The interaction of rhodium(II) carboxylates with enzymes. (1/243)

The effect of rhodium(II) acetate, propionate, and methoxyacetate on the activity of 17 enzymes was evaluated. The enzymes were preincubated with the rhodium(II) complexes in order to detect irreversible inhibition. All enzymes that have essential sulfhydryl groups in or near their active site were found to be irreversibly inhibited. Those enzymes without essential sulfhydryl groups were not affected. In each case, the rate of inactivation closely paralleled the observed toxicity and antitumor activity of rhodium(II) carboxylates; that is, rhodium(II) propionate greater than rhodium(II) acetate greater than rhodium(II) methoxyacetate. In addition, those enzymes that have been demonstrated to be most sensitive to established sulfhydryl inhibitors, such as glyceraldehyde-3-phosphate dehydrogenase, were also most sensitive to rhodium(II) carboxylate inactivation. Proton nuclear magnetic resonance measurements made during the titration of rhodium(II) acetate with cysteine showed that breakdown of the carboxylate cage occurred as a result of reaction with this sulfhydryl-containing amino acid.  (+info)

Long-range oxidative damage to DNA: effects of distance and sequence. (2/243)

INTRODUCTION: Oxidative damage to DNA in vivo can lead to mutations and cancer. DNA damage and repair studies have not yet revealed whether permanent oxidative lesions are generated by charges migrating over long distances. Both photoexcited *Rh(III) and ground-state Ru(III) intercalators were previously shown to oxidize guanine bases from a remote site in oligonucleotide duplexes by DNA-mediated electron transfer. Here we examine much longer charge-transport distances and explore the sensitivity of the reaction to intervening sequences. RESULTS: Oxidative damage was examined in a series of DNA duplexes containing a pendant intercalating photooxidant. These studies revealed a shallow dependence on distance and no dependence on the phasing orientation of the oxidant relative to the site of damage, 5'-GG-3'. The intervening DNA sequence has a significant effect on the yield of guanine oxidation, however. Oxidation through multiple 5'-TA-3' steps is substantially diminished compared to through other base steps. We observed intraduplex guanine oxidation by tethered *Rh(III) and Ru(III) over a distance of 200 A. The distribution of oxidized guanine varied as a function of temperature between 5 and 35 degrees C, with an increase in the proportion of long-range damage (> 100 A) occurring at higher temperatures. CONCLUSIONS: Guanines are oxidized as a result of DNA-mediated charge transport over significant distances (e.g. 200 A). Although long-range charge transfer is dependent on distance, it appears to be modulated by intervening sequence and sequence-dependent dynamics. These discoveries hold important implications with respect to DNA damage in vivo.  (+info)

The effect of the antiscatter grid on full-field digital mammography phantom images. (3/243)

Computer Analysis of Mammography Phantom Images (CAMPI) is a method for making quantitative measurements of image quality. This article reports on a recent application of this method to a prototype full-field digital mammography (FFDM) machine. Images of a modified ACR phantom were acquired on the General Electric Diagnostic Molybdenum Rhodium (GE-DMR) FFDM machine at a number of x-ray techniques, both with and without the scatter reduction grid. The techniques were chosen so that one had sets of grid and non-grid images with matched doses (200 mrads) and matched gray-scale values (1500). A third set was acquired at constant 26 kVp and varying mAs for both grid conditions. Analyses of the images yielded signal-to-noise-ratio (SNR), contrast and noise corresponding to each target object, and a non-uniformity measure. The results showed that under conditions of equal gray-scale value the grid images were markedly superior, albeit at higher doses than the non-grid images. Under constant dose conditions, the non-grid images were slightly superior in SNR (7%) but markedly less uniform (60%). Overall, the grid images had substantially greater contrast and superior image uniformity. These conclusions applied to the whole kVp range studied for the Mo-Mo target filter combination and 4 cm of breast equivalent material of average composition. These results suggest that use of the non-grid technique in digital mammography with the GE-DMR-FFDM unit, is presently not warranted. With improved uniformity correction procedure, this conclusion would change and one should be able to realize a 14% reduction in patient dose at the same SNR by using a non-grid technique.  (+info)

Ca(2+)- and metabolism-related changes of mitochondrial potential in voltage-clamped CA1 pyramidal neurons in situ. (4/243)

In hippocampal slices from rats, dialysis with rhodamine-123 (Rh-123) and/or fura-2 via the patch electrode allowed monitoring of mitochondrial potential (DeltaPsi) changes and intracellular Ca(2+) ([Ca(2+)](i)) of CA1 pyramidal neurons. Plasmalemmal depolarization to 0 mV caused a mean [Ca(2+)](i) rise of 300 nM and increased Rh-123 fluorescence signal (RFS) by +info)

Robust charge transport in DNA double crossover assemblies. (5/243)

BACKGROUND: Multiple-stranded DNA assemblies, encoded by sequence, have been constructed in an effort to self-assemble nanodevices of defined molecular architecture. Double-helical DNA has been probed also as a molecular medium for charge transport. Conductivity studies suggest that DNA displays semiconductor properties, whereas biochemical studies have shown that oxidative damage to B-DNA at the 5'-G of a 5'-GG-3' doublet can occur by charge transport through DNA up to 20 nm from a photo-excited metallointercalator. The possible application of DNA assemblies, in particular double crossover (DX) molecules, in electrical nanodevices prompted the design of a DNA DX assembly with oxidatively sensitive guanine moieties and a tethered rhodium photo-oxidant strategically placed to probe charge transport. RESULTS: DX assemblies support long-range charge transport selectively down the base stack bearing the intercalated photo-oxidant. Despite tight packing, no electron transfer (ET) crossover to the adjacent base stack is observed. Moreover, the base stack of a DX assembly is well-coupled and less susceptible than duplex DNA to stacking perturbations. Introducing a double mismatch along the path for charge transport entirely disrupts long-range ET in duplex DNA, but only marginally decreases it in the analogous stack within DX molecules. CONCLUSIONS: The path for charge transport in a DX DNA assembly is determined directly by base stacking. As a result, the two closely packed stacks within this assembly are electronically insulated from one another. Therefore, DX DNA assemblies may serve as robust, insulated conduits for charge transport in nanoscale devices.  (+info)

Induction of chromosomal aberrations by the rhodium(III) complex cis-[Rh(biq)(2)Cl(2)]Cl in cultured human lymphocytes. (6/243)

The genotoxicity of the rhodium(III) complex cis-[Rh(biq)(2)Cl(2)]Cl (complex R) in cultured human lymphocytes was studied using the chromosome aberrations (CAs) assay. Lymphocyte cultures were initiated from two adult healthy non-smoking male volunteers and were exposed to the complex for a duration of 3 or 20 h prior to cell collection. The reduction in mitotic indices (MI) and the induction of CAs represented the toxic and clastogenic effects of the different treatments, respectively. Complex R proved to be an intermediate toxic clastogen with a MI(50) of 1.0 microg/ml and a minimum positive dose (MPD) of 0.1 microg/ml. Like bleomycin, complex R exerted its clastogenic effects without the need for metabolic activation and induced CAs of all types in lymphocytes treated in the G(2) and late S phases and, therefore, can be considered a radiomimetic. In addition, it induced more total CAs of chromatid-type than of chromosome-type. The reduction in the frequencies of CAs following the 20 h treatment as compared with those induced following the 3 h treatments indicated that human lymphocytes in the presence of complex R can partially tolerate the lesions involved in CA production. Based on the biological effects of complex R and the similarities between its functional group and that of bleomycin, possible mechanisms for complex R genotoxicity are discussed.  (+info)

Effects of cis-Dichlorudiammineplatinum (II) and related transition metal complexes on Escherichia Coli. (7/243)

A number of transition metal complexes, including the cis and trans isomers of dichlorodiammineplatinum (II), six complexes of rhodium (I), two of iridium (I), and one of ruthenium (II) have been tested for their ability to induce lambda prophage, to produce filamentous growth of Escherichia coli, and to be selectively toxic for strains with defects in the deoxyribonucleic acid repair system. Dichlorotetrakis(dimethylsulfoxide)ruthenium II [RuCl(2) (DMSO)(4)] was strictly similar to cis-dichlorodiammineplatinum II [cis PtCl(2) (NH(3))(2)] in the test for lambda induction, filamentous growth production, and selective toxicity for a recA(-) strain. [Rh COD 1,10-phenanthroline](+) Cl(-), though more toxic for recA(-) than for rec(+)E. coli, was scarcely effective in the test for filamentous growth and did not induce prophage. None of the other tested compounds showed any similarity with cis-PtCl(2)(NH(3))(2). Due to the interesting results obtained with cis-PtCl(2)(NH(3))(2) as an antitumor agent, it seems reasonable to propose RuCl(2)(DMSO)(4) as a potential antitumor substance.  (+info)

Charge transport through DNA four-way junctions. (8/243)

Long range oxidative damage as a result of charge transport is shown to occur through single crossover junctions assembled from four semi-complementary strands of DNA. When a rhodium complex is tethered to one of the arms of the four-way junction assembly, thereby restricting its intercalation into the pi-stack, photo-induced oxidative damage occurs to varying degrees at all guanine doublets in the assembly, though direct strand scission only occurs at the predicted site of intercalation. In studies where the Mg(2+) concentration was varied, so as to perturb base stacking at the junction, charge transport was found to be enhanced but not to be strongly localized to the arms that preferentially stack on each other. These data suggest that the conformations of four-way junctions can be relatively mobile. Certainly, in four-way junctions charge transport is less discriminate than in the more rigidly stacked DNA double crossover assemblies.  (+info)