Considerando os efeitos da radiação gama sobre proteínas e a capacidade do sistema imune de reconhecer macromoléculas modificadas, decidimos avaliar alguns aspectos imunológicos de camundongos B10.PL frente a ovalbumina e bothropstoxina–1 (BTHX-1), nas formas nativa e irradiada. Para avaliar prováveis modificações estruturais nas moléculas das proteínas após o processo de irradiação (radiação gama de 60Co), foi realizada a eletroforese em gel de poliacrilamida 15% para a ovalbumina e para a BTHX-1, nas formas nativa e irradiada. A ovalbumina também foi submetida à cromatografia de exclusão molecular, enquanto a BTHX-1 foi submetida à espectrometria de massa. Os resultados destes ensaios mostraram que a radiação gama foi capaz de promover alterações nas moléculas de ovalbumina e BTHX-1. A fim de avaliar a toxicidade da BTHX-1 irradiada em relação à nativa realizou-se um ensaio de citotoxicidade celular em células CHO. O resultado mostrou que a toxina na sua forma irradiada apresentou, aproximadamente, cinco vezes menos toxicidade do que a toxina na sua forma nativa. Com relação aos aspectos imunológicos, foram realizados ensaios de produção e identificação de anticorpos, nos quais, os animais foram imunizados com ovalbumina e BTHX-1, nas formas nativa ou irradiada. Observou-se que as proteínas nativas induziram, preferencialmente, uma resposta do tipo Th2, enquanto que as proteínas irradiadas induziram uma resposta do tipo Th1. Realizou-se um ensaio de proliferação celular para avaliar o comportamento de esplenócitos, retirados do baço de camundongos B10.PL, imunizados com ovalbumina e BTHX-1, nativas ou irradiadas, cultivados em presença de ambas as formas das proteínas. Em relação à ovalbumina, os resultados mostraram que tanto as células dos animais imunizados com a ovalbumina nativa como aquelas dos animais imunizados com a proteína na sua forma irradiada apresentaram crescimento semelhante. No caso da BTHX-1, os resultados mostraram que as células dos animais imunizados com a toxina irradiada foram capazes de reconhecer a forma nativa da toxina, pois apresentaram crescimento semelhante ao das células dos animais imunizados com a BTHX-1 nativa. / Considering the effects of gamma radiation on proteins and the capacity of the immune system to recognize modified macromolecules, we decided to evaluate some immunological aspects of B10.PL mice exposed to native or irradiated ovalbumin and bothropstoxin-1 (BthTx-1). In order to evaluate possible structural modifications of the molecules after being irradiated (60Co gamma rays), bothropstoxin-1 was analysed by electrophoresis, while ovalbumin was submitted to analytical size exclusion chromatography. The toxin was also analised by ESI-mass spectrometry. Our results indicate that radiation promoted modifications on both the molecules. Aiming to compare the toxicity of the native and irradiated forms of the toxin, an in vitro citotoxicity assay, using CHO cells, was performed. According to our results, the modified toxin was 5 folds less toxic than its native counterpart. Sera of animals immunized with the native and irradiated proteins were analyzed in order to evaluate levels of IgG, as well as to quantify specific isotypes. While the native proteins induced a predominant Th2 response, the irradiated molecules apparently promoted a switch towards a Th1 pattern. We also performed a cell proliferation assay with splenocites from mice immunized with either the native or the irradiated proteins, cultured in the presence of the antigens. Our results indicate that both the forms of the proteins induced a similar proliferative response. These data indicate a potential use of detoxified proteins as antigens for immunization.

O principal problema relativo aos acidentes com vazamentos de óleos combustíveis nos ambientes marinhos e costeiros é a contaminação pelos compostos benzeno, tolueno e xileno, (BTX), que possuem toxicidade elevada. O objetivo deste trabalho foi avaliar a contaminação da água do mar por BTX na região de Ubatuba, SP, entre 23º26’S e 23º46’S de latitude e 45º02’W e 45º11’W de longitude, que é uma área de transporte e produção de petróleo e estudar a eficiência da remoção destes compostos pela exposição à radiação ionizante proveniente de uma fonte de 60Co. A metodologia analítica utilizando o sistema de concentração “Purge and Trap” e o cromatógrafo CG-DIC, apresentou maior sensibilidade em água do mar do que o sistema de concentração “headspace” associado ao cromatógrafo CG-EM, com limite mínimo de detecção, LMD, de 0,50 &#956;g/L de benzeno, 0,70 &#956;g/L de tolueno e 1,54 &#956;g/L de xileno com uma variabilidade experimental (N=10) de cerca de 15%. Enquanto que o sistema CG-EM apresentou um LMD de BTX em água do mar de 9,30 mg/L para o benzeno, 8,50 mg/L para o tolueno e 9,80 mg/L para o xileno, com uma variabilidade experimental calculada nas mesmas condições de cerca de 10%. Foram realizadas quatro coletas de novembro de 2003 a julho de 2005 e a concentração de benzeno na água do mar variou de 1,0 &#956;g/L a 2,0 &#956;g/L, a de tolueno variou de <0,70 &#956;g/L a 3,24 &#956;g/L e para o xileno o valor máximo detectado foi de 2,92 &#956;g/L. No caso das amostras de água do mar contaminadas com padrões de BTX e expostas à radiação ionizante, a eficiência de remoção para o benzeno foi menor do que para os outros compostos considerando-se as mesmas concentrações, a taxa de remoção variou de 10% a 40% para dose absorvida de 20kGy e concentrações de 35,1 mg/L a 70,2 mg/L, respectivamente. O tolueno apresentou 20% a 60% de remoção para concentrações similares, mas com 15kGy de dose absorvida. Finalmente, o xileno foi removido com eficiência de 20% a 80% e 15 kGy de dose absorvida. / A major concern with leaking petroleum is the environmental contamination by the toxic and low water-soluble components such as benzene, toluene, and xylenes (BTX). These hydrocarbons have relatively high pollution potential because of their significant toxicity. The objective of this study was to evaluate the contamination of seawater by the main pollutants of the output and transport of petroleum, such as benzene, toluene, and xylene, and their removal by the exposure to the ionizing radiation. The studied region was Ubatuba region, SP, between 23º26’S and 23º46’S of latitude and 45º02’W and 45º11’W of longitude, area of carry and output of petroleum, and samples were collected from November, 2003 to July, 2005. For BTX in seawater analysis, the Purge and Trap concentrator with FIDGC detector showed significantly higher sensibility than Head Space concentrator with MSGC detector. The minimal detected limits (MDL) obtained at FIDGC were of 0.50 &#956;g/L for benzene, 0.70 &#956;g/L for toluene, and 1.54 &#956;g/L for xylene, and the obtained experimental variability was 15%. While the concentrator type Headspace system with MS detector showed higher MLD, about of 9.30 mg/L for benzene, 8.50 mg/L for toluene, and 9.80 mg/L for xylene, and 10% of experimental variability. In the studied area the benzene concentration varied from 1.0 &#956;g/L to 2.0 &#956;g/L, the concentration of toluene varied from < 0.70 &#956;g/L to 3.24 &#956;g/L and the maximum value of xylene observed was of 2.92 &#956;g/L. The seawater samples contaminated with BTX standard and exposed to ionizing radiation using a source of 60Co, presented a removal from 10% to 40% of benzene at 20 kGy absorbed doses and concentration of 35.1 mg/L and 70.2 mg/L, respectively; from 20% to 60% of toluene removal with 15 kGy absorbed dose and from 20% to 80% of xylene with 15 kGy absorbed dose in similar concentrations.

O tecido ósseo fornece sustentação e estrutura ao corpo, serve de alavanca para a função motora dos músculos esqueléticos, protege os órgãos internos, tem papel fundamental na fisiologia e está sujeito aos efeitos danosos da radiação ionizante. A estimativa para o Brasil, biênio 2016-2017, aponta a ocorrência de cerca de 600 mil casos novos de câncer e cerca de 8.000 solicitações de tecido ósseo para enxerto. Neste sentido a caracterização do tecido ósseo irradiado, através de técnicas de espectroscopia vibracional, pode ser uma importante ferramenta para compreender quais componentes são afetados e o quanto as diferentes doses de radiação ionizante alteram sua estrutura molecular. A técnica de espectroscopia ATR-FTIR (Attenuated Total Reflection Fourier Transform Infrared Spectroscopy), que permite análises qualitativas e semi-quantitativas, foi utilizada para caracterizar o tecido ósseo. Foram coletadas 110 amostras de diferentes fêmures bovinos e irradiadas com doses de 0,002 kGy; 0,004 kGy; 0,07 kGy; 1 kGy, 10 kGy, 15 kGy, 25 kGy, 35 kGy, 50 kGy e 60 kGy em fonte de 60Co. A espectroscopia ATR-FTIR demonstrou-se eficaz na caracterização do tecido e é possível afirmar que a radiação ionizante alterou a estrutura bioquímica do tecido ósseo, em sua matriz orgânica independente da dose aplicada e inorgânica a partir de 10 kGy. / Bone tissue provides support and structure to the body, function at the skeletal system providing muscle function, protects vital internal organs, plays a key role in physiology, and is subject to the damaging effects of radiation. The estimate for Brazil, biennium 2016-2017, indicates the occurrence of about 600 thousand new cases of cancer and about 8,000 requests of bone tissue for grafting. In this sense, the characterization of the irradiated bone tissue by means of vibrational spectroscopy techniques can be an important tool to understand which components are affected and how different doses of ionizing radiation alter their molecular structure. The ATR-FTIR (Attenuated Total Reflection) spectroscopy technique, which allows qualitative and semi-quantitative analyzes, was used to characterize bone tissue. A total of 110 samples of different bovine femurs were collected and irradiated at doses of 0.002 kGy; 0.004 kGy; 0.07 kGy; 1 kGy, 10 kGy, 15 kGy, 25 kGy, 35 kGy, 50 kGy and 60 kGy in 60Co source. ATR-FTIR spectroscopy proved to be effective in tissue characterization and it is possible to state that ionizing radiation altered the biochemical structure of the bone tissue in its organic matrix independent of the applied and inorganic dose from 10 kGy.

Rationale/Objective: Excess lung cancer risks associated with exposure to inhaled radon decay products among uranium miners has well been established. Although ingestion is also a potentially important route of exposure, the relationship between ingested radon decay products and gastrointestinal cancer risks are not well examined. The objective of this study is to determine the relationship between exposure to radon decay products and the incidence and mortality of gastrointestinal (esophagus, stomach, and colorectal) cancer among men employed as uranium miners in Ontario. Secondly, to determine whether the duration of exposure (dose rate), years since last exposure and age at first exposure modify these associations. Methods: A cohort of miners who had ever worked in an Ontario uranium mine between 1954 and 1996 was created using the Mining Master File and the National Dose Registry. Cumulative radon exposures measured in Working Level Months (WLM) were previously estimated for each miner. Cancer diagnoses (1964-2004) and cancer deaths (1954-2004) occurring in Ontario were determined by probabilistic record linkage with the Ontario Cancer Registry. To calculate person-years at risk, non-cancer deaths were also ascertained from the Ontario mortality file for the period between 1954 and 2004. Poisson regression methods for grouped data were used to estimate the relative risks (RR) and 95% Confidence Intervals (CI) by exposure level. Results/Conclusions: The final cohort consisted of 28,273 Ontario uranium miners. By the end of 2004, 34 miners had been diagnosed with esophageal cancer, 86 with stomach cancer, and 359 with colorectal cancer. There were 40 deaths due to esophageal cancer, 69 from stomach cancer, and 176 from colorectal cancer. When comparing the highest cumulative exposure category (>40 WLM) to the referent group (0 WLM), significant increases in both stomach (RRIncidence= 2.30, 95% CI;1.02-5.17 and RRMortality=2.90, 95% CI;1.11-7.63) and colorectal cancers (RRIncidence =1.56, 95% CI;1.07-2.27 and RRMortality =1.74, 95% CI;1.01-2.99) after adjusting for age at risk and period effects. However, no relationships were observed for esophageal cancer. Suggestive evidence of modifying effects of these associations by duration of employment (dose rate) and years since last exposure for colorectal cancer was also observed.

Rationale/Objective: Excess lung cancer risks associated with exposure to inhaled radon decay products among uranium miners has well been established. Although ingestion is also a potentially important route of exposure, the relationship between ingested radon decay products and gastrointestinal cancer risks are not well examined. The objective of this study is to determine the relationship between exposure to radon decay products and the incidence and mortality of gastrointestinal (esophagus, stomach, and colorectal) cancer among men employed as uranium miners in Ontario. Secondly, to determine whether the duration of exposure (dose rate), years since last exposure and age at first exposure modify these associations. Methods: A cohort of miners who had ever worked in an Ontario uranium mine between 1954 and 1996 was created using the Mining Master File and the National Dose Registry. Cumulative radon exposures measured in Working Level Months (WLM) were previously estimated for each miner. Cancer diagnoses (1964-2004) and cancer deaths (1954-2004) occurring in Ontario were determined by probabilistic record linkage with the Ontario Cancer Registry. To calculate person-years at risk, non-cancer deaths were also ascertained from the Ontario mortality file for the period between 1954 and 2004. Poisson regression methods for grouped data were used to estimate the relative risks (RR) and 95% Confidence Intervals (CI) by exposure level. Results/Conclusions: The final cohort consisted of 28,273 Ontario uranium miners. By the end of 2004, 34 miners had been diagnosed with esophageal cancer, 86 with stomach cancer, and 359 with colorectal cancer. There were 40 deaths due to esophageal cancer, 69 from stomach cancer, and 176 from colorectal cancer. When comparing the highest cumulative exposure category (>40 WLM) to the referent group (0 WLM), significant increases in both stomach (RRIncidence= 2.30, 95% CI;1.02-5.17 and RRMortality=2.90, 95% CI;1.11-7.63) and colorectal cancers (RRIncidence =1.56, 95% CI;1.07-2.27 and RRMortality =1.74, 95% CI;1.01-2.99) after adjusting for age at risk and period effects. However, no relationships were observed for esophageal cancer. Suggestive evidence of modifying effects of these associations by duration of employment (dose rate) and years since last exposure for colorectal cancer was also observed.

Τα αποτελέσματα ποικίλων δόσεων ακτινών Χ στην κυτταρική απόπτωση, τον πολλαπλασιασμό, την έκφραση του υποδοχέα του επιδερμικού αυξητικού παράγοντα (EGFR) και των μεταλλοπρωτεϊνασών-2 (MMP-2), μελετήθηκαν σε δύο κυτταρικές σειρές ανθρώπινου γλοιοβλαστώματος. Μέθοδος: Οι κυτταρικές σειρές LN18 και M059K ακτινοβολήθηκαν σε θερμοκρασία δωματίου με δόσεις κυμαινόμενες από 0,5 έως 15 Gy με τη χρήση πηγής 6 MV. Η απόπτωση μελετήθηκε με τη μέθοδο annexin V, ο πολλαπλασιασμός με τη μέθοδο MTT (methyl tetrazolium) και η έκκριση των MMP-2 με ζυμογράφημα. H καταγραφή των επιπέδων του φωσφοριωμένου EGFR έγινε με ELISA. Αποτελέσματα: Ο κυτταρικός πολλαπλασιασμός ανεστάλη με δόσο-εξαρτώμενο τρόπο ενώ η απόπτωση αυξήθηκε σημαντικά μετά την ακτινοβολία. Σε δόσεις μικρότερες των 2 Gy δεν καταγράφηκε καμία μεταβολή στην απόπτωση και τον κυτταρικό πολλαπλασιασμό. Τα επίπεδα των MMP-2 αυξήθηκαν 48 ώρες μετά την ακτινοβόληση με δόσο-εξαρτώμενο τρόπο. Αντιθέτως, η έκφραση του EGFR αυξήθηκε σημαντικά 15 λεπτά μετά την ακτινοβόληση και κατά δόσο-εξαρτώμενο τρόπο. Συμπέρασμα: Η ιοντίζουσα ακτινοβολία επάγει την έκφραση του EGFR και αυξάνει την έκκριση των MMP-2 γεγονός που αιτιολογεί την διηθητική και κακοήθη συμπεριφορά των γλοιωμάτων καθώς και την ανταπόκριση τους στην ιοντίζουσα ακτινοβολία. / The effect of different doses of X(-)rays on apoptosis, proliferation, epidermal growth factor receptor (EGFR) and matrix metalloproteinase (MMP-2) expression was investigated in a human glioblastoma cell line. Materials and Methods: The cell line LN18 was irradiated at room temperature with doses ranging from 0.5 to 15 Gy using 6 MV X(-)rays. Apoptosis was assessed using the annexin V binding assay, proliferation by the methyl tetrazolium (MTT) assay and MMP-2 secretion with zymography. The levels of phosphorylated (pEGFR) were estimated using a commercially available ELISA kit. Results: Cell proliferation decreased in a dose-dependent manner, while apoptosis was increased after radiation. Doses below 2 Gy did not affect proliferation or apoptosis. MMP-2 levels were increased 48 h after radiation in a dose-dependent manner. In contrast, EGFR signaling was significantly activated 15 min after radiation in a dose-dependent manner. Conclusion: Ionizing radiation activates EGFR signalling and enhances MMP-2 secretion, suggesting that the molecular pathways involved may contribute to the invasiveness and malignant behaviour of glioma cells and help to explain the response of gliomas to ionizing radiation.

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Thesis (Ph.D.)--Rochester Institute of Technology, 2008. / Typescript. Includes bibliographical references (leaves 151-155).

Thesis (M. Sc.)--Carleton University, 2001. / Includes bibliographical references (p. 79-84). Also available in electronic format on the Internet.