant Mechanisms (Applied Biosystems). As análises estatísticas foram realizadas por D'Agostino & Pearson omnibus normality test, Onesample T test, Wilcoxon signed rank test, Two-sample T Test e Mann-Whitney test. Resultados: Vinte e um genes apresentaram expressão diferencial em CEC oral (P<0,05). Quatro genes exibiram expressão elevada (ATOX1, PRDX4, PRNP e SOD2) e dezessete expressão reduzida (ALOX12, CAT, CSDE1, DHCR24, DUOX1, DUOX2, EPHX2, GLRX2, GPX3, GSR, GSTZ1, MGST3, PRDX1, OXR1, OXSR1, SOD1 e SOD3). Os genes diferencialmente expressos estão relacionados a processos biológicos envolvidos na carcinogênese, tais como inflamação, angiogênese, apoptose, instabilidade genômica, invasão, sobrevivência e proliferação celular, e podem contribuir para o desenvolvimento do carcinoma espinocelular de cavidade oral. A expressão gênica não apresentou associação com os parâmetros clínicos e histopatológicos dos tumores. Conclusão: Genes que codificam enzimas envolvidas no metabolismo de antioxidação de compostos exógenos apresentam expressão diferencial em CEC oral. Alterações na expressão desses genes podem modular processos biológicos relacionados à detoxificação de compostos tóxicos à célula e predispor à malignização celular na cavidade oral.

A inflamação é um componente essencial presente no microambiente tumoral, sendo relacionada a muitos tipos de câncer, como o de pulmão e de fígado. O objetivo foi estudar a influência de fatores genéticos relacionados à inflamação no desenvolvimento do câncer através da análise da progressão tumoral em camundongos AIRmax e AIRmin, geneticamente selecionados para máxima ou mínima resposta inflamatória. Os carcinomas foram induzidos pela injeção de Uretana ou DEN. 32 semanas após dose, a maioria dos AIRmax apresentaram tumores hepáticos, enquanto AIRmin foram resistentes. O contrário aconteceu com câncer de pulmão: todos os AIRmin foram acometidos e poucos AIRmax apresentaram pequenas lesões. As proteínas de fase aguda IL-6, TNF<font face=\"Symbol\">a e IL-1<font face=\"Symbol\">b são importantes nesse processo, pois tiveram aumento de produção em órgãos alvo horas após injeção. Esses resultados sugerem que um grupo de loci gênicos controla a resposta inflamatória e a susceptibilidade/resistência a diversos tipos de câncer e ressaltam o papel específico de células locais no controle da imunidade ao tumor. / Inflammatory components are an essential part of the tumor microenvironment being crucial in some types of cancer. Our objective was to study the influence of genetic factors relevant to inflammatory response regulation on cancer development by the comparative analysis of carcinogen-induced liver and lung tumors in AIRmax and AIRmin mouse strains, genetically selected for maximum and minimum inflammatory responsiveness. The carcinomas were induced by the injection of Urethane or DEN. 32 weeks after treatment, most AIRmax had liver tumors whereas AIRmin mice were resistant. The inverse occured in lungs: all AIRmin were affected and the incidence in AIRmax was 27.3%. The acute phase proteins IL-6, TNF<font face=\"Symbol\">a and IL-1<font face=\"Symbol\">b seem to be important in this process, with increased production in target organs hours after drug injection. These results provide a demonstration that a group of genes controls the inflammatory response and susceptibility or resistance to different types of cancers and also highlight the specific role of local cells in the control of tumor immunity.

This thesis focuses on exacerbating chemicals risk in workplaces under the background of rapid industrialization in developing countries. The overall aim is to investigate the development of regulatory tools which aim at minimizing the health risks from chemical substances in the workplace. The contents of the thesis are divided into three sections: the profile of occupational diseases in China (paper I), occupational exposure limits (paper II and III), and comparison between chemicals regulat ions in Europe and China (paper IV). Paper I presents an analysis of the development of occupational diseases in China between 2000 and 2010. The number of recorded cases of occupational diseases increased rapidly in China during this period and the majority of cases were attributable to dust and other chemicals exposures. Difficulties in diagnosis and inefficient surveillance are major impediments to the proper identification and mitigation of occupational diseases. Migrant workers are extremely vulnerable to occupational hazards. Paper II investigates the state of harmonization of OELs between twenty-five OEL systems in Europe and Asia. The majority of the investigated organizations declare themselves to have been influenced by the American Conference of Governmental Industrial Hygienists (ACGIH), and in many cases this can be empirically confirmed. However, large international differences still exist in substance selection and in the level of OELs among organizations. Paper III explores the setting of risk-based OELs on non-threshold carcinogens. Relatively few agencies set risk-based OELs. Differences exist in policy, both regarding the magnitude of risk considered as tolerable or acceptable and whether a general risk level or case-by-case substance-specific risk levels are determined. In regards to the level of the OELs both differences in science and policy contribute, and it was not possible to determine which has the larger influence. Paper III explores the setting of risk-based OELs on non-threshold carcinogens. Relatively few agencies set risk-based OELs. Differences exist in policy, both regarding the magnitude of risk considered as tolerable or acceptable and whether a general risk level or case-by-case substance-specific risk levels are determined. In regards to the level of the OELs both differences in science and policy contribute, and it was not possible to determine which has the larger influence. Paper IV systematically compares the regulation systems for chemicals in the EU and China in terms of substances covered, requirement on information, risk assessment and risk management. It shows that the European and Chinese chemicals legislations are remarkably similar.The differences are larger in terms of substance coverage and data requirements than in terms of risk assessment and management. Substitution of hazardous substances is driven more by updates of the EU regulatory system than of the Chinese system. / <p>QC 20130830</p>

N-Nitrosamines are an emerging group of disinfection byproducts characterized by high carcinogenic risks at ng/L levels and by their frequent detection in water and wastewater treatment systems in the U.S. and other parts of the world. The overall goal of this research is to achieve a better understanding of the roles of common nitrosamine precursors in leading to N-nitrosamine formation in water and wastewater treatment systems. The specific objectives of this research are: (a) To probe the mechanisms of nitrosamine formation from commonly employed water treatment polymers, particularly polyDADMACs, during ozonation, (b) To evaluate the role of dithiocarbamate compounds as nitrosamine precursors in reaction with common water disinfection oxidants, and (c) To investigate the potential enhancement effect of activated carbons (AC) to promote transformation of amines to nitrosamines and identify the involved reaction mechanism. Results of this research show that, upon ozonation, polyDADMACs may yield N-nitrosodimethylamine (NDMA) at levels up to two orders of magnitude higher than current advisory guidelines for NDMA. Radical pathways may be responsible for the degradation of the quaternary ammonium ring groups in polyDADMACs to release of dimethylamine (DMA). Detection of significant amounts of nitrite after ozonation of polyDADMACs and DMA suggests the potential role of nitrosation pathway in NDMA formation. Study results also reveal dithiocarbamates as potent nitrosamine precursors with significant nitrosamine yields upon ozonation and monochloramination. Identification and quantification of reaction products suggest nitrosation and chlorinated-UDMH oxidation as primary reaction mechanisms in nitrosamine formation from ozonation and monochloramination of dithiocarbamates compounds, respectively. This research also demonstrates that many commercial AC materials may catalyze transformation of secondary amines to yield trace levels of N-nitrosamines under ambient aerobic conditions. This is a novel discovery with far-reaching implications because of the widespread usage of AC materials in numerous analytical and environmental applications. The study results show that the properties of AC materials and reaction conditions play a crucial role in the catalyzed nitrosamine formation and should be carefully selected to minimize analytical errors and undesirable nitrosamine formation in water samples. Overall, the mechanistic information obtained in this research will be useful for the water industry and research communities to develop more effective strategies to control undesirable nitrosamine formation in water and wastewater treatment systems and thus better protect the public health.

Background: Meat consumption is associated with an elevated risk of colorectal cancer (CRC); exposure to heterocyclic aromatic amines (HAAs), carcinogens produced when meat is cooked at high temperatures, is one hypothesized explanation for this relationship. HAAs form adducts with DNA; left unrepaired, DNA adducts can induce mutations which may initiate and/or promote the development of colorectal adenomas, precursors to the vast majority of CRCs. Along this continuum, genetic differences in the ability to biotransform or metabolize HAAs and repair DNA is postulated to modify the HAA-CRC relationship. Methods: This thesis examined the HAA-CRC relationship in two studies (Phase 1 and 2). In a cross-sectional study of 99 healthy volunteers, Phase 1 investigated the relationship between dietary exposure to HAAs and the levels of bulky DNA adducts in blood leukocytes. In Phase 2, a cross-sectional study examined the relationships between dietary exposures to: a) HAAs and; b) meat mutagenicity, and the prevalence of colorectal adenomas among 342 patients undergoing a screening colonoscopy. Both Phase 1 and 2 examined potential gene-diet interactions between dietary HAAs and genetic factors relevant to the biotransformation of HAAs and DNA repair. Results: In Phase 1, an interaction was observed for dietary HAAs and NAT1 polymorphisms where a positive association between HAA intakes and bulky DNA adduct levels was found among those with the NAT1 slow acetylator genotype, hypothesized to confer a lower ability to biotransform HAAs. In Phase 2, polymorphisms in genes involved in the biotransformation of HAAs (CYP1B1 rs10012 and rs1056827) and DNA repair (XPC rs2228001) were found to determine colorectal adenoma risk. As well, gene-diet interactions were observed for dietary HAAs/meat mutagenicity exposures and polymorphisms in CYP1B1 and XPD (rs13181 and rs1799793). Overall, a higher risk of colorectal adenoma was observed with higher HAA and/or meat mutagenicity exposures among those with polymorphisms which confer a greater activity to biotransform HAAs and/or a lower ability to repair DNA. Conclusion: This research supports the contribution of dietary HAAs and genetic susceptibility to the risk of developing colorectal adenomas and highlighted bulky DNA adduct formation as a potential biologic pathway through which HAAs may influence cancer risk. / Thesis (Ph.D, Community Health & Epidemiology) -- Queen's University, 2014-04-25 11:32:30.392

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Made available in DSpace on 2014-10-09T12:35:46Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:03:54Z (GMT). No. of bitstreams: 0 / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP