Mixed beams of ionizing radiation in our environment originate from space, the bedrock and our own houses. Radiotherapy patients treated with boron neutron capture therapy or with high energy photons are also exposed to mixed beams of gamma radiation and neutrons. Earlier investigations have reported additivity as well as synergism (a greater than additive response) when combining radiations of different linear energy transfer. However, the outcome seemed to be dependent on the experimental setup, especially the order of irradiation and the temperature at exposure. A unique facility allowing simultaneously exposure of cells to X-rays and 241Am alpha particles at 37 ºC was constructed and characterized at the Stockholm University (Paper I). To investigate the cytogenetic response to mixed beam irradiation (graded doses of alpha particles, X-rays or a mixture of both) several different cell types were utilized. AA8 Chinese Hamster Ovary cells were analyzed for clonogenic survival (Paper I), human peripheral blood lymphocytes were analyzed for micronuclei and chromosomal aberrations (Paper II and Paper III respectively) and VH10 normal human fibroblasts were scored for gamma-H2AX foci (Paper IV). For clonogenic survival, mixed beam results were additive, while a significant synergistic effect was observed for micronuclei and chromosomal aberrations. The micronuclei dose responses were linear, and a significant synergistic effect was present at all investigated doses. From the analysis of micronuclei distributions we speculated that the synergistic effect was due to an impaired repair of X-ray induced DNA damage, a conclusion that was supported by chromosomal aberration results. Gamma-H2AX foci dose responses were additive 1 h after exposure, but the kinetics indicated that the presence of low LET-induced damage engages the DNA repair machinery, leading to a delayed repair of the more complex DNA damage induced by alpha particles. These conclusions are not necessary contradictory since fast repair does not necessarily equal correct repair. Taken together, the observed synergistic effects indicate that the risks of stochastic effects from mixed beam exposure may be higher than expected from adding the individual dose components. / <p>At the time of the doctoral defence the following papers were unpublished and had a status as follows: Paper nr 3: Manuscript; Paper nr 4: Manuscript.</p> / DNA damage and repair in cells exposed to mixed beams of radiation

Hearing loss from noise exposure is one of the most common occupational injuries, and exposure to vibrations may increase the risk of noise-induced hearing loss. Earlier cross-sectional and longitudinal studies found an increased risk of noise-induced hearing loss among workers with vibration-induced white fingers (VWF) symptoms compared to workers without such symptoms. It has been suggested that vibrations to the hand stimulate the sympathetic nervous system and cause vasoconstriction in both the exposed hand and the ears and that this contributes to noise-induced hearing loss. The overall aim of this thesis was to examine how hand-arm vibrations (HAV) interact with noise in the development of noise-induced hearing loss. The experimental study in this thesis examined the effects of HAV and noise, both separately and combined, on the temporary threshold shift (TTS) in hearing in 22 healthy male and female subjects. The two longitudinal studies in this thesis were based on a cohort of 189 male workers at a heavy engineering workshop. The first cohort study examined the risk of noise-induced hearing loss from long-term exposure to HAV and noise. The second cohort study examined if workers with VWF had an increased risk of noise-induced hearing loss compared to workers without such symptoms. Finally, the questionnaire study in this thesis examined the occurrence of Raynaud’s phenomenon among 133 men and women with noise-induced hearing loss in relation to exposure to vibrations. In the experimental study, no differences in TTS in hearing were observed after combined exposure to HAV and noise compared to exposure to only noise. In the first cohort study, there was an increased risk of noise-induced hearing loss with increased exposure to HAV in a noisy environment. In the second cohort study, it was found that workers with VWF had an increased risk of noise-induced hearing loss compared to workers without VWF. In the questionnaire study, many men and women with noise-induced hearing loss had used hand-held vibrating machines suggesting that vibrations might contribute to noise-induced hearing loss. A high prevalence of Raynaud’s phenomenon was found among men. This thesis demonstrated that there was a long-term effect on noise-induced hearing loss from combined exposure to noise and HAV, but no short-term effect, and that having Raynaud’s phenomenon may also increase the risk of noise-induced hearing loss. / Många arbetare använder sig av handhållna vibrerande verktyg. Det utsätter dem för höga nivåer av både buller och vibrationer. Människor som utsätts för höga bullernivåer under lång tid kan skada sin hörsel. Risken för hörselnedsättning orsakad av buller kan eventuellt öka om personen samtidigt är utsatt för vibrationer från handhållna vibrerande verktyg. Syftet med avhandlingen var att studera om vibrationer i kombination med buller ökar risken för hörselnedsättning. Avhandlingen består av fyra studier. Den första studien är en experimentell studie med 22 friska deltagare med god hörsel. Denna studie undersökte hur hörseln tillfälligt påverkas av buller och vibrationer, separat och i kombination. Den andra och tredje studien bygger på en population bestående av 189 verkstadsarbetare i Sundsvall som följts regelbundet sedan 1987. Den andra studien undersökte om det finns en ökad risk för hörselnedsättning för arbetare som utsätts för buller och vibrationer under lång tid. Den tredje studien undersökte om arbetare med vita fingrar har en ökad risk för hörselnedsättning än arbetare utan vita fingrar. Vita fingrar är en kärlskada orsakad av vibrationer som gör att fingrarna reagerar onormalt snabbt på kyla. Fingrarna blir vita när blodtillförseln till dem stryps. Den fjärde studien är en enkätstudie med 342 kvinnor och män som har en bekräftad hörselnedsättning orsakad av buller. Studien undersökte hur många ur denna grupp som utsätts för vibrationer samt har vita fingrar. Resultaten från studierna visar att det inte finns någon skillnad i hörselpåverkan från buller och vibrationer i kombination jämfört med enbart buller under kort tid. De som utsätts för vibrationer från handhållna vibrerande verktyg i en bullrig miljö under lång tid har en ökad risk för hörselnedsättning. Arbetare med vita fingrar har en högre risk för hörselnedsättning än de utan. En hög andel av de med hörselnedsättning orsakad av buller använder sig av handhållna vibrerande verktyg. I studien fanns även en hög andel med vita fingrar. Sammanfattningsvis visar resultaten att det finns en långtidseffekt av buller och vibrationer på hörselnedsättning men inte någon korttidseffekt, och att vita fingrar kan påverka risken för hörselnedsättning.

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Le bruit de la circulation routière, et en particulier le bruit des deux-roues motorisés, constituent une importante source de gêne sonore. Afin d’estimer l’exposition sonore dans les villes de plus 100 000 habitants, la directive européenne 2002/49/CE impose la réalisation de cartes de bruit stratégiques, basées sur l’indice Lden. Cet indice est également utilisé dans des relations exposition-réponse, afin de prédire les pourcentages de personnes gênées, notamment par le bruit du trafic routier. En couplant les cartes de bruit stratégiques et ces relations exposition-réponse, des cartes de gêne pourraient être établies. Toutefois, la pertinence de cet indice pour prédire la gêne due au bruit en milieu urbain est souvent remise en cause, car de nombreux facteurs acoustiques influents (e.g. les caractéristiques spectrales et temporelles) ne sont pas pris en compte par cet indice. Cette thèse vise à améliorer la caractérisation de la gêne due au bruit de trafic routier urbain en considérant différentes compositions de trafic et la présence des deux-roues motorisés. Dans ce but, des expériences sont menées en conditions contrôlées. Une première étude a porté sur l’influence de plusieurs facteurs acoustiques relatifs aux périodes de calme et aux bruits de passage de véhicules sur la gêne due au bruit de trafic routier urbain. Cette étude a conclu à l’influence de la présence de périodes de calme et du nombre de véhicules au sein du trafic routier urbain et à l’absence d’influence de l’ordre des véhicules routiers, de la position et de la durée des périodes de calme. Ces résultats ont été utilisés afin de mener la caractérisation physique et perceptive de différentes compositions de trafic routier urbain. La régression multi-niveau a été utilisée pour calculer la gêne, en considérant 1) des facteurs acoustiques influents à l’aide de combinaisons pertinentes d’indices et 2) un facteur non acoustique : la sensibilité au bruit. Dans les villes, le bruit routier est souvent entendu en situation de multi-exposition avec d’autres bruits. Dans le cadre de ces travaux de thèse, les situations de multi-exposition aux bruits routier et d’avion ont été étudiées. Pour cela, un travail semblable à celui mené pour le bruit de trafic routier urbain a été mené pour le bruit d’avion conduisant également à des combinaisons pertinentes d’indices. En vue de caractériser les gênes dues aux bruits de trafic routier et d’avion pour des situations de multi-exposition sonore, les données des précédentes expériences ainsi que celles d’une expérience conduite en situation de multi-exposition à ces bruits combinés ont été utilisées au travers d’une régression multi-niveau adaptée, comme cela a pu être mené dans la littérature. La régression multi-niveau a ainsi permis la proposition de modèles de gêne pour chaque source de bruit. Puis, la gêne totale due à des situations de multi-exposition à ces bruits a été étudiée, afin de mettre en évidence les phénomènes perceptifs mis en jeu. Des modèles de gêne totale ont été proposés, en utilisant les modèles de gêne due à chaque source. Enfin, les modèles de gêne obtenus pour chaque source et les modèles de gêne totale ont été confrontés aux données d’une enquête socio-acoustique. A cet effet, une méthodologie a été proposée afin d’estimer les différents indices des modèles à partir des valeurs du Lden, issues de cartes de bruit et utilisées pour définir l’exposition au bruit des personnes enquêtées. Cette confrontation a montré que les modèles proposés à partir d’expériences menées en laboratoire et couplés à la méthodologie d’estimation des indices à partir des valeurs du Lden permettent une bonne prédiction de la gêne in situ. / Road traffic noise, and in particular powered two-wheeler noise, constitute an important source of noise annoyance. In order to estimate the noise exposure in cities of more than 100 000 inhabitants, the European directive 2002/49/EC requires the elaboration of strategic noise maps, based on the Lden index. This index is also used in exposureresponse relationships, to predict the percentages of annoyed people, by road traffic noise for example. By coupling strategic noise maps and these exposure-response relationships, noise annoyance maps could be established. The relevance of this index to predict noise annoyance in cities is however often questioned, since many influential acoustical factors (e.g. spectral and temporal features) are not considered by this index. The aim of this thesis is to enhance the characterization of noise annoyance due to different compositions of urban road traffic including powered two-wheelers. To achieve this goal, experiments were carried out under controlled conditions. A first study concerned the influence of several acoustical features related to quiet periods and vehicle pass-by noises on the annoyance due to urban road traffic noise. This study demonstrated the influence of the presence of quiet periods and of the number of vehicles within the urban road traffic and to the absence of the influence of the order of the vehicle pass-by noises, the position and duration of quiet periods. These results were used to carry out the physical and perceptual characterization of different compositions of urban road traffic noise. Multilevel regression was used to calculate noise annoyance, by coupling combinations of indices relating to influential acoustical features and an individual factor: noise sensitivity. In cities, road traffic noise is often combined with other noises. In the framework of this thesis, noise exposure to road traffic noise combined with aircraft noise was studied. Therefore, the same work as the one performed for urban road traffic noise was carried out for aircraft noise, leading also to relevant combinations of noise indices. In order to characterize annoyances due to road traffic noise and to aircraft noise in a combined exposure situation, data from the previous experiments and from an experiment dealing with these combined noises were used through an appropriate multilevel regression, as done in literature. The regression allows annoyance models for each noise source to be proposed. Then, total annoyance due to combined noises was studied, in order to highlight the perceptual phenomena related to the combined exposure. Total noise annoyance models were proposed, using proposed annoyance model of each noise source. Finally, these single source annoyance models and total annoyance models were tested using data of a socio-acoustic survey. To do this, a methodology has been proposed to estimate the different indices involved in the annoyance models, from the Lden values obtained from the strategic noise maps and used to define the noise exposure of the respondents. This confrontation showed that the models proposed on the basis of experiments carried out under laboratory conditions and coupled with a methodology of estimation of the noise indices from Lden values, enabled a good prediction of in situ annoyance.