Orientador: Carmem Silvia Fontanetti Christofoletti / Banca: Tatiana da Silva Souza / Banca: Ana Cristina Mielli / Resumo: O lodo de esgoto pode conter substâncias tóxicas, estar contaminado com metais pesados e até mesmo por compostos químicos persistentes, sendo assim, a disposição inadequada desse resíduo pode fazer tais poluentes retornarem ao ambiente e, eventualmente, entrar na cadeia alimentar, caso sejam absorvidos pelas plantas. O conhecimento dos agentes químicos presentes no lodo permite avaliar o risco de contaminação alimentar e ambiental decorrente da utilização de lodos como fertilizantes agrícolas, também chamados de biossólidos. Logo, o presente estudo teve por objetivo avaliar o potencial genotóxico, citotóxico e mutagênico do lodo gerado por uma Estação de Tratamento de Esgoto (ETE), por meio dos sistemas-teste Allium cepa e Tradescantia pallida. As coletas foram realizadas em abril de 2009 e maio de 2010 e os organismos foram expostos ao lodo bruto e seu solubilizado. Quando comparados os resultados obtidos nos bioensaios com as análises físico-químicas, não é possível estabelecer relação de causa e efeito com nenhum composto em específico, uma vez que todos os parâmetros avaliados se encontram dentro dos limites estabelecidos pela Resolução CONAMA 375; no entanto, em ambos os organismos, o lodo apresentou-se genotóxico e mutagênico, alertando sobre a necessidade de cuidado na disponibilização deste tipo de resíduo em solos. Dessa forma é possível concluir que os ensaios de toxicidade genética são capazes de identificar os efeitos diretos do lodo de esgoto e poderiam ser contemplados pela legislação como ferramenta complementar à bateria de testes já estabelecida devido à simplicidade dos testes e custo relativamente reduzido. O trabalho traz ainda uma revisão de literatura sobre a utilização da espécie Tradescantia, suas bases e aplicações das técnicas do pêlo estaminal (Trad-SHM) e teste o do micronúcleo (Trad- MCN), apontando suas... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Sewage sludge can contain toxic substances, may be contaminated with heavy metals and persistent chemicals, so the improper disposal of this waste can return such pollutants to the environment and possibly return to the food chain if absorbed by plants. The knowledge of chemical agents present in the sludge can assess the risk of food contamination and environmental arising from the use of sludge as agricultural fertilizer, also called biosolids. Therefore, this study aimed to evaluate the potential genotoxic, cytotoxic and mutagenic of sludge generated from a Wastewater Treatment Plant (WTP) by the Allium cepa and Tradescantia pallida tests-systems. Samples were collected in April 2009 and May 2010 and the organisms were exposed to raw sludge and its solublilizated samples. Comparing the results obtained in bioassays with the physico-chemical properties, its cannot establish cause and effect relationship with any compound in particular, since all parameters are within limits set by CONAMA Resolution 375, however, in both organisms, the sludge showed genotoxic and mutagenic, and warns about caution in providing this type of waste in soils. Thus, we conclude that the genetic toxicity tests are able to identify the direct effects of sewage sludge and could be provided by the law as a complementary tool to the battery of tests previously established, due to the simplicity of the tests and relatively low cost. The work also contains a review on the use of Tradescantia species, their bases and applications of the techniques of stamen hair (Trad-SHM) and the micronucleus test (Trad-MCN), pointing out its advantages as a tool for monitoring of environmental health / Mestre

Made available in DSpace on 2014-06-11T19:22:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-03-02Bitstream added on 2014-06-13T19:49:27Z : No. of bitstreams: 1 maziviero_gt_me_rcla.pdf: 2136084 bytes, checksum: f88fe503bcf92cfda47c9034c3c0d9c5 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O lodo de esgoto pode conter substâncias tóxicas, estar contaminado com metais pesados e até mesmo por compostos químicos persistentes, sendo assim, a disposição inadequada desse resíduo pode fazer tais poluentes retornarem ao ambiente e, eventualmente, entrar na cadeia alimentar, caso sejam absorvidos pelas plantas. O conhecimento dos agentes químicos presentes no lodo permite avaliar o risco de contaminação alimentar e ambiental decorrente da utilização de lodos como fertilizantes agrícolas, também chamados de biossólidos. Logo, o presente estudo teve por objetivo avaliar o potencial genotóxico, citotóxico e mutagênico do lodo gerado por uma Estação de Tratamento de Esgoto (ETE), por meio dos sistemas-teste Allium cepa e Tradescantia pallida. As coletas foram realizadas em abril de 2009 e maio de 2010 e os organismos foram expostos ao lodo bruto e seu solubilizado. Quando comparados os resultados obtidos nos bioensaios com as análises físico-químicas, não é possível estabelecer relação de causa e efeito com nenhum composto em específico, uma vez que todos os parâmetros avaliados se encontram dentro dos limites estabelecidos pela Resolução CONAMA 375; no entanto, em ambos os organismos, o lodo apresentou-se genotóxico e mutagênico, alertando sobre a necessidade de cuidado na disponibilização deste tipo de resíduo em solos. Dessa forma é possível concluir que os ensaios de toxicidade genética são capazes de identificar os efeitos diretos do lodo de esgoto e poderiam ser contemplados pela legislação como ferramenta complementar à bateria de testes já estabelecida devido à simplicidade dos testes e custo relativamente reduzido. O trabalho traz ainda uma revisão de literatura sobre a utilização da espécie Tradescantia, suas bases e aplicações das técnicas do pêlo estaminal (Trad-SHM) e teste o do micronúcleo (Trad- MCN), apontando suas... / Sewage sludge can contain toxic substances, may be contaminated with heavy metals and persistent chemicals, so the improper disposal of this waste can return such pollutants to the environment and possibly return to the food chain if absorbed by plants. The knowledge of chemical agents present in the sludge can assess the risk of food contamination and environmental arising from the use of sludge as agricultural fertilizer, also called biosolids. Therefore, this study aimed to evaluate the potential genotoxic, cytotoxic and mutagenic of sludge generated from a Wastewater Treatment Plant (WTP) by the Allium cepa and Tradescantia pallida tests-systems. Samples were collected in April 2009 and May 2010 and the organisms were exposed to raw sludge and its solublilizated samples. Comparing the results obtained in bioassays with the physico-chemical properties, its cannot establish cause and effect relationship with any compound in particular, since all parameters are within limits set by CONAMA Resolution 375, however, in both organisms, the sludge showed genotoxic and mutagenic, and warns about caution in providing this type of waste in soils. Thus, we conclude that the genetic toxicity tests are able to identify the direct effects of sewage sludge and could be provided by the law as a complementary tool to the battery of tests previously established, due to the simplicity of the tests and relatively low cost. The work also contains a review on the use of Tradescantia species, their bases and applications of the techniques of stamen hair (Trad-SHM) and the micronucleus test (Trad-MCN), pointing out its advantages as a tool for monitoring of environmental health

nÃo hà / O elevado consumo de pesticidas no Brasil e no mundo tem levado grupos de pesquisadores a relacionar essa exposiÃÃo a possÃveis danos genÃticos e agravos a saÃde do trabalhador rural. Estudos revelam que o cÃncer à considerado doenÃa genÃtica, vez que resulta do acÃmulo de mutaÃÃes em genes comprometidos com o controle da proliferaÃÃo e da diferenciaÃÃo celular ou de mutaÃÃes em genes envolvidos com os mecanismos de reparo do DNA. O objetivo dessa estudo foi realizar um biomonitoramento genÃtico em indivÃduos expostos ocupacionalmente a pesticidas avaliando a ocorrÃncias de danos cromossÃmicos, atravÃs do teste do MicronÃcleo em cÃlulas esfoliadas da mucosa bucal, teste Cometa e teste de AberraÃÃes CromossÃmicas em linfÃcitos de sangue perifÃrico. Como tambÃm alteraÃÃes hematolÃgicas e hepÃticas. A populaÃÃo estudada incluiu 32 agricultores moradores do povoado Vila Bessa, ConceiÃÃo do JacuÃpe, Bahia, expostos ocupacionalmente a pesticidas e 30 indivÃduos controle, sem historia de exposiÃÃo a pesticidas. O material para anÃlise do teste do micronÃcleo foi coletado por raspagem da mucosa bucal com escova cytobrush, confeccionado um esfregaÃo e posteriormente fixado em soluÃÃo de metanol/Ãcido acÃtico (3:1) e corados pelo mÃtodo FeÃlgen/Fast Green, as lÃminas foram analisadas em teste cego sob microscopia Ãptica em um mÃnimo de 1000 cÃlulas/indivÃduo. Para realizaÃÃo do teste Cometa e de AberraÃÃes, cromossÃmicas e das alteraÃÃes hematolÃgicas e hepÃticas foram coletadas 10 mL de sangue perifÃrico. O teste Cometa foi executado de acordo com a metodologia descrita por por Singh et al. (1988), foram contados 100 cometas por lÃmina e classificados, por anÃlise visual, dentre cinco categorias de danos (0, 1, 2, 3 e 4), e calculado o Ãndice e a FreqÃÃncia de dano. O teste de AberraÃÃes CromossÃmicas foi realizada atravÃs de culturas de linfÃcitos e obtenÃÃo de metÃfases pela interrupÃÃo da citocinese das cÃlulas. Foram analisados o hemograma, e as transaminases TGO, TGP E GGT que foram processados pelo laboratÃrio de anÃlise bioquÃmica de Escola Bahiana de Medicina e SaÃde PÃblica. NÃo houve diferenÃa significativa na ocorrÃncia de micronÃcleos entre os grupos avaliados (p = 0,163), mas alteraÃÃes nucleares indicativos de apoptose e necrose foram encontradas significantemente no grupo exposto a pesticidas (p = 0,001), indicando que uma maior injÃria celular do que simplesmente uma resposta a diferenciaÃÃo e maturaÃÃo do epitÃlio. AberraÃÃes CromossÃmicas numÃricas (3,3%) foi encontrada significantivamente para o grupo exposto (p = 0,001), foram encontrados danos ao DNA avaliados pelo teste Cometa no escore 1 (p< 0.001) no grupo exposto; alÃm do Ãndice de Dano cromossÃmico com mÃdia  SEM 4.032  0.3336 para o grupo controle e mÃdia  SEM 41.05  3.227 para o grupo exposto a pesticida (p<0,0001); e FreqÃÃncia de Dano: mÃdia  SEM grupo controle 4.081  0.3667 e mÃdia  SEM grupo exposto a pesticida 38.44  2.664, com diferenÃas significativas para o grupo exposto (p<0,0001). Os indivÃduos pesquisados estÃo expostos ao glifosato e ao paration-metÃlico, ambos tÃxicos para o organismo humano, e apresentavam-se anÃmicos (p=0,004) e com leucopenia (p < 0,001), porÃm sem alteraÃÃes nas avaliaÃÃes hepÃticas. ConcluÃmos que esses indivÃduos estÃo expostos a agentes potencialmente genotÃxicos, alÃm de apresentarem alteraÃÃes hematolÃgicas, e que a persistÃncia desse contato com os pesticidas poderà levar a desencadeamento dos fenÃmenos envolvidos na iniciaÃÃo e promoÃÃo do cÃncer. / The high consumption of pesticides in Brazil and all over the world have lead researches to relate this exposition to possible genetic and health damages in rural workers. Studies reveal that cancer is considered a genetic disease, once it results of the mutation accrual in genes involved with control of proliferation and cellular differentiation or mutations in genes involved with the DNA repair. The aim of this study was realize a genetic biomonitoring in individuals occupationally exposed to pesticides evaluating the occurrence of chromosomal damages, by the Micronucleus assay in exfoliated cells of buccal mucosa, Comet assay and Chromosome Aberration assay in peripheral blood lymphocytes. Hematologic and hepatic alterations were also evaluated. The studied population included 32 agriculturists living in the village of Vila Bessa, ConceiÃÃo do JacuÃpe, Bahia, occupationally exposed to pesticides, and 30 control individuals, with no history of pesticides exposition. For the micronucleus assay, the material was collected by scaling buccal mucosa with a cytobrush, the smear was made and then fixed in methanol/acetic acid solution (3:1) and colored by FeÃlgen/Fast Green Method, slides were analyzed in blind test by optic microscopy in a minimum of 1000 cells/individual. To realize the assay of Comet and Aberration, Chromosomal and hematologic and hepatic alterations, were collected 10 mL of peripheral blood. Comet test was made according the methodology described by Singh et al. (1988), were counted 100 comet by slides and classified, by visual analyses, into five categories of damages (0, 1, 2, 3 e 4), and then calculated the index and frequency of damage. Chromosome Aberration test was realized with a lymphocytes culture and obtaining of metaphases by interrupting the cells cytokinesis. The hemogram and the transaminases TGO, TGP and GGT were analyzed; those were processed by the biochemical analyses laboratory of Escola Bahiana de Medicina e SaÃde PÃblica. That wasnÂt statistical difference in the occurrence of micronucleus among the evaluated groups (p = 0.163), but nuclear alterations, indicative of apoptosis and necrosis, were significantly found in the pesticide exposed group (p = 0.001), indicating a major cellular injury than a simple answer to epitheliumÂs differentiation and maturation. Numeric Chromosome Aberrations (3.3%) were significantly found in the exposed group (p = 0.001), were found DNA damages evaluated by the Comet assay in score 1 (p<0.001) in the exposed group; as also index of chromosomal damage with media  SEM 4.032  0.3336 to the control group and media  41.05  3.227 to the pesticide exposed group (p<0.0001); and frequency of damage: media  SEM control group 4.081  0.3667 and media  SEM pesticide exposed group 38.44  2.664, with significant differences in the exposed group (p<0.0001). The studied individuals are exposed to glifosate and methyl parathion, both toxic to the human organism, and were anemics (p=0.004) and with leukopenia (p<0.001), however with no alterations in hepatic evaluations. We conclude that these individuals are exposed to potentially genotoxic agents, besides present hematologic alterations, and that the persistence of this contact with the pesticides can trigger to phenomenonâs involved with cancer initiation and promotion.

During the screening process 5,20 8 X chromosomes of -Drosophila melanogaster were analyzed for the presence of temperature-sensitive (ts) lethal mutations (i.e. mutants which die at 29°C but are viable at 22°C) in short proximal and distal segments of the chromosome. Seven ts and 16 non-ts lethals were recovered in both regions combined. A new class of mutations (class-3), which failed to survive at 29°C with either proximal or distal duplication and showed ts lethality with one, was found and extensively analyzed. These mutants were initially interpreted to be dominant ts's, although the heterozygotes of each mutant showed this not to be so. It was decided that these might more probably be chromosomes carrying a lethal mutation covered by the duplication, and a ts lethal mapping elsewhere. By masking the non-conditional lethal with a duplication, developmental studies of the ts mutant were made. The temperature-sensitive period (TSP) and lethal phase (LP) were characterized for each. All TSP’s spanned the early pupal interval, though an individual TSP might extend to either side of this interval. The pattern of temperature-sensitivity of C3-3 suggested that once formed at permissive temperature, its product was not affected by 29°C. The experiments suggest that the temperature-sensitive process occurs at transcription or translation. A lethal allele of the dor locus was recovered, and, in analysis of this mutant with other dor alleles and several variegating duplications, dor itself was found to be a ts lethal. "Warped" wing, a new phenotype of the dor locus which occurred only with the variegating duplications, was described. This paper further describes a method for developmental analysis of non-ts lethal mutations, involving the use of variegating rearrangements. / Science, Faculty of / Zoology, Department of / Graduate

The present study was initiated with the view of achieving two goals: 1) to establish a suitable genetic assay system for measuring the frequency of spontaneous and induced structural and numerical aberrations of autosomes during meiosis in females and 2) to provide a better understanding of the mechanisms responsible for the production of the aberrant classes recovered. By selective exclusion of all regular meiotic products this system enabled the recovery of large numbers of aberrant products. The multiplier system served as an internal dosimeter and provided an estimate of the population size from which the aberrancies arose which in turn provided a measure of the frequencies of each event. The four different classes of exceptional meiotic products were named according to the source or the structural nature of the chromosomes: reductional nondisjunction as "matroclinous"; equational nondisjunction as "equationals"; loss of chromosome 2 as "patroclinous"; and the attachment of homologous arms as "compounds". The results suggest that two main factors affect the recovery of induced aberrations: of most importance is isosequentiality and of lesser importance is genetic background. The three classes of simultaneously recovered progeny (excluding equational nondisjunctions) arise from a common mechanism of induction; a mechanism which also accounts for free arm formation. The location of the breaks, the position of the chromatids and the method of reconstitution determine the type of aberration produced. The reconstitution of these breaks in aberrant ways are referred to as interchanges. Furthermore, it would appear that the reconstitutions are restricted in that euchromatic breaks attach to euchromatic breaks and heterochromatic to heterochromatic. Interchanges resulting from breaks on opposite sides of the centromeres of homologues result in the formation of non-sister compound chromosomes and from breaks on opposite sides of the centromeres of sister chromatids result in the formation of sister compound chromosomes. The interchange, if between heterologues, could lead to the nondisjunction of a pair of chromosomes and be recovered, as in the present study, as matroclinous progeny. The reciprocal product of the interchange between heterologues would produce an equal number of nullo eggs observed as patroclinous progeny, but if the dyad so formed is heteromorphic, i.e. chromatids of different length, it would result in the greater recovery of patroclinous progeny because of the preferential inclusion of the shorter chromatid. The evidence for interchange mediated aberrations is provided by the recovery of free arms of chromosome 2. Experimental support for these events is provided by the unequivocal identification of the centromeres involved, which, as in this study, is made possible through the use of metacentric autosomes. / Science, Faculty of / Zoology, Department of / Graduate

Fan Chung-sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references. / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / List of Tables --- p.vii / List of Figures --- p.viii / List of Abbreviations --- p.x / Table of Contents --- p.xi / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Nasopharyngeal Carcinoma --- p.1-1 / Chapter 1.1.1 --- Histology of NPC --- p.1-1 / Chapter 1.1.2 --- Etiological Factors --- p.1-2 / Chapter 1.1.3 --- Genetic Changes in NPC --- p.1-5 / Chapter 1.2 --- Background of Present Study --- p.1-14 / Chapter 1.3 --- Aims of Study --- p.1-15 / Chapter Chapter 2 --- Comparative Genomic Hybridization and Fluorescence In- Situ Hybridization / Chapter 2.1 --- Introduction --- p.2-1 / Chapter 2.2 --- Fluorescence In-Situ Hybridization (FISH) --- p.2-2 / Chapter 2.2.1 --- Principle of FISH --- p.2-2 / Chapter 2.2.2 --- Applications of FISH --- p.2-2 / Chapter 2.2.3 --- Advantages and Limitations --- p.2-5 / Chapter 2.3 --- Comparative Genomic Hybridization (CGH) --- p.2-7 / Chapter 2.3.1 --- Principle of CGH --- p.2-7 / Chapter 2.3.2 --- Applications of CGH --- p.2-8 / Chapter 2.3.3 --- Advantages and Limitations --- p.2-10 / Chapter 2.4 --- Method of CGH --- p.2-13 / Chapter 2.4.1 --- CGH Probe Preparation --- p.2-13 / Chapter 2.4.2 --- CGH Template Preparation --- p.2-21 / Chapter 2.4.3 --- Hybridization --- p.2-23 / Chapter 2.4.4 --- Post-hybridization --- p.2-23 / Chapter 2.4.5 --- Fluorescence Detection --- p.2-24 / Chapter 2.4.6 --- Image Acquisition and Analysis --- p.2-24 / Chapter 2.5 --- Method of Interphase FISH --- p.2-29 / Chapter 2.5.1 --- FISH Probe Preparation --- p.2-29 / Chapter 2.5.2 --- FISH Template Preparation --- p.2-29 / Chapter 2.5.3 --- Hybridization --- p.2-30 / Chapter 2.5.4 --- Post-hybridization --- p.2-30 / Chapter 2.5.5 --- Fluorescence Detection --- p.2-30 / Chapter 2.5.6 --- Scoring of FISH Signals --- p.2-31 / Chapter 2.5.7 --- Threshold Determination --- p.2-31 / Chapter Chapter 3 --- FISH Studies on NPC Biopsies Guided by CGH Information Derived from Cell Lines and Xenografts / Chapter 3.1 --- Introduction --- p.3-1 / Chapter 3.2 --- Materials and Methods --- p.3-3 / Chapter 3.2.1 --- CGH Analysis --- p.3-3 / Chapter 3.2.2 --- Interphase FISH Analysis --- p.3-4 / Chapter 3.2.3 --- Statistical Analysis --- p.3-7 / Chapter 3.3 --- Results / Chapter 3.3.1 --- CGH --- p.3-9 / Chapter 3.3.2 --- Interphase FISH Analysis --- p.3-10 / Chapter 3.3.3 --- Statistical Analysis --- p.3-11 / Chapter 3.4 --- Discussion --- p.3-27 / Chapter 3.4.1 --- CGH --- p.3-27 / Chapter 3.4.2 --- Interphase FISH Analysis --- p.3-31 / Chapter 3.5 --- Summary of This Chapter --- p.3-36 / Chapter Chapter 4 --- CGH Studies on Universally Amplified DNA from Microdissected NPC Biopsies and Interphase FISH Analysis / Chapter 4.1 --- Introduction --- p.4-1 / Chapter 4.2 --- Materials and Methods --- p.4-4 / Chapter 4.2.1 --- CGH on Universally Amplified DNA --- p.4-4 / Chapter 4.2.2 --- Interphase FISH Analysis --- p.4-6 / Chapter 4.2.3 --- Statistical Analysis --- p.4-8 / Chapter 4.3 --- Results --- p.4-9 / Chapter 4.3.1 --- CGH on Universally Amplified DNA --- p.4-9 / Chapter 4.3.2 --- Interphase FISH Analysis --- p.4-10 / Chapter 4.3.3 --- Statistical Analysis --- p.4-11 / Chapter 4.3.4 --- Comparison of CGH and FISH Findings --- p.4-11 / Chapter 4.4 --- Discussions --- p.4-30 / Chapter 4.4.1 --- CGH Findings --- p.4-30 / Chapter 4.4.2 --- Interphase FISH Analysis --- p.4-41 / Chapter 4.4.3 --- Comparison of CGH and FISH Findings --- p.4-43 / Chapter 4.5 --- Summary of This Chapter --- p.4-45 / Chapter Chapter 5 --- Conclusion and Further Studies / Chapter 5.1 --- Conclusion --- p.5-1 / Chapter 5.2 --- Further Studies --- p.5-3 / Chapter 5.2.1 --- Combination of Microdissection --- p.5-3 / Chapter 5.2.2 --- Multicolor Karyotyping --- p.5-3 / Chapter 5.2.3 --- Microarrays --- p.5-4 / References --- p.R-1

by Angela Bik-Yu Hui. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 119-133). / Acknowledgements / Table of Contents / List of Tables / List of Figures / Abstract / Chapter CHAPTER 1 --- LITERATURE REVIEW --- p.1 / Chapter I. --- Nasopharyngeal carcinoma --- p.1 / Chapter II. --- Etiology of NPC --- p.3 / Chapter II a. --- Geographical & Environmental factors --- p.3 / Chapter II b. --- Epstein-Barr virus Infection --- p.5 / Chapter II c. --- Genetic Factors --- p.8 / Chapter III. --- Cytogenetic Studies of NPC --- p.10 / Chapter III a. --- Traditional Cytogenetics --- p.10 / Chapter III b. --- Previous cytogenetic findings of NPC --- p.12 / Chapter III.c. --- Fluorescence in-situ hybridization --- p.15 / Chapter III.d. --- The new NPC cell line: Cell-666 --- p.18 / Chapter IV. --- Molecular Genetic Studies in NPC --- p.19 / Chapter IV a. --- Oncogenes --- p.20 / Chapter IV b. --- Tumor suppresser genes (TSGs) --- p.22 / Chapter IV c. --- Loss of Heterozygosity Studies --- p.29 / Chapter IV d. --- LOH on Chromosome 11 --- p.32 / Chapter IV e. --- ATM Gene --- p.35 / Chapter CHAPTER 2 --- OBJECTIVE OF STUDY --- p.38 / Chapter CHAPTER 3 --- MATERIALS AND METHODS --- p.41 / Chapter I： --- Study of loss of heterozygosity on chromosome 11 --- p.41 / Chapter I a. --- Patients and Specimens --- p.41 / Chapter I.b. --- DNA extraction --- p.45 / Chapter I c. --- Microsatellite Polymorphism Analysis --- p.47 / Chapter I d. --- Multiplex PCR analysis --- p.52 / Chapter II. --- Cytogenetic Studies --- p.54 / Chapter II a. --- Culture of cell-666 --- p.54 / Chapter II b. --- Cytogenetic Analysis --- p.56 / Chapter II c. --- Fluorescence in-situ hybridization (FISH) --- p.58 / Chapter II d. --- FISH analysis of other NPC cell lines) --- p.62 / Chapter CHAPTER 4 --- RESULTS --- p.63 / Chapter I: --- Study of loss of heterozygosity on chromosome 11 --- p.63 / Chapter I a. --- LOH analysis --- p.63 / Chapter I b. --- Regions with L OH --- p.73 / Chapter I c. --- Multiplex PCR analysis --- p.79 / Chapter II: --- Cytogenetic Study --- p.83 / Chapter II a. --- Cytogenetic analysis of cell-666 --- p.83 / Chapter II.b. --- Fluorescence in-situ Hybridization (FISH) --- p.91 / Chapter CHAPTER 5 --- DTSCUSSION --- p.102 / Chapter I. --- LOH of Chromosome 11 Studies --- p.102 / Chapter II. --- Comparison with LOH studies of other chromosomes --- p.110 / Chapter III. --- Cytogenetic Studies --- p.113 / REFERENCES --- p.119

Thesis--University of Turku, 1984. / At head of title: From the Institute of Dentistry and the Institute of Biomedicine, University of Turku. Extra t.p. with thesis statement inserted. Also published in: Proceedings of the Finnish Dental Society, Vol. 80, 1984, Suppl. V. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 117-143).

Thesis--Copenhagen University. / Summary in Danish. Bibliography: p. 125-129.