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In the field of gene expression analysis, DNA microarray technology has a major impact on many different areas including toxicogenomics, such as in predicting the adverse effects of new drug candidates and improving the process of risk assessment and safety evaluation. In this study, we investigated whether there is relationship between the hepatotoxic phenotypes and gene expression profiles of hepatotoxic chemicals measured by DNA microarray analyses. Sprague-Dawley rats (6 weeks old) were administered five hepatotoxicants: acetaminophen (APAP), bromobenzene, carbon tetrachloride, dimethylnitrosamine, and thioacetamide. Serum biochemical markers for liver toxicity were measured to estimate the maximal toxic time of each chemical. Hepatic mRNA was isolated, and the gene expression profiles were analyzed by DNA microarray containing 1,097 drug response genes, such as cytochrome P450s, other phase I and phase II enzymes, nuclear receptors, signal transducers, and transporters. All the chemicals tested generated specific gene expression patterns. APAP was sorted to a different cluster from the other four chemicals. From the gene expression profiles and maximal toxic time estimated by serum biochemical markers, we identified 10 up-regulated genes and 10 down-regulated genes as potential markers of hepatotoxicity. By Quality-Threshold (QT) clustering analysis, we identified major up- and down-regulated expression patterns in each group. Interestingly, the average gene expression patterns from the QT clustering were correlated with the mean value profiles from the biochemical markers. Furthermore, this correlation was observed at any extent of hepatotoxicity. In this study, we identified 17 potential toxicity markers, and those expression profiles could estimate the maximal toxic time independently of the hepatotoxicity levels. This expression profile analysis could be one of the useful tools for evaluating a potential hepatotoxicant in the drug development process.

Fluorescence and absorption spectra of 14 arylpentamethyldisilanes and related compounds are recorded. Several compounds reveal dual fluorescence corresponding to two singlet excited states. The high polarity of the lowest excited singlet states with charge-transfer nature is evidenced by the solvent shifts. Structural effects clearly demonstrate that Si-Si (and Si-Ge) bonds and aryl groups function as electron donors and acceptors, respectively. The excited-state dipole moment of PhSiMe2SiMe3 is found to be 4.3 D in good agreement with a calculated value of 3.8 D derived by an assumption of planar arrangement of the molecular frame, in which and x orbitals are orthogonal to each other, with full charge separation. The orthogonality of and x orbitals in the excited states is proved by the stereoelectronic effects on the fluorescence. The circumstance found for the present system is similar to twisted intramolecular charge-transfer (TICT) states of nx and sudden polarization in the excited singlet of xx systems, and orthogonal intramolecular charge transfer (OICT) is proposed as a general term.(1) Chemistry of Organosilicon Compounds 266. Based on the Plenary Lecture at the 8th International Symposium on Organosilicon Chemistry, St.

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ethanol-water: yield 3.42 g (first crop) (48.7%). 5,5'-Bis( 2-cyano-2-(ethoxycarbonyl)vinyl)-3,3',4,4'-tetramethyl-2,2'bipyrrole (56). 2-(2-Carbethoxy-2-cyanovinyl)-5-iodo-3,4-dimethyl-pyrrole2' (55) (3.44 g, 0.010 mol) was dissolved in N,N-dimethylformamide (20 mL) in a loosely stoppered Erlenmeyer flask. Copper bronze ( 5 g, BDH) was added at room temperature, and the stirred suspension was heated slowly. The original green color became orange-brown after the addition of the copper. As the solution was warmed, yellow solids (presumably the copper chelate of the iodopyrrole) crystallized out, making the copper bronze appear to clot. Iodine crystals (ca. 0.2 g) were added to activate the copper bronze. The mixture was then heated to, and just maintained at, the boiling point, with continued stirring, for 1 h.The yellow solids redissolved, and a permanent deep burgundy-red color set in as the reaction progressed. The mixture was allowed to cool somewhat, before being diluted with tetrahydrofuran (100 mL) and filtered to remove the excess copper. The solids were rinsed with tetrahydrofuran (300-400 mL) until the washings were nearly colorless and then with a solution of concentrated hydrochloric acid (20 mL) in THF (80 mL) and finally with water (400 mL), all of the washings and filtrates being collected together. The solids deposited from the aqueous solution were collected and rinsed with water. The bipyrrole is a striking purple color; in an especially finely divided form, the color is a pure Harvard crimson. If any bipyrrole appeared to remain in solution (a red color), it was recovered by further aqueous dilution. Addition of yet more water allowed the recovery of a modest quantity of the deiodinated monomer, 2-( 2-cyano-2-(ethoxycarbonyl)vinyl)-3,4-dimethylpyrr0le.~~The combined solids were boiled with dichloromethane (300-400 mL) in several portions and filtered hot, to remove gray cuprous iodide, which was rinsed until the filtrates were only pale orange. The solvent was displaced with ethanol at the boiling point and concentrated to approximately 50 mL, before being allowed to cool. The solids, most of which had crystallized during the concentration, were collected and rinsed with ethanol and then hexane. The yield of dark purple fluffy needles was 0.76 g (35%).An analytical sample was recrystallized from dichloromethane-95% ethanol: mp infusible below 300 OC. Anal. Calcd for C2,H2,N404: C, 66.34; H, 6.03; N, 12.90. Found: C, 65.90; H, 5.95; N, 12.75. IR (KBr) 3400, 2200, 1710, 1570 cm-'; MS, m / e 434; NMR (CF3C02H) 6 1.47 (t. J = 7 Hz, 6 H), 2.33 (s, 12 H), 4.50 (q, J = 7 Hz, 4 H), 8.26 (s, 2 H), 9.72 (s, 2 H).Preparation of a Zn(I1) Derivative of Decamethylaapphyrin (57). Decamethylsapphyrin (12) (55 mg, 0.10 mmol) in chloroform (80 mL) was heated to reflux for 1 h and then allowed to cool to room tempera-ture. A solution containing zinc acetate dihydrate (100 mg), anhydrous sodium acetate (120 mg), and methanol (3 mL) was added. The resulting solution was stirred at room temperature for 4 h and then al...

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