A corrosão dos aparelhos ortodônticos pode induzir uma resposta inflamatória e causar alterações nos tecidos bucais de pacientes em tratamento. Portanto, o objetivo deste estudo foi avaliar os efeitos citogenéticos causados em células epiteliais bucais de pacientes submetidos a tratamento ortodôntico corretivo e compará-los a um grupo controle sem tratamento. Setenta e quatro (74) pacientes em tratamento ortodôntico corretivo e vinte e um (21) pacientes controle com idades entre 11 e 35 anos participaram da pesquisa, de ambos os gêneros e que estavam em atendimento na clínica de pós-graduação em Ortodontia da Faculdade de Odontologia, Ribeirão Preto-USP. Os pacientes em tratamento foram divididos em quatro grupos que se diferenciaram pelo tempo de tratamento G1, n= 21 (1 mês a 12 meses de tratamento), G2, n= 21 (13 a 24 meses), G3, n= 23 (25 a 48 meses de tratamento) e G4, n=9 (acima de 48 meses de tratamento). As células foram coletadas por raspagem leve da parte interna da bochecha, com escova de dente e posteriormente colocadas em tubos de polietileno contendo soro fisiológico. Imediatamente após a obtenção da amostra foi realizada a avaliação dos danos citogenéticos por meio do teste de micronúcleos (MNT). Análises bivariadas foram realizadas nos dados obtidos utilizando testes paramétricos (Teste t, ANOVA) e testes não paramétricos quando necessário (teste do qui-quadrado ou exato e teste Kruskall Wallis seguido do teste de pós-teste de Dunn). Não foram encontradas diferenças estatisticamente significantes para nenhuma das anomalias citogenéticas, exceto para a \"cariolíticas\" que foi maior no grupo controle. Concluiu-se que não foram encontrados danos estatisticamente significantes, sendo o tratamento ortodôntico seguro em pacientes saudáveis com capacidade de reparo normal. / The corrosion of orthodontic appliances can induce an inflammatory response and cause changes in bucal tissues from patients undergoing treatment. Therefore, the aim of this study was to evaluate the cytogenetic damage in bucal epithelial cells of patients undergoing corrective orthodontic treatment and compare them to a control group without orthodontic treatment. Seventy-four (74) patients in orthodontic treatment and twenty-one (21) control individuals aged between 11 and 35 years participated in the research, of both genders and who were in attending at the clinic graduate in Orthodontics at Faculty of Dentistry, Ribeirão Preto-USP. The patients were divided into four treatment groups by treatment time; G1, n= 21 (1 month to 12 months of treatment), G2, n = 21 (13 to 24 months), G3, n = 23 (25 to 48 months of treatment) and G4, n = 9 (over 48 months of treatment). The cells were collected by gentle scraping with a toothbrush of the inside of the cheek and later placed in polyethylene tubes containing Physiological saline. Immediately after, the samples were evaluated for cytogenetic damage through the micronucleus test (MNT). Bivariate analyzes were performed using parametric tests (t test, ANOVA) and nonparametric tests when necessary (chi-square test or Kruskal Wallis test accurate and followed by Dunn test posttest). Thus, there wasn`t significant differences for any of the cytogenetic abnormalities except for karyolysis which was higher in the control group. It was concluded that statistically significant damage were not found, and orthodontic treatment is safe in healthy patients with repair capacity.

A crescente incidência da obesidade e suas comorbidades constituem-se em um grande desafio para a saúde no mundo. Além da doença cardiovascular e do diabetes, dados epidemiológicos demonstraram ligação entre a obesidade e diversos tipos de câncer. As alterações citogenéticas tem sido utilizadas como biomarcadores para identificação de danos celulares. Este estudo teve como objetivos: comparar a frequência dos tipos celulares (células basais e diferenciadas), anormalidades nucleares (células binucleadas, picnóticas, cariorréticas, cariolíticas e com cromatina condensada) e de danos celulares (micronúcleos e brotos nucleares) de células bucais esfoliadas em um grupo de obesos (teste) e em um grupo de indivíduos com peso normal (controle). A amostra foi composta por 30 indivíduos, sendo o grupo teste constituído por indivíduos obesos mórbidos (n=15) e o grupo controle por indivíduos com peso normal (n=15). A classificação do peso corporal foi feita de acordo com o Índice de Massa Corporal (IMC); um questionário forneceu informações sobre exposições ocupacionais e não ocupacionais; hábitos e dieta. As células da mucosa bucal foram coletadas da mucosa jugal, de ambos os lados, processadas e analisadas microscopicamente. Para cada indivíduo foram avaliadas 1000 células para a caracterização dos tipos celulares (basal e diferenciada) e alterações nucleares (células binucleadas, picnose, cariólise, cariorrexe, cromatina condensada) e 2000 células diferenciadas para verificar a presença de danos celulares (micronúcleos e brotos nucleares). Os dados foram processados e analisados estatisticamente, por meio do teste de Mann Whitney. Considerou-se o nível de significância de 5% (p<0,05). Observaram-se diferenças nas frequências de tipos celulares e anomalias nucleares para os dois grupos, porém estas diferenças não foram significativas (p>0,05). Quanto ao tipo de dano celular, notou-se a mesma frequência de brotos nucleares para ambos os grupos, entretanto, a frequência de micronúcleos foi maior para o grupo obeso (p<0,001). Neste estudo, verificou-se maior frequência de micronúcleos nas células esfoliadas da mucosa bucal em indivíduos obesos mórbidos que em indivíduos com peso normal. Este achado sugere que a obesidade possa levar à maior ocorrência de alterações citogenéticas. / The increasing incidence of obesity and its co-morbid conditions poses a great challenge to global health. In addition to cardiovascular disease and diabetes, epidemiological data demonstrate a link between obesity and multiple types of cancer. The buccal micronucleus cytome assay has been used as a biomarker for identification of cell damage. This study aimed to compare the frequency of cell types (basal and differentiated), nuclear anomalies (binucleated, pyknotic, karyorrhectic, karyolitic and condensed chromatin cells), and cell damage (micronuclei and nuclear buds) in exfoliated buccal cells in a group of obese (test) and a group of normal weight (control).The sample consisted of 30 subjects, the test group comprised of individuals with morbid obesity (n = 15) and a control group of normal weight (n = 15). The classification of body weight was made according to Body Mass Index (BMI), a questionnaire provided information on occupational exposures and non-occupational, lifestyle and diet. The oral mucosa cells were collected from the buccal mucosa, on both sides, processed and analyzed microscopically. For each individual 1000 cells were evaluated for the characterization of cell types (basal and differentiated) and nuclear abnormalities (binucleated cells, pyknosis, karyolysis, karyorrhexis, condensed chromatin) and 2000 differentiated cells for the presence of cellular damage (micronuclei and nuclear buds). The data were processed and statistically analyzed using the Mann-Whitney test. We considered the significance level of 5% (p <0.05). Differences were observed in the frequencies of cell types and nuclear abnormalities in both groups, but these differences were not significant (p> 0.05). Regarding the type of cell damage, we noticed the same frequency of nuclear buds for both groups, however, the frequency of micronuclei was higher in the obese group (p <0.001). In this study, there was a higher frequency of micronuclei in exfoliated cells of buccal mucosa in morbidly obese individuals than in individuals with normal weight. This finding suggests that obesity may lead to higher rates of cytogenetic changes.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Os carcinomas espinocelulares sÃo responsÃveis por mais de 90% das neoplasias malignas que ocorrem na mucosa bucal e tÃm como principal fator de risco o uso crÃnico do tabaco sob suas diversas formas. Comprovadamente o tabaco industrializado contÃm inÃmeros carcinÃgenos capazes de causar dano cromossÃmico. Para detectar o dano inicial na mucosa bucal de fumantes foi utilizado o ensaio do MicronÃcleo (MN) em cÃlulas esfoliadas por ser um teste simples, rÃpido, de baixo custo e que utiliza tÃcnica nÃo invasiva. Com o objetivo de estabelecer um teste de triagem para monitorar pacientes fumantes sob risco de desenvolver carcinoma bucal foram avaliadas as freqÃÃncias dos micronÃcleos e de outras alteraÃÃes nucleares em esfregaÃos de mucosa bucal, utilizando o protocolo adaptado ao de Tolbert et al. (1991). Foram analisados os micronÃcleos (MNs), as binucleaÃÃes e outras alteraÃÃes nucleares indicativas de citotoxicidade e genotoxicidade como cariorrÃxis, cariÃlise, cromatina condensada, picnose, falso micronÃcleo, broken-eggs e vacÃolos nucleares. Foi realizada uma comparaÃÃo intra-individual da regiÃo perifÃrica ao tumor (L) e da mucosa do lado oposto (LOL) dos pacientes com carcinoma e outra comparaÃÃo caracterizada como interindividual, pois comparou indivÃduos sadios (controle) e pacientes portadores de carcinomas bucais. Observou-se que a mucosa do lado oposto à lesÃo (LOL) possui alteraÃÃes nucleares que a caracterizam como mucosa nÃo sadia e que a alteraÃÃo tipo cariorrÃxis demonstrou ser melhor biomarcador para o LOL. AtravÃs da curva âROCâ foram verificados os valores de prediÃÃo das alteraÃÃes nucleares estatisticamente significativas resultantes da comparaÃÃo entre sadios e portadores de cÃncer bucal. A alteraÃÃo nuclear cariorrÃxis foi a que obteve maior sensibilidade (80%) e especificidade (80%). A associaÃÃo entre as alteraÃÃes nucleares preditoras de lesÃo maligna e fatores de risco demonstrou resultados mais fortemente significativos para o tabagismo (p<0,001). Neste estudo os micronÃcleos e as alteraÃÃes nucleares cariorrÃxis, cariÃlise, binucleaÃÃes e vacÃolos nucleares foram vÃlidas como preditoras para carcinoma bucal. / Squamous cells carcinomas are responsible for more than 90% of all cancer in the mucosa membranes of the mouth and the principal risk factor responsible is tobacco use. Certainly industrialized tobacco contains a lot of carcinogens able to cause chromosome breakage. The Micronucleus Assay in exfoliated cells was used to detect this initial breakage. It is simple, practical, inexpensive and non invasive technique. The objective of this study is to establish a trial text to monitoring smokers with risk to develop oral carcinoma. Epithelial smears was examined following the criteria described by Tolbert et al. (1991), micronucleus, binucleation and the cells presenting degenerative phenomena, indicative of cytotoxicity and genotoxicity sush as karyorrhexis, karyolysis, pycnosis, condensed cromatin, buds, broken-eggs, and nuclear vacuoles were analyzed. An intra-individual comparison was realized in patients with cancer (periphery of malign lesion and opposite side of lesion) another comparison characterized as interidividual compared healthy people (control group) and patients with oral carcinomas. The study showed that the side opposite of lesion (LOL) is non health mucosa and karyorrhexis is the best biomarker in this side. The specificity and sensibility of nuclear alterations was analyzed using ROC curve. The results show that karyorrhexis is the better specificity (80%) and sensibility (80%) all of them. The association between the nuclear alterations and risk factors show a higher significant statistical for tobacco use (p<0,001). In this study micronucleus, karyorrhexis, karyolysis, binucleation and nuclear vacuoles are valid to predict oral carcinoma.

Nestas últimas décadas, investigações sobre compostos naturais, efetivos, não tóxicos, com potencial radioprotetor vêm despertando um grande interesse em consonância com a utilização crescente de vários tipos de radiação ionizante nas mais diversas finalidades. Entre eles a própolis uma resina coletada pelas abelhas (Apis mellifera), vem sendo apontada como promissora por apresentar uma série de características biológicas vantajosas, por exemplo, anti-inflamatória, antimicrobiana, antitumoral, imunomoduladora, antioxidante e também scavenger de radicais livres. O presente estudo teve como objetivo principal, averiguar efeito da própolis brasileira procedente de Rio Grande do Sul (AF 08) em células de ovário de hamster Chinês (CHO-K1) e em células tumorais de próstata (PC3), irradiadas com 60Co. Para tanto, foram utilizados três principais parâmetros interligados entre si: indução de micronúcleo, viabilidade celular e morte clonogênica. A escolha destes parâmetros se justifica pelo seu significado biológico, além do fato de serem prontamente observáveis e mensuráveis em células irradiadas. Os dados citogenéticos obtidos, mostraram um efeito radioprotetor da própolis (5 - 100 &mu;g/ml) na indução de dano ao DNA em ambas as linhagens celulares, irradiadas com doses de 1 - 4 Gy. No entanto, o ensaio de citotoxicidade mostrou um efeito antiproliferativo pronunciado da própolis (50 - 400 &mu;g/ml) em células PC3 irradiadas com 5 Gy. As curvas de sobrevida obtidas foram ajustadas satisfatoriamente pelo modelo linear-quadrático, cujo componente foi mais alto em células CHO-K1. Quanto à capacidade clonogênica, as células PC3 mostraram-se mais radiossensíveis que as células CHO-K1 nas doses mais altas da curva de sobrevida. A própolis, nas concentrações de 30 - 100 &mu;g/ml, não influenciou no potencial clonogênico das células PC3, visto que, as curvas de sobrevida associadas ou não com a própolis, mostraram perfis similares, ao passo que o tratamento combinado em células CHO-K1 exibiu um efeito estimulador da proliferação. Os dados obtidos in vitro mostraram um potencial uso da própolis AF-08, como uma substância natural e não tóxica, na prevenção contra os efeitos danosos da radiação ionizante, nas doses e nas concentrações analisadas. / In the last decades, it has been given a great interest to investigations concerning natural, effective, nontoxic compounds with radioprotective potential together with the increasing utilization of different types of ionizing radiation for various applications. Among them propolis, a resinous compound produced by honeybees (Apis mellifera), has been considered quite promising, since it presents several advantageous biological characteristics, i. e., anti-inflammatory, antimicrobial, anticarcinogenic, antioxidant and also free radical scavenging action. The purpose of the present study was to evaluate the effect of Brazilian propolis, collected in the State of Rio Grande do Sul, on Chinese hamster ovary (CHO-K1) and human prostate cancer (PC3) cells, irradiated with 60Co radiation. For this purpose, three interlinked parameters were analyzed: micronucleus induction, cell viability and clonogenic death. The choice of these parameters was justified by their biological significance, in addition to the fact that they are readily observable and measurable in irradiated cells. The cytogenetic data obtained showed a radioprotective effect of propolis (5-100 &mu;g/ml) in the induction of DNA damage for both cell lines, irradiated with doses of 1 - 4 Gy. The cytotoxicity assay, however, showed a prominent antiproliferative effect of propolis (50 - 400 &mu;g/ml) in PC3 cells irradiated with 5 Gy. The survival curves obtained were adequately fitted by a linear-quadratic model, where the coefficient was higher in CHO-K1 cells. Concerning the clonogenic capacity, PC3 cells were more radiosensitive than CHO-K1 cells at the higher doses of the survival curve. Propolis at the concentrations of 30 - 100 &mu;g/ml, did not influence the clonogenic potential of PC3 cells, since the survival curves, associated or not with propolis, were found similar, although the combined treatment in CHO-K1 cells exhibited a stimulating proliferative effect. The data obtained in vitro showed a potential use of propolis AF-08, a natural and nontoxic compound, in the prevention against the adverse effect of ionizing radiation, at the doses and concentrations here analyzed.

A crescente incidência da obesidade e suas comorbidades constituem-se em um grande desafio para a saúde no mundo. Além da doença cardiovascular e do diabetes, dados epidemiológicos demonstraram ligação entre a obesidade e diversos tipos de câncer. As alterações citogenéticas tem sido utilizadas como biomarcadores para identificação de danos celulares. Este estudo teve como objetivos: comparar a frequência dos tipos celulares (células basais e diferenciadas), anormalidades nucleares (células binucleadas, picnóticas, cariorréticas, cariolíticas e com cromatina condensada) e de danos celulares (micronúcleos e brotos nucleares) de células bucais esfoliadas em um grupo de obesos (teste) e em um grupo de indivíduos com peso normal (controle). A amostra foi composta por 30 indivíduos, sendo o grupo teste constituído por indivíduos obesos mórbidos (n=15) e o grupo controle por indivíduos com peso normal (n=15). A classificação do peso corporal foi feita de acordo com o Índice de Massa Corporal (IMC); um questionário forneceu informações sobre exposições ocupacionais e não ocupacionais; hábitos e dieta. As células da mucosa bucal foram coletadas da mucosa jugal, de ambos os lados, processadas e analisadas microscopicamente. Para cada indivíduo foram avaliadas 1000 células para a caracterização dos tipos celulares (basal e diferenciada) e alterações nucleares (células binucleadas, picnose, cariólise, cariorrexe, cromatina condensada) e 2000 células diferenciadas para verificar a presença de danos celulares (micronúcleos e brotos nucleares). Os dados foram processados e analisados estatisticamente, por meio do teste de Mann Whitney. Considerou-se o nível de significância de 5% (p<0,05). Observaram-se diferenças nas frequências de tipos celulares e anomalias nucleares para os dois grupos, porém estas diferenças não foram significativas (p>0,05). Quanto ao tipo de dano celular, notou-se a mesma frequência de brotos nucleares para ambos os grupos, entretanto, a frequência de micronúcleos foi maior para o grupo obeso (p<0,001). Neste estudo, verificou-se maior frequência de micronúcleos nas células esfoliadas da mucosa bucal em indivíduos obesos mórbidos que em indivíduos com peso normal. Este achado sugere que a obesidade possa levar à maior ocorrência de alterações citogenéticas. / The increasing incidence of obesity and its co-morbid conditions poses a great challenge to global health. In addition to cardiovascular disease and diabetes, epidemiological data demonstrate a link between obesity and multiple types of cancer. The buccal micronucleus cytome assay has been used as a biomarker for identification of cell damage. This study aimed to compare the frequency of cell types (basal and differentiated), nuclear anomalies (binucleated, pyknotic, karyorrhectic, karyolitic and condensed chromatin cells), and cell damage (micronuclei and nuclear buds) in exfoliated buccal cells in a group of obese (test) and a group of normal weight (control).The sample consisted of 30 subjects, the test group comprised of individuals with morbid obesity (n = 15) and a control group of normal weight (n = 15). The classification of body weight was made according to Body Mass Index (BMI), a questionnaire provided information on occupational exposures and non-occupational, lifestyle and diet. The oral mucosa cells were collected from the buccal mucosa, on both sides, processed and analyzed microscopically. For each individual 1000 cells were evaluated for the characterization of cell types (basal and differentiated) and nuclear abnormalities (binucleated cells, pyknosis, karyolysis, karyorrhexis, condensed chromatin) and 2000 differentiated cells for the presence of cellular damage (micronuclei and nuclear buds). The data were processed and statistically analyzed using the Mann-Whitney test. We considered the significance level of 5% (p <0.05). Differences were observed in the frequencies of cell types and nuclear abnormalities in both groups, but these differences were not significant (p> 0.05). Regarding the type of cell damage, we noticed the same frequency of nuclear buds for both groups, however, the frequency of micronuclei was higher in the obese group (p <0.001). In this study, there was a higher frequency of micronuclei in exfoliated cells of buccal mucosa in morbidly obese individuals than in individuals with normal weight. This finding suggests that obesity may lead to higher rates of cytogenetic changes.

Submitted by admin tede (tede@pucgoias.edu.br) on 2018-04-19T11:44:34Z No. of bitstreams: 1 CLÁUDIA RACHID COSTA.pdf: 740066 bytes, checksum: 10863a04e188cbf0c2ad0d2d4fd873fd (MD5) / Made available in DSpace on 2018-04-19T11:44:34Z (GMT). No. of bitstreams: 1 CLÁUDIA RACHID COSTA.pdf: 740066 bytes, checksum: 10863a04e188cbf0c2ad0d2d4fd873fd (MD5) Previous issue date: 2018-04-19 / The malignant neoplasms are a public health problem worldwide, being the biggest cause of premature mortality of the planet. In Brazil, in 2012, more than 200 thousand people died, and it is estimated that within 20 years, there will be an increase of approximately 70% of new cases. Therefore, since a long time, the alternative therapies constitute a way of promoting "miracle" for the cure of cancer. However, the miraculous empiricism has no scientific basis and not enough documentation to prove the efficacy and quality these substances used in this self-treatment. Thus, the fosfoetanolamina, an experimental substance caused a great international repercussion and expos Brazil to an embarrassing situation. A governmental law, imposed the use of synthetic fosfoetanolamina for cancer treatment, without scientific bases for the confirmation of the effects and efficacy of anticancer treatment, by means of experimental laboratory studies and clinical trials. Thus the objective of this work was to evaluate the angiogenic activity/Antiangiogenic, mutagênica/antimutagênica this substance. The test of angiogenesis was performed using an experimental model (MCA) corioalantóide membrane of chicken egg. While the tests for mutagenicity and antimutagenicity, were performed by a micronucleus test in mouse bone marrow. The results were significant in all tests performed. / As neoplasias malignas são um problema de saúde pública mundial, sendo a maior causa de mortalidade prematura do planeta. No Brasil, em 2012, mais de 200 mil pessoas foram a óbito, e estima-se que num prazo de 20 anos, haverá aumento de cerca de 70% de novos casos. Por isso, desde muito tempo, as terapias alternativas constituem uma forma de promover o "milagre" para a cura do câncer. Contudo, o empirismo milagroso não tem base científica e nem documentação suficiente para comprovar a eficácia e qualidade destas substancias utilizadas neste autotratamento. Assim sendo, a fosfoetanolamina, uma substância experimental causou uma grande repercussão internacional e expos o Brasil a uma situação embaraçosa. Uma lei governamental, impôs a utilização da fosfoetanolamina sintética para o tratamento do câncer, sem bases científicas para a confirmação dos efeitos e eficácia do tratamento anticâncer, por meio de estudos laboratoriais experimentais e ensaios clínicos. Assim o objetivo deste trabalho, foi avaliar as atividades angiogênica/antiangiogênica, mutagênica/antimutagênica desta substância. O teste de angiogênese foi realizado através do modelo experimental em membrana corioalantóide (MCA) de ovo de galinha. Enquanto os testes de mutagenicidade e antimutagenicidade, foram realizados pelo Teste de Micronúcleo em medula óssea de camundongo. Os resultados foram significativos em todos os testes realizados.

Submitted by Ricardo Cedraz Duque Moliterno (ricardo.moliterno@uefs.br) on 2015-08-07T01:02:49Z No. of bitstreams: 1 DISSERTA??O- LEONARDO DA CUNHA MENEZES SOUZA.pdf: 2029455 bytes, checksum: 2374a0c5996ead5ddad034150d2e36b7 (MD5) / Made available in DSpace on 2015-08-07T01:02:49Z (GMT). No. of bitstreams: 1 DISSERTA??O- LEONARDO DA CUNHA MENEZES SOUZA.pdf: 2029455 bytes, checksum: 2374a0c5996ead5ddad034150d2e36b7 (MD5) Previous issue date: 2013-09-30 / Funda??o de Amparo ? Pesquisa do Estado da Bahia - FAPEB / The use of anabolic androgenic steroids (AAS) has grown among practitioners of recreational bodybuilding, with significant contributions of "Designer Steroids" (DS), EAA designed aiming muscle hypertrophy in healthy subjects. The abusive use of AAS in general is associated with adverse effects, one of the most worrisome is cancer development. Given that cancer is a genetic disease resulting from changes in genes critical in maintaining genomic stability and in the control of proliferation and differentiation, biomarkers able to identify these changes can take predictive value and contribute to reducing the high rates of morbidity and mortality by this disease. The aim of this study was to evaluate the effectiveness of the Cytokinesis Block Micronucleus Test (CBMN) in human lymphocytes in identifying risk groups for cancer development in users of AAS. Was collected 5ml of blood from 15 AAS users bodybuilders (G1), 20 nonusers bodybuilders (G2) and 20 nonusers sedentary (G3). Lymphocytes were cultured with blocking of cytokinesis and subsequent processing for making slides. MN analysis was performed on a minimum of 1000 binucleated lymphocytes. The occurrence of MN was significantly higher (p <0.05) in individuals of G1 compared to G2 and G3. The results indicate the sensitivity of CBMN in human lymphocytes in the identification of chromosomal damage in consequence of AAS using, however, further studies are needed to determine their potential to predict the cancer risk in users of AAS. / O uso de esteroides anabolizantes androg?nicos (EAA) tem crescido entre praticantes recreativos de muscula??o, com contribui??es significativas dos Designer Steroids (DS), EAA projetados para fins de hipertrofia muscular em indiv?duos saud?veis. O uso abusivo de EAA em geral est? associado a efeitos adversos, sendo um dos mais preocupantes o desenvolvimento de c?ncer. Tendo em vista que o c?ncer ? uma doen?a gen?tica resultante de altera??es em genes cr?ticos na manuten??o da estabilidade gen?mica e do controle da prolifera??o e diferencia??o, biomarcadores capazes de identificar estas altera??es podem assumir valor preditivo e contribuir para diminui??o das altas taxas de morbidade e mortalidade por esta doen?a. O objetivo deste estudo foi avaliar a efic?cia do Teste de Micron?cleo com Bloqueio da Citocinese (MNCtB) em linf?citos humanos na identifica??o de grupos de risco para o desenvolvimento de c?ncer em usu?rios de EAA. Foram coletados 5ml de sangue de 15 usu?rios de EAA praticantes de muscula??o (Grupo I), 20 n?o usu?rios praticantes de muscula??o (Grupo II) e 20 n?o usu?rios sedent?rios (Grupo III). Foi realizada cultura de linf?citos com o bloqueio da citocinese e posterior processamento para confec??o de l?minas. A an?lise de MN foi realizada em um m?nimo de 1000 linf?citos binucleados. A ocorr?ncia de MN foi significativamente maior (p<0,05) nos indiv?duos do Grupo I comparados aos do Grupo II e Grupo III. Os resultados apontam para a sensibilidade do MNCtB na identifica??o de danos cromoss?micos decorrentes do uso de EAA. Estudos subsequentes para determinar seu potencial preditivo para o risco de c?ncer em usu?rios de EAA s?o necess?rios.

Einleitung: Methylphenidat (MPH) als Medikament der ersten Wahl bei Patienten mit einem Aufmerksamkeitsdefizit- /Hyperaktivitätssyndrom (ADHS) ist für die Therapie von Kindern aber auch von Erwachsenen weit verbreitet. Weil es immer noch Sicherheitsbedenken gegen dieses Medikament gibt, wurde in der vorliegenden Studie untersucht, ob die Langzeiteinnahme von MPH unschädlich hinsichtlich eines zytogenetischen Effektes ist. Ein weiteres Ziel war die Beurteilung von chronischer psychosozialer Stressbelastung von Patienten im Vergleich zu Kontrollprobanden und zu beurteilen ob die Medikation einen Einfluss auf die Höhe des Stresses hat. Nicht zuletzt war das dritte Ziel der Studie zu untersuchen, ob Stress selbst zu zytogenetischen Schäden führt. Material und Methoden: Lymphozyten von 72 (42 ADHS- und 28 gesunde Kontrollprobanden) geschlechts- und altersgematchte Probanden im Alter von 18-28 Jahren, wurden aus venösem Blut für den Mikronukleusassay isoliert. Hauptendpunkt der Studie war die Mikrokernanzahl in binukleären Zellen. Die psychosoziale Stressbelastung der letzten drei Monate wurde mit dem Trier Inventar zum chronischen Stress (TICS) gemessen. Zusätzlich wurden Speichelproben für eine Cortisolmessung gesammelt. Ergebnisse: Ein Einfluss der MPH-Einnahme auf die Mikrokernfrequenz konnte nicht gefunden. ADHS-Patienten wiesen eine signifikant höhere Stressbelastung im Vergleich zu den Kontrollprobanden auf. Ein signifikanter positiver Einfluss auf das chronische Stresserleben unter MPH-Einnahme konnte bei Einnahme von mehr als 1 Jahr beobachtet werden. Die Stressbelastung der ADHS-Patienten und Kontrollprobanden zeigte keine Korrelation zu zytogenetischen Endpunkten. Eine kleine Untergruppe, ADHS-Patienten mit Komorbidität Depression, zeigte jedoch signifikante erhöhte Mikrokernfrequenzanzahlen unter stark erhöhtem chronischen Stress. Aussichten: Aus unserer Sicht kann MPH auch in der Langzeittherapie sicher hinsichtlich eines Krebsrisikos in gewichts- und symptomadaptierter Dosis eingesetzt werden. Weitere Studien sind nötig um das Krebsrisiko bei chronischer erhöhter Stressbelastung abzuschätzen. / Introduction: Methylphenidate (MPH) as first line treatment for patients with attention deficit hyperactivity disorder (ADHD) is widely used not only for therapy in children but also in adults. Because there are still safety concerns for this medication this study investigated if the long term treatment of MPH is harmless regarding to cytogenetic effects. A further aim was to compare the psychosocial stress levels of ADHD patients to those in control subjects and to investigate if MPH medication has an influence on self-perceived stress levels in ADHD. The third aim of this study was to explore if psychosocial stress leads to cytogenetic damage. Materials and methods: Lymphocytes of 72 subjects (42 ADHD and 28 healthy control subjects), matched in age and gender(aged 18-28 years) were isolated from venous blood for micronucleus assay. Main endpoint was the micronucleus frequency in binucleated cells. Psychosocial stress exposure of the last three month was measured by Trier Inventory for Chronic Stress (TICS). Additionally saliva samples were collected for cortisol measurement. Results: An influence of MPH intake on cytogenetic markers could not be found. ADHD patients showed significantly higher stress levels in comparison to control subjects. Patients taking MPH for more than one year displayed significantly lower chronic psychosocial stress levels than patients taking it less than one year or not-treated patients. Stress exposure of ADHD patients and control subjects showed no correlations to cytogenetic endpoints. A small subgroup of ADHD patients with comorbid depression showed significantly higher micronuclei frequencies and reported greater increased chronic stress. Views: We conclude that MPH in weight - and symptom - adjusted dose can be safely used also for long term treatment regarding to cancer risk. Further studies are necessary to estimate cancer risk for increased chronic stress exposure.

The Caspian region and specifically the Apsheron peninsula of Azerbaijan is known to be polluted with a variety of environmental contaminants, making risk assessment difficult. The wetlands of Sumgayit contain particularly complex mixtures of contaminants. Flow cytometry and the micronucleus assay were used to assess chromosomal damage in aquatic turtles and frogs inhabiting contaminated wetlands in Azerbaijan. By evaluating biomarkers that are indicative of somatic effects, elevated chromosomal damage was documented at several sites in Azerbaijan relative to reference sites. Sediment samples were analyzed for polycyclic aromatic hydrocarbons (PAHs), organochlorines (OCs), and mercury to evaluate contaminant associations with genetic damage. Sediment samples revealed heterogeneous patterns of PAH and mercury concentrations throughout Sumgayit. Significant positive correlations were documented between both PAH and mercury sediment concentrations and chromosomal damage. Population genetic methods were employed to study the effects of long-term chronic contaminant exposure in marsh frogs from Sumgayit. The Sumgayit region has reduced levels of genetic diversity, likely due to environmental degradation. One of the most contaminated sites in Sumgayit, WTP, appears to be a source of new mutations as a result of an increased mutation rate. Finally, the Sumgayit region seems to act as an ecological sink, with levels of gene flow into the region exceeding gene flow out of the region. This study provides not only exposure and biomarker data, but also an integrated method for assessing the cumulative population impacts of contaminant exposure by studying both population genetic and evolutionary effects. The results presented here will be used in conjunction with those of ongoing research involving both wildlife and humans to develop comprehensive ecological and human risk assessments.

When food is heated, a vast number of compounds are formed. Some of these are known to be toxic. Among these are furan, HMF, PhIP, IQ, and MeIQx, the subjects of this thesis. All these compounds are known or suspected carcinogens but the detailed mechanisms behind their carcinogenicity have not yet been fully examined. The aim of this thesis was to study genotoxic properties of these compounds using both in vitro and in vivo methods. Clastogenic effects of all five compounds were assessed with the flow cytometer-based micronucleus assay in vivo and for furan also with the micronucleus assay in vitro. DNA-damaging effects of HMF were studied using the comet assay. No induction of micronuclei was obtained after exposure to IQ, MeIQx or furan. Hence, it can be argued that non-genotoxic mechanisms are partly responsible for the carcinogenic properties of these compounds. PhIP, on the other hand, generated a clear response in the in vivo test. Comparing these result with previous results on acrylamide indicates that PhIP is much more potent. However, acrylamide probably poses a higher risk for humans as the intake is considerably higher. For HMF no effects were seen using the in vivo setup. To further investigate the influence of bioactivation of HMF by sulfotransferases (SULTs) the comet assay was performed in cell lines expressing different levels of SULT. However, no correlation between SULT-expression and DNA-damage was observed. Thus, the DNA-damaging effects found in our experimental setup is probably due to other factors than SULT mediated effects. Furthermore, in this thesis the effects of folic acid on chromosomal stability in healthy people were studied. A negative correlation was found between micronucleus frequency and folate status. The results gained within this thesis will hopefully contribute to the risk assessment of compounds present in our diet.