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Owing to their unique physical, chemical, and mechanical properties, nanoparticles (NPs) have been used, or are being evaluated for use, in many fields (e.g., personal care and cosmetics, pharmaceutical, energy, electronics, food and textile). However, concerns regarding the environmental and biological implications of NPs are raised alongside the booming nanotechnology industry. Numerous studies on the biological effect of NPs have been done in the last decade, and many mechanisms have been proposed. In brief, mechanisms underlying the adverse biological effect caused by NPs can be summarized as: (i) indirect adverse effect induced by reactive oxygen species (ROS) generated by NPs, (ii) indirect adverse effect induced by released toxic ions, and (iii) adverse effect induced by direct interactions of NPs with biological systems. Up to now, most efforts have been focused on the first two mechanisms. In contrast, adverse biological effects induced by direct nano-bio interactions are the least researched. This is largely because of the complexity and lack of suitable techniques for characterizing the nano-bio interface. This dissertation aims at advancing our understanding of the nano-bio interactions leading to the adverse biological effect of NPs. Specifically, it is comprised of three parts. Firstly, because the aggregation of NPs alters particle size and other physicochemical properties of NPs, the property of NPs reaching and interacting with biological cells is very likely different from that of what we feed initially. Consequently, as the first step and an essential prerequisite for understanding the biological effect of NPs, NP aggregation is investigated and models are developed for predicting the stability and the extent of aggregation of NPs. Secondly, interactions between NPs and cell membrane are studied with paramecium as the model cell. Due to the lack of cell wall, the susceptible cell membrane of paramecium is directly exposed to NPs in the medium. The extent and strength of direct nano-cell membrane interaction is evaluated and quantified by calculating the interfacial force/interaction between NPs and cell membrane. A correlation is further established between the nano-cell membrane interaction and the lethal acute toxicity of NPs. We find NPs that have strong association or interaction with the cell membrane tend to induce strong lethal effects. Lastly, we demonstrate systematic experimental approaches based on atomic force microscope (AFM), which allows us to characterize nano-bio interfaces on the single NP and single-molecular level, coupled with modeling approaches to probe the nano-DNA interaction. Using quantum dots (QDs) as a model NP, we have examined, with the novel application of AFM, the NP-to-DNA binding characteristics including binding mechanism, binding kinetics, binding isotherm, and binding specificity. We have further assessed the binding affinity of NPs for DNA by calculating their interaction energy on the basis of the DLVO models. The modeling results of binding affinity are validated by the NP-to-DNA binding images acquired by AFM. The investigation of the relationship between the binding affinity of twelve NPs for DNA with their inhibition effects on DNA replication suggests that strong nano-DNA interactions result in strong adverse genetic effects of NPs. In summary, this dissertation has furthered our understanding of direct nano-bio interactions and their role in the biological effect of NPs. Furthermore, the models developed in this dissertation lay the basis for building an “ultimate” predictive model of biological effects of NPs that takes into account multiple mechanisms and their interactions, which would save a lot of testing costs and time in evaluating the risk of NPs.

[pt] Com a implantação e disseminação de novos sistemas celulares,principalmente a partir dos anos 80, novas tecnologias foram desenvolvidas, o número de celulares cresceu de forma surpreendente, como conseqüência, o aumento de Estações Radio Base. É fato, também, que as pessoas, de modo geral, estão expostas às radiações emitidas pelas ERBs através de suas antenas. Como a população, a mais interessada na busca de respostas adequadas e convincentes, não tem qualquer controle sobre tais níveis, cabe as autoridades a preocupação maior em garantir que os níveis de exposição não sejam excedidos. A partir deste quadro preocupante a OMS estabeleceu em 1996 o International EMF Project para avaliar as evidências cientificas existentes sobre possíveis efeitos de campos eletromagnéticos à saúde,incluindo nestes os efeitos emitidos pelos próprios aparelhos celulares e por suas estações rádio-base. Este trabalho pretende contribuir no equacionamento desta questão, tão polemica e controversa. Iniciando com a evolução do número de celulares no Brasil, mostrando as funções básicas dos componentes de uma estrutura celular. No momento seguinte são mostrados alguns efeitos biológicos relacionados à radiação não-ionizante pesquisados na literatura. Tais efeitos, polêmicos e controversos, são amplamente discutidos por especialistas de diferentes linhas de pesquisa. O trabalho mostra, também, os resultados de uma campanha de medidas com as densidades de potência obtidas através de duas metodologias. Inclui, também, conceitos e características de percepção de risco e alguns resultados da pesquisa qualitativa de campo. Ao final são apresentadas as conclusões e sugestões para trabalhos futuros relacionados ao tema. / [en] With the implantation and spread of new cellular systems, mainly starting from the eighties, new technologies were developed, the number of cellular grew in a surprising way, as consequence, the Base Stations increased, too. The people, in general, are exposed to the radiations emitted by ERBs antennae. As the population doesn't have any control on such levels, people are always looking for appropriate and convincing answers. So, the authorities are concerned in guaranteeing that the exposition levels are not exceeded. Based on preoccupying issue, the World Health Organization (WHO) established in 1996 International EMF Project to verify the scientific evidence of possible health effects of Electromagnetic Field. This work intends to contribute in the set out of this controversial subject. At first, the cellular number evolution in Brazil is presented. In addition, the basic cellular structure components functions are described. The following topic presents some biological effects related to the non-ionizing radiation are presented according to the literature. Such controversial effects are discussed thoroughly by specialists of different research lines. This work also shows the power densities results obtained through two methodologies. Afterwards, concepts, risk perception characteristics and some results from a qualitative research are presented. At the end, the conclusions and suggestions for future works related to the same theme are shown.

At low doses, relevant to nuclear incidents and accidental releases of radioactivity, the detriment of radiation extends beyond direct effects. This thesis investigates genomic instability, a subclass of non-targeted effects where damage and lethality is transmitted vertically and expressed in the progeny of cells many generations after initial radiation exposure. Through a series of experiments using clonogenic assay of human and fish cell culture, studies described in this thesis describe lethal mutations, hyper radiosensitivity and increased radioresistance – processes involving repair mechanisms that dictate survival in cells exposed to low doses. Further study investigates the difference in the relative biological effect of alpha particle radiation compared to what is expected at high doses. Results demonstrate increased radioresistance in a human cell line while also revealing increased lethality in a fish cell line confirming the need for consideration of dose-dependence as well as variance in behaviors of different cell lines and species. It is hoped the conclusions of this thesis will inspire the creation of protocols with greater attention to the indirect consequences of exposure to radiation at doses relevant to nuclear incidents and accidents. / Thesis / Master of Science (MSc)