Дисертації з теми "Human PCOS"
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Weidemann, Annchen. "The role of fructose restriction in addition to dietary modifications for weight loss and lifestyle improvement, on fertility outcome and other markers of metabolic syndrome (MS), in obese women with polycystic ovarian syndrome (PCOS)." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71878.
Повний текст джерелаENGLISH ABSTRACT: The role of fructose restriction in addition to dietary modifications for weight loss and lifestyle improvement, on fertility outcome and other markers of metabolic syndrome, in obese women with polycystic ovarian syndrome (PCOS) Introduction: At the time at which the current study was undertaken no data, as yet, existed on whether restriction of fructose, while treating obese patients with PCOS for weight loss, improves the clinical symptoms and metabolic/anthropometric profile so as to promote fertility. Objectives: To evaluate the baseline intake of fructose, as well as the effect of restricting fructose intake from fruit and soft beverages to less than 20 g daily, as well as to provide guidelines for weight loss on anthropometric measurements, for improving subjective clinical symptoms, and for promoting fertility outcome in obese patients with PCOS, who seek to become fertile. Methods: The study was conducted in the Tygerberg Hospital Infertility Clinic, as an experimental cohort. Patients with a body mass index (BMI) higher than 27, seeking fertility after diagnosis with PCOS, were referred for dietary consultation, and followed up 3 monthly over 1 year. At each visit anthropometric measurements and a detailed dietary history were taken and a questionnaire for clinical symptoms was completed. Results: Baselinely, 86 patients were included in the study. Averages for weight and BMI were 99.8 ± 24.3 kg and 39.2 ± 8.7kg/m2, respectively. Average baseline daily fructose intake was 167 ± 116.8g. At baseline, significant relationships were shown between fructose intake and burning feet (ρ=0.02) and frequent waking (ρ=0.02), with a trend towards nightly eating (ρ=0.07). The dropout rate after visit 1 was 50%, with a further dropout of 41% after visit 2. After 3 visits (n=18), fructose intake significantly reduced (ρ=0.018), with the significant relationships with clinical symptoms having disappeared by visit 2. After 3 visits (n=18), both weight and BMI decreased significantly (ρ=0.017) and (ρ=0.019), respectively. Fructose was tested as a covariate to BMI, with high significance (ρ=0.006) in said population group. Conclusion: Dietary intervention to reduce fructose intake proved significant for weight loss and BMI after 3 visits. Reduced fructose intake was associated with reduced clinical symptoms. With fructose being a significant covariate to BMI, it can be concluded that fructose overconsumption could possibly contribute to both clinical symptoms and elevated BMI in said study population.
AFRIKAANSE OPSOMMING: Die rol wat die beperking van fruktose speel bykomend tot dieetaanpassings en lewenstylverbetering vir gewigsverlies by oorgewig vroue met polisistiese ovariële sindroom (PCOS) in die uitkoms van fertiliteit en ander merkers van metaboliese sindroom. Inleiding: Met die aanvang van hierdie studie was daar is geen data beskikbaar oor die invloed van die beperking van fruktose in die dieet van oorgewig pasiënte met PCOS wat vir gewigsverlies behandel word nie. Dit was ook nie bekend of laasgenoemde pasiënte se kliniese simptome en metaboliese/antropometriese profiel sou verbeter met die beperking van fruktose sodat fertiliteit by hierdie pasiënte terselfdertyd ook bevorder word nie. Doelwitte: Die evaluering van die aanvanklike inname van fruktose, sowel as die beperking van fruktose afkomstig van eetbare vrugte en versoete drankies en sap tot ’n inname van minder as 20 g daagliks, tesame met riglyne vir gewigsverlies. Die uitkoms hiervan is bepaal deur antropometriese metings, die verbetering in subjektiewe kliniese simptome en die fertiliteituitkoms by oorgewig pasiënte wat hulp met fertiliteit verlang. Metodes: Die studie het as ’n eksperimentele kohort by die Infertiliteitskliniek by Tygerberg Hospitaal plaasgevind. Pasiënte wat na diagnose met PCOS fertiliteitsbehandeling verlang het en ’n BMI hoër as 27 gehad het , is vir dieetbehandeling verwys en driemaandeliks oor ’n tydperk van een jaar opgevolg. Tydens elke besoek is antropometriese metings en ’n omvattende dieetgeskiedenis geneem en ’n vraelys oor kliniese simptome ingevul. Resultate: Aanvanklik is 86 pasiënte by die studie ingesluit. Gemiddeldes vir gewig en BMI was 99.8 ± 24.3 kg en 39.2 ± 8.7 kg/m2 respektiewelik. Gemiddelde aanvanklike daaglikse inname van fruktose was 167 ± 116.8 g. Oorspronklik het betekenisvolle verhoudings tussen fruktose en die volgende bestaan: brandvoete (ρ=0.02) en veelvuldige episodes van nagtelike wakkerheid (ρ=0.02), met ’n neiging na nagtelike etery (ρ=0.07). Die uitvalsyfer na een besoek was 50% met ’n verdere uitvalsyfer van 41% na die tweede besoek. Na drie besoeke (n=18) het sowel die gewig as die BMI betekenisvolle afname getoon (ρ= 0.017) en (ρ=0.019), respektiewelik. Fruktose is as ’n belangrike kovariant vir BMI (ρ= 0.006) vir hierdie populasiegroep geïdentifiseer. Gevolgtrekking: Dieetintervensie vir die vermindering van die inname van fruktose was beduidend vir gewigsverlies en afname in BMI na drie besoeke. Verminderde fruktose-inname het gelei tot die vermindering van kliniese simptome. Met fruktose as beduidende kovariant vir BMI kan die gevolgtrekking gemaak word dat die oor-inname van fruktose by hierdie studiepopulasie waarskynlik tot sowel kliniese simptome as BMI bygedra het.
Braga, Ana Maria Cheble Bahia. "Dioxinas, furanos e PCBs em leite humano no Brasil." [s.n.], 2003. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310590.
Повний текст джерелаTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-05T19:02:29Z (GMT). No. of bitstreams: 1 Braga_AnaMariaChebleBahia_D.pdf: 1900359 bytes, checksum: 79e7312e2649cd6e41634906f1302f41 (MD5) Previous issue date: 2003
Resumo: O presente estudo é pioneiro no Brasil e ganha relevância tendo em vista as várias possíveis fontes antropogênicas de PCBs, PCDDs e PCDFs ainda não mapeadas, da ocorrência de acidentes com exposição a produtos clorados em populações brasileiras e da presença, de detecção recente, na ração animal aqui produzida e exportada para a Europa. O objetivo principal foi avaliar a exposição da população geral, utilizando-se o leite humano como bioindicador, com vistas a subsidiar ações de prevenção e controle de emissões destes poluentes para o meio ambiente, como forma efetiva de minimizar a exposição humana. Sendo também parte da terceira rodada dos estudos de exposição organizada pela OMS, a metodologia utilizada seguiu seu protocolo já validado. Em cada uma das 10 áreas amostradas, nas diferentes regiões do país, foram coletadas 10 amostras individuais, conformando uma amostra composta que foi enviada para análise no laboratório de referência da OMS na Alemanha. As amostras de leite humano foram coletadas, em sua maioria, em bancos de leite humano integrantes da Rede Nacional de Bancos de Leite Humano, usando critérios pré-definidos para a seleção das mães doadoras. Ao nível mundial, dos 24 países participantes do estudo, as concentrações encontradas no Brasil foram as mais baixas. Propõe-se um programa de monitoramento destas substâncias e outros Poluentes Orgânicos Persistentes em leite humano e em amostras ambientais como ação preventiva e de controle, incrementando o conhecimento a respeito da ocorrência destes compostos no Brasil, para subsidiar o gerenciamento das substâncias químicas e os acordos internacionais como a Convenção de Estocolmo
Abstract: The presented research is pioneer in brazil and its relevance is due to the various unmapped possible anthropogenic sources of PCBs, PCDDs and PCDFs, to the occurrence of accidents with chlorinated products exposing brazilian populations and the recent episode related to the presence of such contaminants in feedstuff exported to europe. The main objective of this study was to evaluate the exposure of the general population considering human milk as good indicator. Moreover, the study may subsidize future preventing actions and emission control of these pollutants to the environment as an effective manner to minimize human exposure. being also part of the third round of exposure studies organized by WHO, the used methodology followed the validated WHO¿s protocol, as well. In each of the ten sampled areas from different brazilian regions, it was collected ten individual samples to form one pooled sample which was sent to the WHO¿s reference laboratory in Germany. Human milk samples were mostly collected from human milk banks which are part of the National Human Milk Bank Network. Donors were selected considering the prior defined eligibility criteria. On worldwide level, the concentrations found in brazil were the lowest among the 24 participant countries. A monitoring program of these substances e others Persistent Organic Pollutants in human milk and environmental samples is proposed as prevention and control actions. Besides extending the knowledge about the occurrence of these compounds in Brazil, the study may subsidize international programs such as the Stockholm Convention and improve the management of chemical substances
Doutorado
Saude Ambiental
Doutor em Saude Coletiva
Juan, Ching-yi Amy. "Studies on the intake and behaviour of PCBs in humans." Thesis, Lancaster University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274223.
Повний текст джерелаPerumal, Kuppusamy Senthilkumar. "Telomerase and telomere dysregulation in Polychlorinated Biphenyl (PCB) exposed human skin keratinocytes." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/2957.
Повний текст джерелаKhabazbashi, Sara. "Analytical Standard Free Semi-Quantification of OH-PCBs in human blood serum samples." Thesis, Karlstads universitet, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-84442.
Повний текст джерелаGrimm, Fabian Alexander. "Toxicological and therapeutic implications of interactions between polychlorinated biphenyl sulfates and human transthyretin." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/4635.
Повний текст джерелаBoulay, Hillary Michelle. "The effect of cisplatin on the role of proprotein convertases (PCs) in human ovarian cancer cells." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27319.
Повний текст джерелаHazrati, Sadegh. "The signiflcance of indoor air as a source of human exposure to polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs)." Thesis, University of Birmingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.633125.
Повний текст джерелаMagan, Christopher L. "Human health risk characterization for dietary exposure to polychlorinated biphenyls (PCBs) in fish from the Columbia Basin Irrigation Project a probabilistic approach /." Pullman, Wash. : Washington State University, 2009. http://www.dissertations.wsu.edu/Thesis/Spring2009/c_magan_041709.pdf.
Повний текст джерелаTitle from PDF title page (viewed on May 28, 2009). "School of Earth and Environmental Sciences." Includes bibliographical references (p. 56-63).
Rodriguez, Eric Alberto. "Hydroxylated and sulfated metabolites of lower chlorinated PCBs bind with high affinity to human serum albumin and exhibit selective toxicity to neuronal cells." Diss., University of Iowa, 2016. https://ir.uiowa.edu/etd/3175.
Повний текст джерелаSandau, Courtney Douglas. "Analytical chemistry of hydroxylated metabolites of PCBs and other halogenated phenolic compounds in blood and their relationship to thyroid hormone and retinol homeostasis in humans and polar bears." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ57637.pdf.
Повний текст джерелаSandau, Courtney Douglas Carleton University Dissertation Chemistry. "Analytical chemistry of hydroxylated metabolites of PCBs and other halogenated phenolic compounds in blood and their relationship to thyroid hormone and retinol homeostasis in humans and polar bears." Ottawa, 2000.
Знайти повний текст джерелаGeng, Dawei. "Gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry methods for the determination of environmental contaminants." Doctoral thesis, Örebro universitet, Institutionen för naturvetenskap och teknik, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-51727.
Повний текст джерелаAugulyte, Lijana. "Use and Development of Diffusive Samplers to Analyse the Fate of Polycyclic Aromatic Compounds, Polychlorinated Biphenyls and Pharmaceuticals in Wastewater Treatment Processes." Doctoral thesis, Umeå : Department of Chemistry, Umeå University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1912.
Повний текст джерелаAlhaddad, Abdolrauf Gawad. "Balanced antennas for mobile handset applications : simulation and measurement of balanced antennas for mobile handsets, investigating specific absorption rate when operated near the human body, and a coplanar waveguide alternative to the balanced feed." Thesis, University of Bradford, 2012. http://hdl.handle.net/10454/5512.
Повний текст джерелаAlhaddad, A. G. "Balanced antennas for mobile handset applications. Simulation and Measurement of Balanced Antennas for Mobile Handsets, investigating Specific Absorption Rate when operated near the human body, and a Coplanar Waveguide alternative to the Balanced Feed." Thesis, University of Bradford, 2012. http://hdl.handle.net/10454/5512.
Повний текст джерелаUK Engineering and Physical Sciences Research Council (EPSRC)
Cachada, Anabela Ferreira de Oliveira. "Organic contaminants in urban soils: major inputs and potential risks." Doctoral thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/14130.
Повний текст джерелаUrban soil quality may be severely affected by hydrophobic organic contaminants (HOCs), impairing environmental quality and human health. A comprehensive study was conducted in two contrasting Portuguese urban areas (Lisbon and Viseu) in order to assess the levels and potential risks of these contaminants, to identify sources and study their behaviour in soils. The concentrations of HOCs were related to the size of the city, with much higher contamination levels observed in Lisbon urban area. Source apportionment was performed by studying the HOCs profiles, their relationship with potentially toxic elements and general characteristics of soil using multivariate statistical methods. Lisbon seems to be affected by nearby sources (traffic, industry and incineration processes) whereas in Viseu the atmospheric transport may be playing an important role. In a first tier of risk assessment (RA) it was possible to identify polycyclic aromatic hydrocarbons (PAHs) in Lisbon soils as a potential hazard. The levels of PAHs in street dusts were further studied and allowed to clarify that traffic, tire and pavement debris can be an important source of PAHs to urban soils. Street dusts were also identified as being a potential concern regarding human and environmental health, especially if reaching the nearby aquatic bodies. Geostatistical tools were also used and their usefulness in a RA analysis and urban planning was discussed. In order to obtain a more realistic assessment of risks of HOCs to environment and human health it is important to evaluate their available fraction, which is also the most accessible for organisms. Therefore, a review of the processes involved on the availability of PAHs was performed and the outputs produced by the different chemical methods were evaluated. The suitability of chemical methods to predict bioavailability of PAHs in dissimilar naturally contaminated soils has not been demonstrated, being especially difficult for high molecular weight compounds. No clear relationship between chemical and biological availability was found in this work. Yet, in spite of the very high total concentrations found in some Lisbon soils, both the water soluble fraction and the body residues resulting from bioaccumulation assays were generally very low, which may be due to aging phenomena. It was observed that the percentage of soluble fraction of PAHs in soils was found to be different among compounds and mostly regulated by soil properties. Regarding bioaccumulation assays, although no significant relationship was found between soil properties and bioavailability, it was verified that biota-to-soil bioaccumulation factors were sample dependent rather than compound dependent. In conclusion, once the compounds of potential concern are targeted, then performing a chemical screening as a first tier can be a simple and effective approach to start a RA. However, reliable data is still required to improve the existing models for risk characterization.
A qualidade dos solos urbanos pode ser afetada por contaminantes orgânicos hidrofóbicos (HOCs), prejudicando a saúde ambiental e humana. Este trabalho consistiu em estudar duas áreas urbanas contrastantes (Lisboa e Viseu), com o objetivo de avaliar os níveis de HOCs nos solos e os seus potenciais riscos para a saúde humana e para o ambiente. Pretendia-se ainda identificar as fontes e estudar o comportamento destes contaminantes no solo. Foi possível relacionar as concentrações de HOCs com o tamanho da cidade, sendo os níveis de contaminação muito mais elevados em Lisboa. A identificação das fontes destes contaminantes foi feita através do estudo dos respetivos perfis e da relação com elementos potencialmente tóxicos, utilizando métodos estatísticos multivariados. Lisboa parece ser afetada por fontes próximas (tráfego, indústria e incineração) enquanto em Viseu o transporte atmosférico aparenta ter um papel mais importante. Num primeiro nível da avaliação de risco (RA), foi possível identificar os hidrocarbonetos aromáticos policíclicos (PAHs) nos solos de Lisboa como um perigo potencial. Os níveis de PAHs em poeiras das ruas de Lisboa foram também estudados e permitiram clarificar que o tráfego e os detritos de pneus e de pavimento podem também ser uma importante fonte destes compostos. Utilizaram-se e discutiram-se ferramentas de geoestatística assim como a respetiva utilidade em RA e em planeamento urbano. De modo a obter uma avaliação mais realista dos riscos de HOCs é importante avaliar a fração disponível, que é também a mais acessível para os organismos. Deste modo, foi feita uma avaliação dos processos envolvidos na disponibilidade de PAHs e também dos resultados obtidos pelos diferentes métodos químicos. A adequação dos métodos químicos para prever a biodisponibilidade de PAHs em solos naturalmente contaminados ainda não foi demonstrada, sendo especialmente difícil para os compostos de elevado peso molecular. No presente trabalho também não foi possível estabelecer uma relação significativa entre a disponibilidade química e a biodisponibilidade. No entanto, apesar das elevadas concentrações totais encontradas em alguns solos de Lisboa, tanto a fração solúvel em água como os resíduos acumulados nos ensaios de bioacumulação foram, em geral, muito baixos, o que estará relacionado com os fenómenos de envelhecimento destes contaminantes nos solos. Observou-se que a fração solúvel de PAHs depende do composto em causa e é regulada pelas propriedades do solo. Apesar de não se terem observado correlações entre as propriedades do solo e a biodisponibilidade, observou-se que os fatores de bioacumulação dependem mais da amostra do que do composto. Em conclusão: após a identificação dos contaminantes de interesse uma avaliação química baseada nos teores totais pode ser uma abordagem eficaz no primeiro nível da RA, mas no entanto é necessário melhorar os modelos existentes para a caracterização do risco.
Lutz, Elizabeth Anne. "Effects of Modified Cyclosporine A on Posterior Capsule Opacification Formation and Corneal Endothelial Cell Viability in an Ex Vivo Model." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1371477702.
Повний текст джерелаTuck, Astrud Rebecca Rose. "Investigation into the expression and localisation of c-kit and the regulation of kit ligand gene expression in the adult human ovary." Thesis, 2013. http://hdl.handle.net/2440/80602.
Повний текст джерелаThesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2013
McIlvenna, Luke. "Polycystic Ovary Syndrome and Insulin Resistance: Dysregulation of Transforming Growth Factor Beta Signalling and the Effects of Exercise Training." Thesis, 2021. https://vuir.vu.edu.au/42295/.
Повний текст джерела"Dioxinas, furanos e PCBs em leite humano no Brasil." Tese, Biblioteca Digital da Unicamp, 2003. http://libdigi.unicamp.br/document/?code=vtls000376714.
Повний текст джерелаKennedy, Katherine Margaret. "Molecular methods for evaluating the human microbiome." Thesis, 2014. http://hdl.handle.net/10012/8230.
Повний текст джерелаWeiß, N., A. Stegemann, Marwa A. T. A. Elsayed, Karin U. Schallreuter, T. A. Luger, K. Loser, D. Metze, C. Weishaupt, and M. Böhm. "Inhibition of the prohormone convertase subtilisin-kexin isoenzyme-1 induces apoptosis in human melanoma cells." 2014. http://hdl.handle.net/10454/7065.
Повний текст джерелаProhormone convertases (PCs) are endoproteases that process many substrates in addition to hormone precursors. Although overexpression of PCs is linked to carcinogenesis in some solid tumors, the role of subtilisin-kexin isoenzyme-1 (SKI-1) in this context is unknown. We show that SKI-1 is constitutively expressed in human pigment cells with higher SKI activity in seven out of eight melanoma cell lines compared with normal melanocytes. SKI-1 immunoreactivity is also detectable in tumor cells of melanoma metastases. Moreover, tissue samples of the latter display higher SKI-1 mRNA levels and activity than normal skin. From various stimuli tested, 12-O-tetradecanoylphorbol-13-acetate and tunicamycin affected SKI-1 expression. Importantly, SKI-1 inhibition by the cell-permeable enzyme inhibitor decanoyl-RRLL-chloromethylketone (dec-RRLL-CMK) not only suppressed proliferation and metabolic activity of melanoma cells in vitro but also reduced tumor growth of melanoma cells injected intracutaneously into immunodeficient mice. Mechanistic studies revealed that dec-RRLL-CMK induces classical apoptosis of melanoma cells in vitro and affects expression of several SKI-1 target genes including activating transcription factor 6 (ATF6). However, ATF6 gene silencing does not result in apoptosis of melanoma cells, suggesting that dec-RRLL-CMK induces cell death in an ATF6-independent manner. Our findings encourage further studies on SKI-1 as a potential target for melanoma therapy.
Coombs, Andrea Pauline. "Marine mammals and human health in the Eastern Bering Sea : using an ecosystem-based food web model to track PCBs." Thesis, 2004. http://hdl.handle.net/2429/15476.
Повний текст джерелаNyberg, Elisabeth. "Improved Assessment in Environmental Monitoring of POPs : Using monitoring data from the aquatic ecosystem and human milk." Doctoral thesis, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-134769.
Повний текст джерелаYa-Hsin, Chou, та 周雅炘. "Effects of polychlorinated biphenyls (PCBs) on the induction of cell toxicity, DNA damage and altered gene expression by 17β-estradiol in human breast carcinoma cell lines". Thesis, 2005. http://ndltd.ncl.edu.tw/handle/10203183548422254988.
Повний текст джерела國立中興大學
環境工程學系
93
The objective of this research is to investigate the effects of polychlorinated biphenyls (PCBs) (i.e. PCB126 and PCB153), on the induction of imbalances in gene expression, formation of reactive oxygen species (ROS), oxidative DNA damage and cell toxicity by 17β-estradiol (E2) in human breast cancer cell lines, including estrogen receptor α (ERα)(+)/MCF-7 and ERα(-)/MDA-MB-231 cells. Results indicated that E2, PCB126, and PCB153 induced concentration- and time-dependent increases in cytotoxic response in both MCF-7 and MDA-MB-231 cells. The extent of cytotoxic response in human breast cancer cells was greater for PCB153 than for PCB126 in these two cell lines. The data also showed that at non-cytotoxic concentrations, E2 induces concentrations-dependent increases in intracellular levels of ROS in MDA-MB-231 cells. Pretreatment with PCB126 did not alter the induction of ROS by E2 in MDA-MB-231 cells. α-Naphthoflavone (a CYP1A1/1B1 inhibitor) completely blocked the E2-induced increases in the amount of intracellular ROS in MDA-MB-231 cells pretreatment of PCB126 (20 μM) and PCB mixture [PCB126 (20μM)+PCB153 (1μM)]. In contrast, induction of ROS formation by E2 in MDA-MB-231 cells was inhibited with pretreatment of PCB153. Additionally, E2 did not induce increases in intracellular ROS in MCF-7 cells. However, when cells were pretreated with PCB153, increases in intracellular ROS was detected in E2-treated MCF-7 cells. Further investigation indicated that E2 induces decreases in intracellular NAD(P)H and NAD+ by PARP-1 [poly(ADP-ribose) polymerase-1] activation through formation of DNA strand breaks in MDA-MB-231 cells at physiologically relevant concentration (1-10 nM). Pretreatment with PCB126 did not alter the E2-induced PARP-1 activation in MDA-MB-231 cells. In contrast, pretreatment of PCB153 inhibits the E2-induced PARP-1 activation in MDA-MB-231 cells. When MCF-7 cells were exposed to E2 (0.1 nM-10 nM) alone, we did not observe decreases in intracellular NAD(P)H, whereas pretreatment of cells with PCB153 significantly reduces intracellular NAD(P)H in MCF-7 cells exposed to E2. Results from semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay indicated that E2 induced increases in the expression of CYP1A1, CYP1B1, and hOGG1, XRCC1 genes in MDA-MB-231 cells. Pretreatment of PCB153 inhibits the E2-induced CYP1A1, CYP1B1, hOGG1 and XRCC1 gene expression in MDA-MB-231 cells. PCB153 and E2 alone induced increases in the expression of CYP1A1 and CYP1B1 in MCF-7 cells. Pretreatment of PCB153 increases the E2-induced CYP1A1 gene expression in MCF-7 cells. PCB153 alone can inhibits the hOGG1 and XRCC1 gene expression in MCF-7 cels. This result suggests that exposure to PCB153 alters gene expression in the disposition of estrogen and DNA repair. In conclusions, this evidence suggests that both planar and non-planar PCB congeners modulate different profile of estrogen-induced formation of ROS, DNA lesions, and cell toxicity in human breast cancer cells. The data also suggests that the status of estrogen receptor a may play a role in modulating the E2-mediated induction of oxidative DNA lesions and cell toxicity in human breast cancer cells.
Huang, Ching-Lung, and 黃景隆. "Effects of metabolic activation and altered gene expression on the induction of oxidative stress, DNA damage, and cell toxicity in human breast cancer cells by polychlorinated biphenyls (PCBs)." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/34040164716643403534.
Повний текст джерела國立中興大學
環境工程學系
93
The objective of this research is to examine the effects of metabolic activation and altered gene expression on the induction of oxidative stress, DNA damage, and cell toxicity by polychlorinated biphenyls (PCBs), including PCB52 and PCB77, in human ERα(++)/MCF-7, ERα(+)/T47D and ERα(-)/MDA-MB-231 breast cancer cells. Results indicated that both PCB52 and PCB77 induced concentration- and time-dependent increases in cytotoxic response in MCF-7, T47D, and MDA-MB-231 cells. The extent of cytotoxic response induced by these two PCB congeners in human breast cancer cells was greater for PCB52 than for PCB77. Additionally, the reduction in the number of viable cells exposed to PCBs was primarily mediated by apoptosis. Further, α-naphthoflavone, resveratrol, and metyrapone blocked the PCB52-induced cell toxicity in T47D and MDA-MB-231 cells, but not in MCF-7 cells. The data also showed that PCB52 and PCB77 induced significant increases in intracellular levels of reactive oxygen species (ROS) in MCF-7, T47D, and MDA-MB-231 cells, particularly in MDA-MB-231 cells. In addition, when cells were exposed to PCBs at non-cytotoxic concentration, we observed that PCB52 (1 mM) and PCB77 (10 mM) alone or mixture did not induce decreases in intracellular NAD(P)H in MCF-7 cells. In contrast, both PCB52 and PCB77 induced decreases in intracellular NAD(P)H and NAD+ through formation of DNA strand breaks and poly(ADP-ribose)polymerase-1 activation in T47D and MDA-MB-231 cells. Antagonism was detected in T47D and MDA-MB-231 cells exposed to PCB52/PCB77 mixture. Further, results from semi-quantitative reverse-transcription polymerase chain reaction (semi-quantitative RT-PCR) analyses indicated that exposure to PCB77 (10 mM) induced increases in the expression of CYP1A1, hAPE, and XRCC1 whereas PCB52 (1 mM) alone induced increases in the expression of hOGG1, hAPE, and XRCC1. Similar observation was also detected in MCF-7 cells exposed to PCB52/PCB77 mixture. On the other hand, both PCB52 (10 mM) and PCB77 (10 mM) induced increases in the expression of CYP1A1 and XRCC1 genes whereas PCB52/PCB77 mixture induced increases in the expression of CYP1A1 in MDA-MB-231 cells. Overall, this evidence indicates that both PCB52 and PCB77 may induce ROS formation and imbalances in the expression of genes responsible for the DNA repair process and apoptosis in MCF-7 cells. In contrast, PCB52 and PCB77 are likely to mediate the induction of ROS formation, DNA strand breaks, and cell toxicity through futile cycling and/or redox cycling in MDA-MB-231 cells. The data also suggests that the status of estrogen receptor a may play a role in modulating the PCB-induced DNA damage and cytotoxic response in human breast cancer cells.