2-Chloroethyl ethyl sulfide (CEES) or half-mustard gas, a sulfur mustard (HD) analog, is a genotoxic agent that causes oxidative stress and induces both apoptotic and necrotic cell death. Sodium pyruvate induced a necrosis-to-apoptosis shift in HaCaT cells exposed to CEES levels ≥ 1.5 mmol/L and lowered markers of DNA damage, oxidative stress, and inflammation. This study provides a rationale for the future development of multicomponent therapies for HD toxicity in the skin. We hypothesize that a combination of pyruvates with scavengers/antioxidants encapsulated in liposomes for optimal local delivery should be therapeutically beneficial against HD-induced skin injury. However, the latter suggestion should be verified in animal models exposed to HD.

Indiana University-Purdue University Indianapolis (IUPUI) / Invasive exotic species have caused severe ecological and economic damages to many communities in the United States and elsewhere. It is therefore important to improve our understanding of how global environmental changes will affect the invasiveness and severity of these invasive species. Over the last century, anthropogenic activities have caused multiple environmental changes. Previous studies have generally focused on the impact of the increasing atmospheric CO2 level on the physiology and growth of invasive species. With atmospheric nitrogen (N) deposition on the rise over the past decades, it is essential to recognize how an increase in soil N will affect the invasiveness of some exotic species. To determine the impact of increased atmospheric N deposition and drought stress on invasive species, I studied the impact of different levels of N on Alliaria petiolata (garlic mustard), an exotic invasive species. In addition, I examined the interactive effects of N deposition and drought stress on garlic mustard. Multiple morphological measurements were used to analyze the growth rate at varying levels of N and soil moisture. The study on N deposition on plant growth will improve our understanding of the invasiveness of garlic mustard. The changes in precipitation patterns must also be examined to foresee if plants in increased atmospheric N conditions can overcome drought stress conditions. I found an increase in plant growth and photosynthetic rate at higher levels of N. Plants with adequate water displayed a continued increase from the lowest level to the highest level of N. Increases in drought stressed plants plateaued at an intermediate N level of 20 kg ha-1. My results demonstrated that during drought stress garlic mustard does not benefit from an increase in N above a certain level. These results are important to take into consideration when we analyze the spreading of invasive weeds due to global environmental changes, including increased atmospheric N deposition and regional drought, in order to apply the optimal management strategies for controlling invasive species.

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Garlic mustard (Alliaria petiolata, Brassicaceae) is a biennial herb that produces glucosinolates, a class of constituent secondary metabolites that defend against herbivores and pathogens allowing it to grow at high densities in invaded regions. The glucosinolate sinigrin is predominant in garlic mustard and aids in its competitiveness as an invasive species. In North America, garlic mustard can grow at high densities and form dense monocultures which may increase its apparency to herbivores and therefore increase its sinigrin production. I measured leaf sinigrin concentration in garlic mustard populations of different densities in the field and in greenhouse experiments to evaluate the response of sinigrin concentration and growth to density and light. Sinigrin concentrations of second-year plants were negatively correlated with growth metrics across all field densities; indicating a cost to sinigrin production. In the greenhouse density experiment with high and low rosette stem densities, sinigrin differed significantly by rosette density category. A factorial greenhouse experiment with light and density treatments discerned significant differences in sinigrin concentration by density. These findings suggest that sinigrin concentration may be influenced by intraspecific density across different light environments.

Causes and patterns of invasive plant species establishment and success depend broadly upon their ecology, including habitat suitability and interactions with other plants and animals. Here I examine the traits and distribution of invasive plants in Vermont, using spatial analysis, laboratory and field studies. I used GIS to investigate environmental factors correlated with presence of 19 invasive plant species in Vermont campgrounds. My results support the assumption that human dispersal of invasive plant seed and stock may be more important than natural dispersal of these plant species to new sites. I also investigate in-depth the relationships of invasive herbaceous garlic mustard (Alliaria petiolata) with native tree seedlings and co-occurring herbaceous plants in the greenhouse and Vermont forests, respectively. Shade from > 1 m tall A. petiolata plants may effect root:shoot ratios of neighboring tree seedlings and interact with nutrition quality of sites to affect their growth patterns. Invasive plants' integration into novel environments is also mediated by their interactions with native invertebrate species. A. petiolata is associated with a unique assemblage of aboveground invertebrates compared with neighboring native plants. Observations indicate A. petiolata may also serve as an attractant for ants, bees, and wasps who feed from water and nectar at the base of the flower or silique during its flowering and seeding period. These results collectively inform our understanding of plant invasion patterns and management strategies of A. petiolata in Vermont. Community interactions are probably more important than allelopathy in determining the influence of Alliaria petiolata on native ecosystems.

L'ypérite est une arme chimique de guerre de la famille des vésicants. Sa facilité de synthèse et l'existence de stocks importants dans le monde en font une menace à la fois pour les populations civiles et les militaires. Cette menace est renforcée par le fait qu'à l'heure actuelle il n'existe pas d'antidote efficace contre ce toxique de guerre. L'alkylation de l'ADN par l'ypérite aboutit à la formation d'adduits. L'objectif de cette thèse a consisté à mettre au point une méthode de détection quantificative de ces adduits par chromatographie liquide haute performance couplée à la spectrométrie de masse en tandem (HPLC-MS/MS) et d'appliquer cette méthode à l'étude de leur formation et de leur persistance après une exposition cutanée chez la souris SKH-1. Les résultats ont montré dans la peau exposée que la fréquence des adduits était maximale dès 6h post-exposition. Toutefois, leur persistance était relativement longue puisqu'ils étaient toujours détectables 3 semaines après exposition. Une diffusion radiale de l'ypérite a été mise en évidence par la détection des adduits qu'elle forme dans des échantillons de peau non directement exposés. Les adduits ont été également détectés dans plusieurs organes internes. La fréquence maximale des adduits a été mesurée 6h ou J1 post-exposition. Ils ont été décelés jusque J21 post-exposition. Les résultats ont montré qu'il se formait plus d'adduits dans le cerveau et les poumons que dans les reins, la rate et le foie. La persistance des adduits dans le cerveau et les poumons était moindre après la détersion de la peau exposée, illustrant ainsi la constitution dans cette dernière d'un réservoir d'ypérite. La mesure des activités de réparation de l'ADN a montré que l'ypérite exerçait une double action génotoxique, à savoir formation de dommages à l'ADN et inhibition des activités de réparation. / Sulphur mustard is a chemical warfare which belongs to the vesicants family. Its easy synthesis and the existence of important stocks in the world make it a threat for both the general population and militaries. This threat is reinforced by the fact that currently there is not efficient antidote against this war toxic. DNA alkylation by sulphur mustard leads to adducts formation. The objective of this thesis consisted in developing a method of quantification of these adducts by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) and to apply this method to the study of the formation and persistence of the adducts after cutaneous exposure in SKH-1 mouse. Results have shown in exposed skin that adducts frequency was maximal as soon as 6h post-exposure. A radial diffusion of sulphur mustard was highlighted by the detection of adducts it forms in skin samples non-directly exposed. Adducts were also detected in several internal organs. Maximal frequency was measured at 6h or d1 post-exposure. They were detected until d21 post-exposure. Results have shown that adducts were produced in larger amount in brain and lungs than in kidneys, spleen and liver. The persistence of adducts was lower in brain and lungs after the detersion of exposed skin, thus illustrating the constitution of a reservoir of sulphur mustard in this tissue. Measurement of DNA repair activities showed that suilphur mustard behave as a two-edge sword genotoxic, namely formation of DNA damages and inhibition of repair activities.

The objective of this study was to determine if the presence of two ALS inhibiting herbicide residues in three Saskatchewan soils would result in an additive, synergistic, or antagonistic interaction. This was determined through field trials where herbicides were applied sequentially over the course of two years and through dose-response modelling. The herbicides examined in these experiments were imazamethabenz, flucarbazone-sodium, sulfosulfuron, and florasulam, each in combination with imazamox/imazethapyr. The phytotoxicity and persistence of the herbicides in soil was assessed using an Oriental mustard root inhibition bioassay. The determination of herbicide interaction was made through the comparison of the experimentally observed values to theoretically expected values derived from a mathematical equation.<p>The dose response curves created by placing incremental concentrations of these herbicides in soil were compared using the I50 parameter, which is the concentration resulting in a 50% reduction in root length. It appeared that soil organic matter followed by soil pH had the greatest effect in reducing herbicide residue phytotoxicity in the tested soils. Based on the bioassay analysis of sequentially applied ALS inhibiting herbicides, it is proposed that the phytotoxic effect of herbicide residues in soil result in additive injury effects rather than synergistic or antagonistic interactions.