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.

Polycyclic aromatic hydrocarbon (PAH) compounds, which are common to coal tar and coal-tar-based products, are ubiquitous environmental contaminates with carcinogenic effects to human health and aquatic life. Transport of PAHs via solid phase particulate motion, gaseous phase volatilization, and aqueous phase dissolution into urban waterbodies of PAH compounds from coal-tar-based pavement sealant products has been studied. Pavement rejuvenators are products applied to increase the usable life of pavement. Coal-tar-based rejuvenators contain a significantly larger mass fraction of coal-tar with respect to coal-tar-based sealants, but pavement rejuvenators have not been as extensively studied as pavement sealants. Chemical analysis of detached pavement material treated with coal-tar-bases, asphalt-based, and bio-based rejuvenators was conducted with gas chromatography – mass spectrometry (GC/MS) analysis for 16 PAH compounds and two aromatic heterocyclic organic compounds following extraction with methylene chloride. Detached pavement material was collected from 19 simulated asphalt surface abrasion experiments that used a model mobile load simulator (MMLS) test apparatus that replicated surface challenges from vehicular traffic. The MMLS test apparatus configuration allowed asphalt disc samples treated with different rejuvenation products, to be tested and for detached material to be collected and quantified prior to GC/MS analysis. Test cases evaluated the influence of rejuvenation product type and cure time, as well as the effect of sand application (simulating sand application during slippery winter storm conditions) had on detached particulate and ultimate PAH compound loading. The average mass of particulate detachment from samples following a 48 hour cure time, for the asphalt-based and coal-tar-based rejuvenator products were 0.347 g and 0.480 g, respectively. This mass of detached material was lower than that from pavement treated with bio-based rejuvenator and the control (not treated), which had 4.858 g and 2.567 g of detached particulate material, respectively. When the product cure time was increased to three weeks, which was significantly long enough to capture effects of compound volatilization, average particulate detachment increased to 0.882 g for the coal-tar-based rejuvenator and decreased for the bio-based rejuvenator to 2.600 g. Six tests performed with a single application of winter storm sand after a 48 hour product cure time showed an increase in average particulate detachment to 1.450 g and 0.617 g for pavement treated with the asphalt-based and coal-tar-based rejuvenators, respectively. Conversely, under the same conditions, a reduction in average detached particulate to 3.749 g was observed for the bio-based product. Detached particulate material quantities for each test case were used with the respective cumulative concentration of 16 PAH compounds quantified to make an assessment on the potential PAH compound contamination via solid phase particle transport. The average PAH compound concentration in particulate detached from pavement treated with a coal-tar-based rejuvenator was 3062.8 mg PAH per kg of particulate. This was an order of magnitude higher than the average PAH concentration measured in particulate detached from the two control pavement samples and the two asphalt-based samples after a 48 hour cure time, which were 322.1 and 508.1 mg PAH per kg detached particulate, respectively. PAH compound concentrations were also normalized by the surface area of pavement treated with a rejuvenator to determine the potential PAH compound contamination per unit area. Normalized results for each rejuvenator type were averaged to make an overall evaluation of the potential rejuvenator specific PAH compound loading. The coal-tar-based, bio-based, and asphalt-based rejuvenators had a normalized cumulative solid-phase PAH compound release of 2.35, 0.88, and 0.17 mg PAH per square foot of pavement rejuvenated, respectively. In addition, carbazole was quantified in all pavement samples treated with the coal-tar-based rejuvenator at an average concentration of 125.6 mg carbazole per kg detached particulate. Acridine was quantified in detached particulate from five of seven coal-tar-based test performed at an average concentration (excluding non-detection samples) of 42.1 mg acridine per kg detached particulate.

Capping is typically used to control contaminant release from the underlying sediments. However, the presence of conventional caps often eliminates or slows natural degradation that might otherwise occur at the surface sediment. This is primarily due to the development of reducing conditions within the sediment that discourage hydrocarbon degradation. The objective of this study was to develop a novel active capping method, an electrode enhanced cap, to manipulate the redox potential to produce conditions more favorable for hydrocarbon degradation and evaluate the approach for the remediation of PAH contaminated sediment. A preliminary study of electrode enhanced biodegradation of PAH in sediment slurries showed that naphthalene and phenanthrene concentration decreased significantly within 4 days, and PAH degrading genes increased by almost 2 orders of magnitude. In a sediment microcosm more representative of expected field conditions, graphite cloth was used to form an anode at the sediment-cap interface and a similar cathode was placed a few centimeters above within a thin sand layer. With the application of 2V voltage, ORP increased and pH dropped around the anode reflecting water electrolysis. Various cap amendments (buffers) were employed to moderate pH changes. Bicarbonate was found to be the most effective in laboratory experiments but a slower dissolving buffer, e.g. siderite, may be more effective under field conditions. Phenanthrene concentration was found to decrease slowly with time in the vicinity of the anode. In the sediment at 0-1 cm below the anode, phenanthrene concentrations decreased to ~70% of initial concentration with no bicarbonate, and to ~50% with bicarbonate over ~70 days, whereas those in the control remained relatively constant. PAH degrading gene increased compared with control, providing microbial evidence of PAH biodegradation. A voltage-current relationship, which incorporated separation distance and the area of the electrodes, was established to predict current. A coupled reactive transport model was developed to simulate pH profiles and model results showed that pH is neutralized at the anode with upflowing groundwater seepage. This study demonstrated that electrode enhanced capping can be used to control redox potential in a sediment cap, provide microbial electron acceptors, and stimulate PAH degradation. / text

A collection of 4,10-chrysene derivatives was prepared via the BHQ (Bull-Hutchings- Quayle) reaction, their electronic and morphological properties analysed and assessed for suitability as organic semiconductor (OSC) materials. Larger polycyclic aromatic hydrocarbons (PAHs) such as benzo[k]tetraphenes and dinaphtho[1,2,-b:1',2'- k]chrysenes were then prepared and similarly characterised. An acene-based OSC material TMTES-pentacene was also prepared. It is proposed that non-linear PAH- based OSC materials may provide an alternative to popular acene-based materials; offering advantages in stability, diversity and handling.

Fireworks on Independence Day have been identified as a nationwide but short-term source of particulate matter in the U.S. No study has specifically examined their impacts on ambient polycyclic aromatic hydrocarbons (PAHs). Based on data between 1990 and 2019 in the Air Quality System, we identified 76 unique events that had PAH measurements on both July 4th days and control days (within 15 days before and after July 4th). We compared concentrations and diagnostic ratios of 16 priority PAHs between event and control days using Wilcoxon signed-rank tests and multivariable regressions. A local PAH monitoring campaign was conducted at eight sites in Memphis, Tennessee, to obtain a close observation of PAH changes. The national geometric mean (GM) concentrations of summed 16 PAHs (ΣPAHs) were similar between event and control days (48.1 ng/m3 vs. 52.8 ng/m3, p = 0.98). About a quarter of events had elevated PAH concentrations compared with control days. Higher diagnostic ratios were found on event days, suggesting more contributions from fireworks sources. PAHs on July 4th were unlikely to cause acute or chronic health effects. While the local monitoring showed a 15% increase of ΣPAHs on July 4th, the difference was not significant (p = 0.62). Elevated PAH concentrations occurred at sites near fireworks sources and without major traffics, but did not occur at those in remote areas or near major interstate highways. In conclusion, this study finds that Independence Day fireworks have negligible impacts on atmospheric PAHs at the national level, and are unlikely to pose significant health risks. The firework effect is localized within a limited geographic scale, suggesting potential needs for local monitoring and control programs.

Polycyclic aromatic hydrocarbons (PAH) are important environmental pollutants generally formed during incomplete combustion of organic matter containing carbon and hydrogen. Introduced into the human body by adsorption through the skin, ingestion or inhalation, the biotransformation processes of PAH lead to the formation of multiple metabolites. Due to the short elimination lifetime from the body, the quantitative determination of monohydroxy-PAH (OH-PAH) in urine samples provides accurate information on recent exposure to environmental PAH. Urine analysis of OH-PAH with established methodology relies on sample clean-up and pre-concentration followed by chromatographic separation and quantification. Although chromatographic techniques provide reliable results in the analysis of OH-PAH, their experimental procedures are time consuming and expensive. Additional problems arise when laboratory procedures are scaled up to handle thousands of samples under mass screening conditions. Under the prospective of a sustainable environment, the large usage of organic solvents is one of the main limitations of current chromatographic methodology. It is within this context that new analytical approaches based on easy-to-use and cost-effective methodology become extremely relevant. This dissertation focuses on the development of screening methodology for the routine analysis of PAH metabolites in numerous samples. It explores the room-temperature fluorescence properties of six metabolites originating from parent PAH included in the Environmental Protection Agency priority pollutants list. 1- hydroxyfluorene, 1-hydroxypyrene, 6-hydroxychrysene, 9-hydroxyphenanthrene, 3- hydroxybenzo[a]pyrene and 4-hydroxybenzo[a]pyrene are used as model biomarkers to investigate the analytical potential of new methods based on solid-phase extraction (SPE) and iii room-temperature fluorescence (RTF) spectroscopy. Quantitative determination of metabolites is carried out either in the eluent extract[1, 2] or on the surface of extraction membranes[3, 4] . The direct determination – i.e., no chromatographic separation - of the six metabolites is based on the collection of excitation-emission matrices and synchronous fluorescence spectra.

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京都大学 / 新制・課程博士 / 博士(工学) / 甲第23927号 / 工博第5014号 / 新制||工||1783(附属図書館) / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 松田 建児, 教授 杉野目 道紀, 教授 生越 友樹 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

Cross-conjugation in molecules has been seen in nature for many years but was not pursued due to the difficulty of their synthesis and their lack of stability. Recently, it has become more interesting due to the rise of molecular electronics. Linear conjugation serves well as the wires to conduct electrons, but molecular electronics are made up of more than just wires. Molecules are needed that possess an on/off switch that can allow or deter conduction. Cross-conjugated systems show promise in their ability to be turned on or off from external stimuli. Pentacene quinone is a well-known cross-conjugated molecule that already shows promise in the field of molecular semiconductors. By synthetically fusing the pentacene quinone to the β, β' positions of a porphyrin, it has been shown that both the solubility and stability have been greatly improved. This has allowed us to pursue functionalization of the quinone moiety. Several new cross-conjugated pentacene quinone fused porphyrin systems were synthesized and studied. It was found that cross-conjugated platinum porphyrins show enhanced fluorescence, and phosphorescence that shifts toward the Near IR. Additionally, strong electron withdrawing groups show potential in charge transfer, and a lower HOMO to LUMO gap, while mildly withdrawing groups have a higher HOMO to LUMO gap. Furthermore, a new method to introduce halogenated methine bridges at the pentacene quinone core was developed, thus opening the doors to new polycyclic aromatic hydrocarbons to be synthesized and studied.