The solubilities of benzene, naphthalene and anthracene were measured in five binary solvent systems. These systems consised of water and one of the following water miscible organic solvents: acetone, acetonitrile, methanol, ethanol, and isopropanol. The measurements were made at intervals of 0.1 volume fractions of the organic cosolvent. Solubility data were also collected for the above solutes in mixed cosolvents. solvent systems containing three In addition, the solubilities of and six five other aromatic solutes were measured in the binary solvent systems of methanol/water and acetone/water. The data was used to test the log-linear solubility model of Yalkowsky (1981). The model predicts a linear relationship between the solubility of a solute in a binary solvent system (S(m)) and the volume fraction of cosolvent present (f(c)) log S(m) = σf(c) + log S(w) Where S(w) is the solubility of the solute in water and σ is the proportionality constant and slope of the curve. The model is easily extended to multiple mixed solvents by combining the σ values from the binary solvent systems. log (S(m)/S(w)) = Σ₁ (σ₁£₁) A method was developed to estimate σ in a given binary solvent system from the octanol-water partition coefficient of the solute. Combining this method with the generalized solubility equation of Yalkowsky to estimate S(w), allows a priori estimates of solubility in mixed solvents. Maximum deviations in the binary solvent systems studied were related to maxima in excess density. In the alcoholic binary solvent systems the minima were related to minima in the heats of mixing of the two cosolvents. The herbicide atrazine deviated dramatically from the model. The system was examined for possible changes in the crystal structure of atrazine. It was found that some crystal modification occured in the presence of mixed solvents. The rate of the change appears to be dependant on the concentration of the cosolvent. A change or modification in the crystal violates one of the basic assumptions of the log-linear model. The assumption is that the crystal contributes equally to the solubility behavior irrespective of the solvent system. It was determined that atrazine undergoes a polymorphic transition in the systems studied. It is postulated that this polymorphism is responsible for the anomolous solubility behavior observed for atrazine.

Each year over 260,000 new cases of breast cancer will be diagnosed in the U.S. and approximately 40,000 women will die of metastatic breast cancer. The etiology of breast cancer is poorly understood and only 5 -10% of cases can be attributed to genetic factors. This suggests that the development of breast cancer may involve environmental factors including diet, lifestyle, and exposure to chemicals. Several lines of experimental and epidemiological evidence have highlighted COX-2 as a potential target for breast cancer prevention. The central hypothesis of this proposal is that activation of COX-2 transcription by epigenetic effectors can be prevented by dietary agents that target the activator protein-1 (AP-1) transcription factor and the aromatic hydrocarbon receptor (AhR). The first specific aim was to determine the mechanism through which conjugated linoleic acid (CLA) and rosmarinic acid (RA) inhibit TPA-induced COX-2 trancription. These studies documented that CLA and RA repressed COX-2 transcription by antagonizing the AP-1 transcription factor. The second specific aim was to investigate whether or not the AhR plays a role in TCDD-induced COX-2 transcription and effects of chemopreventive agents. Results indicated that AhR agonists induced the binding of the AhR to COX-2 and was prevented by CLA and the AhR antagonist, resveratrol (RES) and 3-methoxy-4-nitroflavone (3M4NF). The third specific aim was to examine the effects of AhR agonists and dietary selective AhR modulators on chromatin modifications associated with the COX-2 promoter. Chromatin immunoprecipitation (ChIP) assays revealed that the AhR is recruited to the region of the COX-2 promoter containing a xenobiotic response element and accompanied by recruitment of p300 and acetylation of histone H4. Transcriptional regulation of COX-2 by AhR agonists and dietary antagonists may also involve other post-transcriptional modifications of histones, which along with chromatin remodeling factors modulate the structure of chromatin and recruitment of RNA polymerase II. Overall, the results demonstrated that COX-2 transcription can be targeted by a variety of dietary agents that act through different mechanisms. Therefore, inhibition of transcriptional regulation of COX-2 by selected dietary factors may be a breast cancer preventive strategy that bypasses the side effects of drugs that target COX-2.

Breast cancer is the second leading cause of cancer-related death in women. Mutations in the tumor suppressor gene BRCA-1 confer a high risk of breast tumor development. However, in sporadic breast cancers, which represent 90-95% of breast cancer cases, BRCA-1 expression is downregulated in the absence of mutations in the BRCA-1 gene. This suggests that epigenetic effectors may contribute to disruption of BRCA-1 expression and the onset of mammary tumors.Prototypical environmental contaminants found in industrial pollution, tobacco smoke, and cooked foods include benzo[a]pyrene (B[a]P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which have been shown to alter mammary gland development, act as endocrine disruptors and tumor promoters. Population studies detected accumulation of TCDD in women's adipose tissue and breast milk. Moreover, sporadic breast tissue exhibited statistically significant higher levels of PAH-DNA adducts. Based on this information, we examined the effect of B[a]P on the tumor suppressor BRCA-1and observed that exposure to B[a]P led to repression of BRCA-1 transcription through a p53-dependent mechanism. We have also demonstrated that 17β-estradiol (E2) stimulated the recruitment of ERα and AP-1 family members to a region of the BRCA-1 promoter flanking an AP-1-like site. However, accumulation of p53 prevented E2-mediated BRCA-1 transcription and recruitment of ERα, potentially providing one mechanism of B[a]P-mediated repression.In addition, the effects of B[a]P and TCDD are mediated through binding of the liganded aromatic hydrocarbon receptor (AhR) to dioxin or xenobiotic-responsive elements (XRE). We have evidence that suggests B[a]P and TCDD may modulate repression of E2-stimulated BRCA-1 expression through 1) binding of the liganded AhR to XREs on the BRCA-1 promoter and 2) preventing promoter occupancy by p300 and SRC-1.Taken together, the data presented here suggest that the transcriptional regulation of BRCA-1 is complex and involves modulation of the recruitment of ERα, AhR, p53, and their cofactors. An important implication of these findings is a greater understanding of the role of ERα, AhR, and p53 in regulation of BRCA-1 which could lead to the development of therapeutic strategies that target these interactions to enhance upregulation of BRCA-1 expression in sporadic breast tumors.

Epigenetic mechanisms may contribute to reduced expression of the tumor suppressor gene BRCA-1 in sporadic breast cancers. Through environmental exposure and diet, humans are exposed to xenobiotics and food compounds that bind the aromatic hydrocarbon receptor (AhR). AhR-ligands include the dioxin-like and tumor promoter 2,3,7,8 tetrachlorobenzo-p-dioxin (TCDD). The activated AhR regulates transcription through binding to xenobiotic response elements (XRE=GCGTG) and interactions with transcription cofactors. Previously, we reported on the presence of several XRE in the proximal BRCA-1 promoter, and that the expression of endogenous AhR was required for silencing of BRCA-1 expression by TCDD. Here, we document that in estrogen receptor-alpha-positive and BRCA-1 wild-type MCF-7 breast cancer cells, the treatment with TCDD attenuated 17-beta estradiol (E2)-dependent stimulation of BRCA-1 protein and induced hypermethylation of a CpG island spanning the BRCA-1 transcriptional start site of exon-1a. Additionally, we found that TCDD enhanced the association of the AhR, DNA methyl transferases (DNMT)1, DNMT3a, and DNMT3b; methyl binding protein (MBD)2; and tri-methylated H3K9 (H3K9me3) with the BRCA-1 promoter. Conversely, the phytoalexin resveratrol, selected as a prototype dietary AhR antagonist, antagonized at physiologically relevant doses the TCDD-induced repression of BRCA-1 protein, BRCA-1 promoter methylation, and the recruitment of the AhR, MBD2, H3K9me3, and DNMTs (1, 3a, and 3b). Taken together, these observations provide evidence for a mechanistic role for AhR-agonists in establishment of BRCA-1 promoter hypermethylation and the basis for the development of prevention strategies based on AhR antagonists.

No description available.

The environmental fate of polycyclic aromatic hydrocarbons (PAH) is a significant issue, raising interest in bioremediation. However, the physio-chemical characteristics of PAHs and the physical, chemical, and biological properties of soils can drastically influence in the degradation. Moreover, PAHs are toxic and carcinogenic for humans and their rapid degradation is of great importance. The process of degradation of pollutants can be enhanced by manipulating abiotic factors. The effect of soil pH on degradation of PAHs with a view to manipulating soil pH to enhance the bioremediation of PAH’s was studied. The degradation rate of key model PAHs (Phenanthrene, Anthracene, Fluoranthene, and Pyrene) was monitored in J Arthur Brower’s topsoil modified to a range of pH between pH 4.0 and pH 9.0 at half pH intervals. Photo-catalytic oxidation of PAHs in the presence of a catalyst (TiO2) under UV light at two different wavelengths was studied. The degradation of PAHs during photo-catalytic oxidation was carried out at varying soil pH, whilst the degradation rate of each individual PAH was monitored using HPLC. It was observed that pH 6.5 was most suitable for the photo-degradation of all the PAHs, whilst in general acidic soil had greater photo-degradation rates than alkaline soil pH. Photo-degradation of PAHs at 375 nm exhibited greater degradation rates compared to 254 nm. Phenanthrene at both the wavelengths had greater degradation rate and pyrene has lower degradation rate of the four PAHs. Pure microbial cultures were isolated from road-side soil by shaken enrichment culture and characterized for their ability to grow on PAHs. Bacterial PAH degraders, isolated via enrichment were identified biochemically and by molecular techniques using PCR amplification and sequencing of 16S rDNA. Sequences were analyzed using BLAST (NCBI) and their percentage identity to known bacterial rDNA sequences in the GeneBank database (NCBI) was compared. The 6 bacterial strains were identified as Pseudomonas putida, Achromobacter xylosoxidans, Microbacterium sp., Alpha proteobacterium, Brevundimonas sp., Bradyrhizobium sp. Similarly, fungal PAH degraders were identified microscopically and with molecular techniques using PCR amplification and sequencing of 18S rDNA and identified as Aspergillus niger and Penicillium freii. Biodegradation of four PAHs with two and four aromatic rings were studied in soil with inoculation of the six identified bacteria and two identified fungi over a range of pH. It was observed that pH 7.5 was most suitable for the degradation of all the PAHs maintained in the dark. A degradation of 50% was observed in soil pH 7.5 within first three days which was a seventh of the time taken at pH 5.0 and pH 6.5 (21 days). Greater fungal populations were found at acidic soil pH and alkaline soil pH, in comparison with neutral pH 7.0. Pencillium sp. was found to be more prevalent at acidic pH whilst Aspergillus sp. was found to be more prevalent at pH 7.5-8.0. Bacterial populations were greater at pH 7.5 which was highly correlated with soil ATP levels. It was therefore evident that the greatest rates of degradation were associated with the greatest bacterial population. Soil enzyme activities in general were also greatest at pH 7.5. The converse effect of pH was found with fastest rate of photo-catalytic degradation at the optimal conditions were observed at acidic condition in soil pH 6.5 whilst, the results obtained during biodegradation at the optimal conditions exhibits fastest rate of degradation at alkaline conditions particularly at pH 7.5. Thus, manipulation of soil pH to 7.5 has significant potential to dramatically increase the degradation rate of PAHs.

The luminescence properties of Van Der Waals' dimers and clusters of pyrene and diazapyrene have been investigated. Excimers, dimeric species which are associative in an excited electronic state and dissociative in their ground state, have long been established and play an important role in many areas of photochemistry. My work here focuses on the luminescence and absorption properties of ground state dimers/aggregates, which are less understood, and allows further characterization of the ground state and excited state association of these aromatic molecules.

Detection, identification and separation of polycyclic aromatic compounds in environmental samples are of extreme importance since many of these compounds are well known for their potential carcinogenic and/or mutagenic activities. Selective quenching of molecular fluorescence can be utilized effectively to analyze mixtures containing different polycyclic aromatic hydrocarbons. Molecularly organized assemblies are used widely in detection and separation of these compounds mainly because of less toxicity and enhanced solubilization capabilities associated with these media. Feasibility of using nitromethane and the alkylpyridinium cation as selective fluorescence quenching agents for discriminating between alternant versus nonalternant polycyclic aromatic hydrocarbons (PAHs) is critically examined in several molecularly organized micellar solvent media. Fluorescence quenching is used to probe the structural features in mixed micelles containing the various combinations of anionic, cationic, nonionic and zwitterionic surfactants. Experimental results provide valuable information regarding molecular interactions between the dissimilar surfactants.

Appendices data can be found at: A: http://dx.doi.org/10.15142/T35P49 B: http://dx.doi.org/10.15142/T3201B C: http://dx.doi.org/10.15142/T3X59V D: http://dx.doi.org/10.15142/T3SG6K F: http://dx.doi.org/10.15142/T3NP4N

Le Bassin d’Arcachon est une lagune très riche écologiquement et suscite un attrait touristique et ostréicole important. Cette pression anthropique a soulevé ces dernières années des questions sociétales quant à sa qualité environnementale. Ainsi, ancrés dans des projets soutenus par les acteurs locaux (Région Aquitaine, Syndicat Intercommunal du Bassin d’Arcachon, Conseil général de la Gironde), ces travaux de thèse ont permis de dresser un bilan de la qualité de ce système et de ses bassins versants relativement à l’introduction des hydrocarbures aromatiques polycycliques (substances prioritaires selon la directive cadre sur l’eau, UE, 2000). Ces polluants organiques sont présents dans les différents compartiments environnementaux suivis (sédiments, colonne d’eau) de la lagune, en concentrations élevées pour quelques sites et pouvant induire des effets toxiques chez le biota aquatique. Ils sont généralement présents dans les eaux et sédiments des tributaires à un niveau bruit de fond, mais des concentrations importantes ont été observées pour un ruisseau, ainsi que lors d’un évènement de tempête. Ils sont principalement issus des processus de combustion incomplète de matières organiques (gaz d’échappement, chauffage, feux de forêt) ; des apports terrigènes et diagénétiques de pérylène ont également pu être mis en évidence. Les transferts des HAP vers le biota benthique (huître), et leur bioaccumulation sont effectifs malgré des capacités de dépuration importante relativement à d’autres classes de composés organiques hydrophobes. Comme alerté par le réseau national d’observation coordonné par IFREMER, les teneurs dans les organismes augmentent depuis une dizaine d’année, et s’approchent aujourd’hui de la valeur guide AFSSA pour la consommation humaine. Outre l’aspect de qualité environnementale, ces résultats peuvent apporter des informations quant aux problématiques nationales actuelles de surveillance chimique des productions conchylicoles (DGAL, 2008 ; AFSSA, 2008). / Abstract