THE RELATION BETWEEN BIOMARKERS AND OCCUPATIONAL EXPOSURE TO POLYCYCLIC AROMATIC COMPOUNDS

Recently a paper was published in which we reviewed a number of studies involving occupational surveys, where both the external polycyclic aromatic hydrocarbon (PAH) exposures and one or more biomarkers were quantitatively monitored. As part of that review a statistical analysis of the results of these studies was performed, which revealed that only urinary 1-hydroxypyrene (1OHPy) and possibly chromosome aberrations (CA) showed a correlation with PAH exposure, while unexpectedly, DNA adducts did not. Another observation was that although in controlled laboratory experiments good correlations have been found to occur between DNA adducts and exposure doses to polycyclic aromatic compounds (PACs), such a correlation was not found in the human occupational exposure studies reviewed. Also the analyses showed that sister chromatid exchanges (SCE) and micronuclei (MN) exhibited a very weak or an absence of a correlation, respectively, with external PAH exposure. The subject of this article is an attempt to explain: (a) why the levels of only some biomarkers correlate with PAH exposures and (b) the differences in results between controlled animal experiments and human monitoring studies.     

Reactions of Metal Ion Complexes with Lignin Model Compounds,Part II. Fe(TSPC) Catalyzed Formation of Oxidized Products in the Absence of Oxygen

The water soluble phthalocyanine complex trisodium tetra-4-sulfonatophthalocyanineiron(III) (Fe(TSPc)) was found to be an effective catalyst for the cleavage of the β-ether bonds in the phenolic lignin model compounds guaiacylglycol β-guaiacyl ether (1) and guaiacylglycerol β-guaiacyl ether (11). The products of these reactions were very different from those formed in the corresponding reactions catalyzed by anthraquinone (AQ) or Co(SPP).^1–4 In particular, they gave large quantities of oxidized products, even though the reactions were performed in the absence of oxygen or other added oxidant. Mechanisms have been proposed for the oxidation reactions involving 1 and 11. In both cases the first step involves one electron oxidation of the lignin model compound by the catalyst. The radical derived from 1 then undergoes further one electron oxidation and deprotonation to give 4′-hydroxy-3′-methoxy-l-(2″-methoxyphenoxy)acetophenone (8) whereas that derived from 11 undergoes Cα-Cβ bond cleavage to give vanillin (4). Reactions of the reduced form of the catalyst with 8 and the quinone methides produced from the phenolic models are important routes for guaiacol formation and regeneration of the oxidized form of the catalyst. The feasibility of these proposed reaction pathways was investigated by studying the reactions of the intermediate compounds with the catalyst.     

Transparent, flexible, conductive carbon nanotube coatings for electrostatic charge mitigation

Low color, space environmentally durable polymeric films with sufficient electrical conductivity to mitigate electrostatic charge (ESC) build-up are needed for applications on advanced spacecraft, particularly on large, ultra-light weight space structures. For these applications, the films must exhibit electrical conductivity that can survive the folding and unfolding required for packaging and deployment. The work described herein consists of coating the surface of polymer films with a thin layer of single-walled carbon nanotubes (SWNTs). Surface resistivities in the range sufficient for ESC mitigation were achieved with minimal effects on the optical and thermo-optical properties of the films. Bending, folding or crumpling did not affect the surface resistivity of the coated films. The preparation and characterization of SWNT coated space durable polymer films are discussed.     

Comparison of Antifungal and Antioxidant Activities of <Emphasis Type="Italic">Acacia mangium</Emphasis> and <Emphasis Type="Italic">A. auriculiformis</Emphasis> Heartwood Extracts

The effect of heartwood extracts from Acacia mangium (heartrot-susceptible) and A. auriculiformis (heartrot-resistant) was examined on the growth of wood rotting fungi with in vitro assays. A. auriculiformis heartwood extracts had higher antifungal activity than A. mangium. The compounds 3,4,7,8-tetrahydroxyflavanone and teracacidin (the most abundant flavonoids in both species) showed antifungal activity. A. auriculiformis contained higher levels of these flavonoids (3.5- and 43-fold higher, respectively) than A. mangium. This suggests that higher levels of these compounds may contribute to heartrot resistance. Furthermore, both flavonoids had strong 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and laccase inhibition. This suggests that the antifungal mechanism of these compounds may involve inhibition of fungal growth by quenching of free radicals produced by the extracellular fungal enzyme laccase.     

Properties of phyllosilicate-based porous ceramics shaped by conventional tape casting and freeze tape casting

Silicate ceramics were shaped using tape casting (TC) and freeze tape casting (FTC) processes from three clays labeled HCR, KORS, and KCR. These clays exhibited mass content of 77% halloysite–10 Å, 29% kaolinite, and 98% kaolinite minerals, respectively. After casting the slurries, the dried tapes were sintered at 1200°C. The microstructure changes were characterized before and after sintering using scanning electron microscopy. The apparent porosity of TC samples was lower (36–47 vol.%) compared to values obtained with FTC samples (67–79 vol.%). The latter samples exhibited a highly textured porosity, with micron-sized pores aligned perpendicular to the tape surfaces. Upon sintering, the porosity of TC samples tended to decrease conversely to the case of FTC samples. Such behavior seemed related to the simultaneous effect of organic additives and ice templating. Consequently, the FTC samples showed a relatively low mechanical strength of 3–7 MPa and thermal conductivity of .14– .22 W m⁻¹ K⁻¹. After sintering, the mullite crystallization contributed to strengthen the bulk materials, helping to compensate for the detrimental effect of porosity on the stress to rupture and on thermal conductivity values.     

Structure-activity relationship for the first-in-class clinical steroid sulfatase inhibitor Irosustat (STX64, BN83495)

Structure–activity relationship studies were conducted on Irosustat (STX64, BN83495), the first steroid sulfatase (STS) inhibitor to enter diverse clinical trials for patients with advanced hormone‐dependent cancer. The size of its aliphatic ring was expanded; its sulfamate group was N,N‐dimethylated, relocated to another position and flanked by an adjacent methoxy group; and series of quinolin‐2(1H)‐one and quinoline derivatives of Irosustat were explored. The STS inhibitory activities of the synthesised compounds were assessed in a preparation of JEG‐3 cells. Stepwise enlargement of the aliphatic ring from 7 to 11 members increases potency, although a further increase in ring size is detrimental. The best STS inhibitors in vitro had IC₅₀ values between 0.015 and 0.025 nM . Other modifications made to Irosustat were found to either abolish or significantly weaken its activity. An azomethine adduct of Irosustat with N,N‐dimethylformamide (DMF) was isolated, and crystal structures of Irosustat and this adduct were determined. Docking studies were conducted to explore the potential interactions between compounds and the active site of STS, and suggest a sulfamoyl group transfer to formylglycine 75 during the inactivation mechanism.     

Aromatase and dual aromatase-steroid sulfatase inhibitors from the letrozole and vorozole templates

Concurrent inhibition of aromatase and steroid sulfatase (STS) may provide a more effective treatment for hormone‐dependent breast cancer than monotherapy against individual enzymes, and several dual aromatase–sulfatase inhibitors (DASIs) have been reported. Three aromatase inhibitors with sub‐nanomolar potency, better than the benchmark agent letrozole, were designed. To further explore the DASI concept, a new series of letrozole‐derived sulfamates and a vorozole‐based sulfamate were designed and biologically evaluated in JEG‐3 cells to reveal structure–activity relationships. Amongst achiral and racemic compounds, 2‐bromo‐4‐(2‐(4‐cyanophenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)ethyl)phenyl sulfamate is the most potent DASI (aromatase: IC₅₀=0.87 nM ; STS: IC₅₀=593 nM ). The enantiomers of the phenolic precursor to this compound were separated by chiral HPLC and their absolute configuration determined by X‐ray crystallography. Following conversion to their corresponding sulfamates, the S‐(+)‐enantiomer was found to inhibit aromatase and sulfatase most potently (aromatase: IC₅₀=0.52 nM ; STS: IC₅₀=280 nM ). The docking of each enantiomer and other ligands into the aromatase and sulfatase active sites was also investigated.     

Anodic behaviour of oxidised Ni–Fe alloys in cryolite–alumina melts

Nickel-iron alloys have been identified as promising inert anode candidates for the Hall–Héroult process. In this study, binary Ni–Fe alloys of various compositions were subjected to short-term galvanostatic electrolysis in a cryolite–alumina bath at 960 °C. Prior to electrolysis, the anodes were oxidised at 800 °C for 48 h, forming a protective scale. Fe₂O₃, Ni_xFe_3−xO₄ and Ni_xFe_{1 − x}O were identified as the major scale components using a combination of X-ray diffraction (XRD) analysis and energy dispersive X-ray spectroscopy (EDX). Anodes having Ni content of 50–65 wt% performed adequately during short-term electrolysis, operating at a steady potential of 3–3.5 V vs. AlF₃/Al. Overall, it was found that the pre-formed oxide scale was effective in reducing anode wear and fluoridation. In the absence of a pre-formed scale, anodes were shown to undergo appreciable internal corrosion and/or passivation due to metal fluoride formation. Analysis of the anodes following electrolysis was performed using XRD and electron microprobe analysis (EPMA).