Tyrphostin AG1024 downregulates aryl hydrocarbon receptor (AhR) expression in an IGF1R and IR-independent manner.

The aryl hydrocarbon receptor (AhR) is a receptor-type transcription factor that is crucial for endocrine disruption and carcinogenesis caused by environment chemicals. Previous studies have indicated that certain intracellular signals are involved in AhR activation by their agonists, but the detailed mechanism remains unclear. In this study, we screened for important molecules for AhR activation using SCAD inhibitor kits. Among 164 kinase inhibitors listed in these kits, tyrphostin AG1024, commonly used as an inhibitor of insulin-like growth factor receptor (IGF1R) and insulin receptor (IR), was identified as a potent inhibitor of 3-methylcholanthrene (MC)-mediated AhR activation. We further investigated the mechanism by which AG1024 suppresses MC-mediated AhR activation. AG1024 decreased AhR-dependent luciferase activity, CYP1A1 gene expression, and its protein expression. However, when IGF1R siRNA and IR siRNA were used, AhR activation was slightly increased, in contrast to AG1024 treatment. In addition, AG1024 treatment downregulated the expression of AhR protein but not AhR gene, and decreased both nucleic and cytosolic AhR proteins. Therefore, AG1024 suppressed AhR activation by downregulating AhR protein expression. The molecular target of AG1024 remains unclear, and should be an important target for the regulation of AhR-dependent toxicity.

Simultaneous Determination of Cr, As, Se, and Other Trace Metal Elements in Seawater by ICP-MS with Hybrid Simultaneous Preconcentration Combining Iron Hydroxide Coprecipitation and Solid Phase Extraction Using Chelating Resin.

In the present study, ICP-MS with a new hybrid simultaneous preconcentration combining solid phase extraction using chelating resin and iron hydroxide coprecipitation in one batch at a single pH adjustment (pH 6.0) were developed for multielement determination of trace metal ions in seawater. In multielement determination, the present method makes it possible to determine Cr(III), As(V), Se (IV), and other 14 trace metal elements (Ti, V, Co, Ni, Cu, Zn, Zr, Ge, Cd, Sb, Sn, W, Pb, and U) in seawater. Moreover, for speciation analyses of Cr, As, and Se, the pH dependence on recovery for the different chemical forms of Cr, As, and Se was investigated. In speciation analyses, Cr, As, and Se were determined as the total of Cr (III) and a part of Cr (VI), total of As (III) and As (V), and Se(IV), respectively. Determination of total of Se and Cr(VI) remains as future task to improve. Nevertheless, the present method would have possibility to develop as the analytical method to determine comprehensively most metal elements in all standard and guideline values in quality standard in environmental water in Japan, that is, most toxic metal elements in environmental water.

Composition and Elution Behavior of Various Elements from Printed Circuit Boards, Cathode-ray Tube Glass, and Liquid-crystal Displays in Waste Consumer Electronics.

The contents and elution behavior of metals in consumer electronics parts were determined so as to understand their maximum environmental risk. Elements contained most in printed-circuit boards were Cu, Si, Br, Ca, Al, Sn, Pb, Sb, Ba, Fe, Ni, Ti, and Zn; in cathode-ray tube glass were Si, Pb, Ba, Sr, Zn, Zr, Ca, and Sb; in arsenic contained liquid-crystal displays were Si, Ca, Sr, Ba, As, and Fe; and in antimony contained liquid-crystal displays were Si, Ba, Ca, Sb, Sr, Fe, and Sn. The elements eluted most from printed-circuit boards were Zn, Pb, and Cu; from cathode-ray tube glass were Pb, Zn, B, Ba, and Si; and from liquid-crystal displays were B and Si, and the toxic As and Sb. The amount eluted was greatest at acidic pH. It was revealed that officially recommended 6-h-shaking with a pure water test was insufficient to understand the real environmental risk of waste electronics.

Influence of GSH S-transferase on the mutagenicity induced by dichloromethane and 1,2-dichloropropane.

It has been suggested that dichloromethane (DCM) and 1,2-dichloropropane (DCP) are responsible for occupational cholangiocarcinoma. Dihaloalkanes are metabolically activated by GSH S-transferase theta1 (GSTT1) to yield products such as episulfonium ions. However, whether the GSTT1-mediated step of these dihaloalkanes is related to occupational cholangiocarcinoma is not known. In the present study, we investigated the influence of GSTT1 activation on the mutagenicity of DCM and 1,2-DCP using GSTT1-expressing Salmonella typhimurium TA100 (TA100-GST). Since the mutagenicity of DCM was significantly increased in TA100-GST compared with mock control (TA100-pCTC), GSTT1 is thought to be involved in the mutagenicity of DCM. Mutation spectrum analysis on the hisG gene revealed that C:G to A:T transversions were the predominant form observed in DCM-treated TA100-pCTC. However, C:G to T:A transitions were dramatically increased in TA100-GST. We also analysed the DCM-DNA adduct, N2-GSH-Me-dG, and formation of N2-GSH-Me-dG was increased in TA100-GST compared with TA100-pCTC. On the other hand, 1,2-DCP did not increase the numbers of revertants in TA100-GSTT1. In mutation spectrum analysis, C:G to T:A transitions was predominant in both TA100-pCTC and TA100-GSTT1. These findings suggest that GSTT1 has little involvement in DCP mutagenicity, and other mechanisms might be more important for bioactivation and consequent genotoxicity. Clarification of the mechanisms underlying the development of DCM- and/or 1,2-DCP-related human cholangiocarcinoma may help establish risk assessment and prevention strategies against occupational cancer.

Effects of substituents in ß-diketones and their tris-iron(III) complexes on partitioning between various micellar phases and the bulk aqueous phase.

To determine the factors that affect the partitioning of solutes in micellar systems, we investigated the partitioning of several ß-diketones and their tris-complexes with iron(III) between the bulk aqueous phase and micelles of various polyoxyethylene (POE)-type nonionic surfactants (C(12)POE(8), Brij 35, Brij 58, and Triton X-100). The trends of the partition constants in the micellar systems differed from those in typical liquid-liquid systems; these differences may have been due to the effects of the substituent groups on the extractants, and to the effects of the inner-sphere chemistry of the micelles. The bulkiness and the low wettability of the extractants and the complexes hindered their extraction into the micellar phase. The interaction between the polyoxyethylene moiety of the surfactants and water molecules dissolved in the micellar mantle may have hampered the penetration of such solutes with bulky or low-wettability substituents into the mantle. The locus of the solutes in the micelles seemed to play an important role in the partitioning behavior.

DNA microarray mediated transcriptional profiling of Nitrosomonas europaea in response to linear alkylbenzene sulfonates.

Linear alkylbenzene sulfonates (LAS) constitute, quantitatively, the most important group of synthetic surfactants used today. We studied the gene expression of Nitrosomonas europaea in response to LAS using a DNA microarray because ammonia-oxidizers are thought to be more sensitive to LAS than other microorganisms. Our objective was to elucidate which genes are expressed for N. europaea in response to LAS exposure. Microarray analysis and real-time PCR assay revealed that c. 30 genes were significantly expressed after LAS exposure, in particular genes associated with energy production and conversion. Our findings demonstrate that physical disruption of membrane structures, which contain enzymes associated with energy production and conversion, might be an important explanation for the high sensitivity of N. europaea to LAS exposure.

Formation of bromo-substituted triclosan during chlorination by chlorine in the presence of trace levels of bromide.

The side reactions of triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether, TC) and chlorine in the presence of sodium chloride were investigated. In the absence of sodium chloride, three chloro-derivatives of TC, 2',3,4,4'-tetrachloro-2-hydroxydiphenyl ether (3-Cl-TC), 2',4,4',5-tetrachloro-2-hydroxydiphenyl ether (5-Cl-TC), and 2',3,4,4',5-pentachloro-2-hydroxydiphenyl ether (3,5-Cl(2)-TC) were formed, whereas in the presence of sodium chloride, 3-bromo-2',4,4'-trichloro-2-hydroxydiphenyl ether (3-Br-TC), 5-bromo-2',4,4'-trichloro-2-hydroxydiphenyl ether (5-Br-TC), (3 or 5)-bromo-2',4,4',(5 or 3)-chloro-2-hydroxydiphenyl ether ((3,5)-(BrCl)-TC), and 3,5-dibromo-2',4,4'-trichloro-2-hydroxydiphenyl ether (3,5-Br(2)-TC) were additionally formed. Radiochemical neutron activation analysis indicated that 1g of commercially available sodium chloride contained 73 microg of bromide and the bromide ion was determined to be the source of the side reactions. The rate of decrease of TC due to reaction with chlorine was greatly accelerated by the presence of bromide ion in the system: the rate with only 1 x 10(-5) M bromide ion was three times the rate in the absence of bromide.

Transfer rate of several tris(beta-diketonato)iron(III) complexes at the bulk aqueous--Triton X-100 micellar interface: effects of substituent groups in the extractants.

The transfer rate of tris(beta-diketonato)iron(III) complexes with acetylacetone, benzoylacetone, trifluoroacetylacetone, benzoyltrifluoroacetone, and 2-thenoyltrifluoroacetone at the water-Triton X-100 micellar interface was measured by stopped-flow spectrophotometry. The forward transfer rate was first-order with respect to the micellar concentration; the rate-determining step was concluded to be the capturing process of the collided complex at the micellar surface. The value of the rate constant varied with the substituent groups in the extractants; several effects of the substituent groups on the transfer rate were observed. The "mantlephobicity" of the trifluoromethyl group because of its low wettability, the hydrophobicity of the phenyl and thienyl groups in light of their bulkiness, the dilution of the negative efficiency of the trifluoromethyl group at the capturing by enlarging the complex surface with these bulky groups, and the "mantlephilicity" of the thienyl group from its interaction with the hydrogen-bonded network of the micellar "mantle" were estimated. In contrast, the backward rate was independent of the micellar concentration, and the order could be explained by the distribution of the tris-complexes between the "core" and "mantle" of the micelle. The "core-mantle" double-layer structure of the micelle would be an important key for the behavior at the interface.