The Experts below are selected from a list of 711 Experts worldwide ranked by ideXlab platform
Emerich S. Fiala - One of the best experts on this subject based on the ideXlab platform.
-
Comparison of Oxidative Damage to Rat Liver DNA and RNA by Primary Nitroalkanes, Secondary Nitroalkanes, Cyclopentanone Oxime, and Related Compounds1
2013Co-Authors: C. Clifford Conaway, Guo Nie, S. Hussain, Cancer Res, Contact The Aacr Publications, Emerich S. FialaAbstract:The hepatocarcinogen 2-Nitropropane causes oxidative damage to liver DNA and RNA after administration to rats; increases in 8-hydroxydeoxyguanosine and formation of an unknown moiety (DM) in DNA, plus increases in 8-hydroxyguanosine and the appearance of two unidentified peaks (KM and R\2) in RNA were observed by high-performance liquid chromatography of nucleosides from 2-Nitropropane-treated rats using electrochemical detection (E. S. Fiala et al.. Cancer Res., 49:5518-5522, 1989). In the present study, damage to Sprague-Dawley rat liver RNA and DNA was assessed to determine whether the characteristic pattern of oxidative nucleic acid damage caused by 2-Nitropropane also occurred after i.p. administration of primary nitroalkanes, other secondary nitroalkanes, 2-methyl-2-Nitropropane (a tertiary nitroalkane), and cyclopentanone oxime. All of the secondary nitroalkanes and cyclopentanone oxime significantly increased levels of 8-hydroxyguanine in both DNA and RN
-
analysis of nitrite nitrate in biological fluids denitrification of 2 Nitropropane in f344 rats
Analytical Biochemistry, 2000Co-Authors: Ock Soon Sohn, Emerich S. FialaAbstract:2-Nitropropane (2-NP), a rat hepatocarcinogen, is denitrified to nitrite and acetone by rat liver microsomes; the denitrification rate is increased using microsomes from phenobarbital (PB)-pretreated rats. To obtain evidence that denitrification of 2-NP also occurs in vivo, we attempted to determine nitrite and nitrate levels in blood sera and urines of 2-NP-treated (1.5 mmol/kg, ip, once) rats with and without PB pretreatment (80 mg/kg, ip, once daily, 3 days), using enzymatic reduction followed by the standard Griess reaction. However, due to various interfering factors, including pigment from methemoglobinemia, we found the assay had to be modified as follows: (a) reduction of nitrate to nitrite was accomplished using NADPH and nitrate reductase, (b) excess NADPH, proteins, and interfering pigments were precipitated using zinc acetate and Na(2)CO(3), and (c) the Griess reagents were prepared in 3 N HCl rather than 5% H(3)PO(4). With these modifications it became possible to show that 2-NP is indeed metabolized to nitrite in vivo and that the metabolism is increased by PB pretreatment. Two hours after 2-NP administration, rat blood serum nitrate plus nitrite levels were approximately 1600 microM (PB-pretreated) and 940 microM (vehicle-pretreated controls). The PB-pretreated and control rats, respectively, excreted 250 and 120 micromol nitrate/nitrite in the 24-h urine post 2-NP treatment. The modifications described make the method more specific, reproducible, and more widely applicable.
-
N2-amination of guanine to 2-hydrazinohypoxanthine, a novel in vivo nucleic acid modification produced by the hepatocarcinogen 2-Nitropropane.
Chemical Research in Toxicology, 1998Co-Authors: Rama S. Sodum, Emerich S. FialaAbstract:2-Nitropropane, an industrial chemical and a hepatocarcinogen in rats, induces aryl sulfotransferase-mediated liver DNA and RNA base modifications [Sodum, R. S., Sohn, O. S., Nie, G., and Fiala, E....
-
amination of tyrosine in liver cytosol protein of male f344 rats treated with 2 Nitropropane 2 nitrobutane 3 nitropentane or acetoxime
Chemical Research in Toxicology, 1997Co-Authors: Rama S. Sodum, Emerich S. FialaAbstract:Previously, the secondary nitroalkane 2-Nitropropane, a strong hepatocarcinogen in rats, had been shown to induce the formation of 8-aminoguanine in both DNA and RNA of rat liver through a sulfotransferase-mediated pathway. This pathway was postulated to convert the carcinogen into an aminating species [Sodum, R. S., et al. (1994) Chem. Res. Toxicol. 7, 344-351]. To submit this postulate to further test, we examined liver proteins of rats treated with 2-Nitropropane, other carcinogenic secondary nitroalkanes, or the related rat liver tumorigen acetoxime for the presence of 3-aminotyrosine, the expected product of tyrosine amination. Using ion-pair and/or cation-exchange high-performance liquid chromatography with electrochemical detection, we found that the liver cytosolic proteins of these animals contained 0.1-1.5 mol of 3-aminotyrosine/10(3) mol of tyrosine. Treatment with the noncarcinogenic primary nitroalkane 1-Nitropropane or with other primary nitroalkanes did not produce an analogous increase in the aminated amino acid (level of detection estimated at approximately 0.01 mol/10(3) mol of tyrosine). To our knowledge, this is the first report of the modification of protein tyrosine in vivo by a carcinogen. In vitro studies with acetoxime-O-sulfonate and hydroxylamine-O-sulfonate showed that these proposed intermediates in the activation pathway of 2-Nitropropane react with guanosine to give 8-aminoguanosine, N1-aminoguanosine, and 8-oxoguanosine and also react with tyrosine to give 3-aminotyrosine and 3-hydroxytyrosine. The in vitro amination and oxidation of guanosine at C8 were also produced by acetophenoxime-O-sulfonate and 2-heptanoxime-O-sulfonate. These results provide additional evidence for the production of a reactive species capable of aminating nucleic acids and proteins from 2-Nitropropane and other carcinogenic secondary nitroalkanes by a pathway involving oxime- and hydroxylamine-O-sulfonates as intermediates.
-
Inhibition of 2-Nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate
Carcinogenesis, 1997Co-Authors: Emerich S. Fiala, Ock Soon Sohn, Heyi Li, Karam El-bayoumy, Rama S. SodumAbstract:: We observed that pretreatment of male F344 rats with benzyl selenocyanate, a versatile organoselenium chemopreventive agent in several animal model systems, decreases the levels of DNA and RNA modifications produced in the liver by the hepatocarcinogen 2-Nitropropane. To clarify the mechanisms involved, we pretreated male F344 rats with either benzyl selenocyanate, its sulfur analog benzyl thiocyanate, phenobarbital or cobalt protoporphyrin IX; the latter is a depletor of P450. We then determined (1) the ability of liver microsomes to denitrify 2-Nitropropane, (2) effects on 2-Nitropropane-induced liver DNA and RNA modifications and (3) amount of nitrate excreted in rat urine following administration of the carcinogen. Pretreatment with benzyl selenocyanate or phenobarbital increased the denitrification activity of liver microsomes by 217 and 765%, respectively, increased liver P4502B1 by 31- and 435-fold, respectively, decreased the levels of 2-Nitropropane-induced modifications in liver DNA (29-70% and 17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and increased the 24-h urinary excretion of nitrate by 157 and 209%, respectively. Pretreatment with benzyl thiocyanate had no significant effect on any of these parameters. Pretreatment with cobalt protoporphyrin IX decreased liver P4502B 1 by 87%, decreased the denitrification activity of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate by 88.5%, but increased the extent of 2-Nitropropane-induced liver nucleic acid modifications by 17-67%. These results indicate that the metabolic sequence from 2-Nitropropane to the reactive species causing DNA and RNA modifications does not involve the removal of the nitro group. Moreover, they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic acid modifications in part by increasing its detoxication through induction of denitrification, although it is evident that other mechanisms must also be involved.
Laurie J Butler - One of the best experts on this subject based on the ideXlab platform.
-
Elucidating the Decomposition Mechanism of Energetic Materials with Geminal Dinitro Groups Using 2‑Bromo-2-Nitropropane Photodissociation
2016Co-Authors: Ryan S Booth, Chowshing Lam, Matthew D Brynteson, Lei Wang, Laurie J ButlerAbstract:These experiments photolytically generate two key intermediates in the decomposition mechanisms of energetic materials with nitro substituents, 2-nitropropene, and 2-nitro-2-propyl radicals. These intermediates are produced at high internal energies and access a number of competing unimolecular dissociation channels investigated herein. We use a combination of crossed laser-molecular beam scattering and velocity map imaging to study the photodissociation of 2-bromo-2-Nitropropane at 193 nm and the subsequent unimolecular dissociation of the intermediates above. Our results demonstrate that 2-bromo-2-Nitropropane has four primary photodissociation pathways: C–Br bond fission yielding the 2-nitro-2-propyl radical, HBr elimination yielding 2-nitropropene, C–N bond fission yielding the 2-bromo-2-propyl radical, and HONO elimination yielding 2-bromopropene. The photofragments are formed with significant internal energy and undergo many secondary dissociation events, including the exothermic dissociation of 2-nitro-2-propyl radicals to NO + acetone. Calculations at the G4//B3LYP/6-311++g(3df,2p) level show that the presence of a radical at a nitroalkyl center changes the mechanism for and substantially lowers the barrier to NO loss. This mechanism involves an intermediate with a three-center ring rather than the intermediate formed during the traditional nitro–nitrite isomerization. The observed dissociation pathways of the 2-nitro-2-propyl radical and 2-nitropropene help elucidate the decomposition mechanism of larger energetic materials with geminal dinitro groups
-
further studies into the photodissociation pathways of 2 bromo 2 Nitropropane and the dissociation channels of the 2 nitro 2 propyl radical intermediate
Journal of Physical Chemistry A, 2014Co-Authors: Ryan S Booth, Matthew D Brynteson, Shihhuang Lee, Jim J Lin, Laurie J ButlerAbstract:These experiments investigate the decomposition mechanisms of geminal dinitro energetic materials by photolytically generating two key intermediates: 2-nitropropene and 2-nitro-2-propyl radicals. To characterize the unimolecular dissociation of each intermediate, we form them under collision-free conditions using the photodissociation of 2-bromo-2-Nitropropane; the intermediates are formed at high internal energies and undergo a multitude of subsequent unimolecular dissociation events investigated herein. Complementing our prior work on this system, the new data obtained with a crossed-laser molecular beam scattering apparatus with VUV photoionization detection at Taiwan’s National Synchrotron Radiation Research Center (NSRRC) and new velocity map imaging data better characterize two of the four primary 193 nm photodissociation channels. The C–Br photofission channel forming the 2-nitro-2-propyl radicals has a trimodal recoil kinetic energy distribution, P(ET), suggesting that the 2-nitro-2-propyl radical...
-
Further Studies into the Photodissociation Pathways of 2‑Bromo-2-Nitropropane and the Dissociation Channels of the 2‑Nitro-2-propyl Radical Intermediate
2014Co-Authors: Ryan S Booth, Matthew D Brynteson, Shihhuang Lee, Jim J Lin, Laurie J ButlerAbstract:These experiments investigate the decomposition mechanisms of geminal dinitro energetic materials by photolytically generating two key intermediates: 2-nitropropene and 2-nitro-2-propyl radicals. To characterize the unimolecular dissociation of each intermediate, we form them under collision-free conditions using the photodissociation of 2-bromo-2-Nitropropane; the intermediates are formed at high internal energies and undergo a multitude of subsequent unimolecular dissociation events investigated herein. Complementing our prior work on this system, the new data obtained with a crossed-laser molecular beam scattering apparatus with VUV photoionization detection at Taiwan’s National Synchrotron Radiation Research Center (NSRRC) and new velocity map imaging data better characterize two of the four primary 193 nm photodissociation channels. The C–Br photofission channel forming the 2-nitro-2-propyl radicals has a trimodal recoil kinetic energy distribution, P(ET), suggesting that the 2-nitro-2-propyl radicals are formed both in the ground electronic state and in two low-lying excited electronic states. The new data also revise the HBr photoelimination P(ET) forming the 2-nitropropene intermediate. We then resolved the multiple competing unimolecular dissociation channels of each photoproduct, confirming many of the channels detected in the prior study, but not all. The new data detected HONO product at m/e = 47 using 11.3 eV photoionization from both intermediates; analysis of the momentum-matched products allows us to establish that both 2-nitro-2-propyl → HONO + CH3CCH2 and 2-nitropropene → HONO + C3H4 occur. Photoionization at 9.5 eV allowed us to detect the mass 71 coproduct formed in OH loss from 2-nitro-2-propyl; a channel missed in our prior study. The dynamics of the highly exothermic 2-nitro-2-propyl → NO + acetone dissociation is also better characterized; it evidences a sideways scattered angular distribution. The detection of some stable 2-nitropropene photoproducts allows us to fit signal previously assigned to H loss from 2-nitro-2-propyl radicals. Overall, the data provide a comprehensive study of the unimolecular dissociation channels of these important nitro-containing intermediates
-
elucidating the decomposition mechanism of energetic materials with geminal dinitro groups using 2 bromo 2 Nitropropane photodissociation
Journal of Physical Chemistry A, 2013Co-Authors: Ryan S Booth, Chowshing Lam, Matthew D Brynteson, Lei Wang, Laurie J ButlerAbstract:These experiments photolytically generate two key intermediates in the decomposition mechanisms of energetic materials with nitro substituents, 2-nitropropene, and 2-nitro-2-propyl radicals. These intermediates are produced at high internal energies and access a number of competing unimolecular dissociation channels investigated herein. We use a combination of crossed laser-molecular beam scattering and velocity map imaging to study the photodissociation of 2-bromo-2-Nitropropane at 193 nm and the subsequent unimolecular dissociation of the intermediates above. Our results demonstrate that 2-bromo-2-Nitropropane has four primary photodissociation pathways: C–Br bond fission yielding the 2-nitro-2-propyl radical, HBr elimination yielding 2-nitropropene, C–N bond fission yielding the 2-bromo-2-propyl radical, and HONO elimination yielding 2-bromopropene. The photofragments are formed with significant internal energy and undergo many secondary dissociation events, including the exothermic dissociation of 2-n...
Giovanni Gadda - One of the best experts on this subject based on the ideXlab platform.
-
inflated kinetic isotope effects in the branched mechanism of neurospora crassa 2 Nitropropane dioxygenase
Biochemistry, 2009Co-Authors: Kevin Francis, Giovanni GaddaAbstract:Catalytic turnover of Neurospora crassa 2-Nitropropane dioxygenase with nitroethane as substrate occurs through both nonoxidative and oxidative pathways. The pH dependence of the kinetic isotope effects with [1,1-2H2]nitroethane as substrate was measured in the current study by monitoring the formation of the nitronate product in the nonoxidative pathway. The kinetic isotope effect on the second-order rate constant for nitronate formation, kcat/Km, decreased from an upper limiting value of 23 ± 1 at low pH to a lower limiting value of 11 ± 1 at high pH. These kinetic isotope effects are three times larger than those determined previously through measurements of oxygen consumption that occurs in the oxidative pathway of the enzyme [(2006) Biochemistry 45, 13889]. Analytical expressions for the kcat/Km values determined in each study show that the difference in the kinetic isotope effects arises from the branching of an enzyme−ethylnitronate reaction intermediate through oxidative and nonoxidative turnover....
-
The nonoxidative conversion of nitroethane to ethylnitronate in Neurospora crassa 2-Nitropropane dioxygenase is catalyzed by histidine 196.
Biochemistry, 2008Co-Authors: Kevin Francis, Giovanni GaddaAbstract:The deprotonation of nitroethane catalyzed by Neurospora crassa 2-Nitropropane dioxygenase was investigated by measuring the formation and release of ethylnitronate formed in turnover as a function of pH and through mutagenesis studies. Progress curves for the enzymatic reaction obtained by following the increase in absorbance at 228 nm over time were visibly nonlinear, requiring a logarithmic approximation of the initial reaction rates for the determination of the kinetic parameters of the enzyme. The pH dependence of the second-order rate constant k cat/ K m with nitroethane as substrate implicates the presence of a group with a p K a of 8.1 +/- 0.1 that must be unprotonated for nitronate formation. Mutagenesis studies suggest that this group is histidine 196 as evident from the inability of a H196N variant form of the enzyme to catalyze the formation of ethylnitronate from nitroethane. Replacement of histidine 196 with asparagine resulted in an approximately 15-fold increase in the k cat/ K m with ethylnitronate as compared to the wild-type, which results from the inability of the mutant enzyme to undergo nonoxidative turnover. The results presented herein are consistent with a branched catalytic mechanism for the enzyme in which the ethylnitronate intermediate formed from the H196-catalyzed deprotonation of nitroethane partitions between release from the active site and oxidative denitrification to yield acetaldehyde and nitrite.
-
oxidation of alkyl nitronates catalyzed by 2 Nitropropane dioxygenase from hansenula mrakii
Archives of Biochemistry and Biophysics, 2008Co-Authors: Slavica Mijatovic, Giovanni GaddaAbstract:Abstract 2-Nitropropane dioxygenase from Hansenula mrakii was expressed in Escherichia coli cells and purified in active and stable form using 60% saturation of ammonium sulfate and a single chromatographic step onto a DEAE column. MALDI-TOF mass spectrometric and spectrophotometric analyses of the flavin extracted by heat or acid denaturation of the enzyme indicated that FMN, and not FAD as erroneously reported previously, is present in a 1:1 stoichiometry with the protein. Inductively coupled plasma mass spectrometric analysis of the enzyme established that H. mrakii 2-Nitropropane dioxygenase contains negligible amounts of iron, manganese, zinc, and copper ions, which are not catalytically relevant. Anaerobic substrate reduction and kinetic data using a Clark oxygen electrode to measure rates of oxygen consumption indicated that the enzyme is active on a broad range of alkyl nitronates, with a marked preference for unbranched substrates over propyl-2-nitronate. Interestingly, the enzyme reacts poorly, if at all, with nitroalkanes, as suggested by lack of both anaerobic reduction of the enzyme-bound flavin and consumption of oxygen with nitroethane, nitrobutane, and 2-Nitropropane. Finally, both the tight binding of sulfite ( K d = 90 μM, at pH 8 and 15 °C) to the enzyme and the formation of the anionic flavosemiquinone upon anaerobic incubation with alkyl nitronates are consistent with the presence of a positively charged group in proximity of the N(1) C(2) O atoms of the FMN cofactor.
-
Probing the Chemical Steps of Nitroalkane Oxidation Catalyzed by 2-Nitropropane Dioxygenase with Solvent Viscosity, pH, and Substrate Kinetic Isotope Effects†
Biochemistry, 2006Co-Authors: Kevin Francis, Giovanni GaddaAbstract:Among the enzymes that catalyze the oxidative denitrification of nitroalkanes to carbonyl compounds, 2-Nitropropane dioxygenase is the only one known to effectively utilize both the neutral and anionic (nitronate) forms of the substrate. A recent study has established that the catalytic pathway is common to both types of substrates, except for the initial removal of a proton from the α carbon of the neutral substrates [Francis, K., Russell, B., and Gadda, G. (2005) J. Biol. Chem. 280, 5195−5204]. In the present study, the mechanistic properties of the enzyme have been investigated with solvent viscosity, pH, and kinetic isotope effects. With nitroethane or ethylnitronate, the kcat/Km and kcat values were independent of solvent viscosity, consistent with the substrate and product binding to the enzyme in rapid equilibrium. The abstraction of the proton from the α carbon of neutral substrates was investigated by measuring the pH dependence of the D(kcat/KNE) value with 1,1-[2H2]-nitroethane. The formation o...
-
Involvement of a flavosemiquinone in the enzymatic oxidation of nitroalkanes catalyzed by 2-Nitropropane dioxygenase.
The Journal of biological chemistry, 2004Co-Authors: Kevin Francis, Bethany Russell, Giovanni GaddaAbstract:Abstract 2-Nitropropane dioxygenase (EC 1.13.11.32) catalyzes the oxidation of nitroalkanes into their corresponding carbonyl compounds and nitrite. In this study, the ncd-2 gene encoding for the enzyme in Neurospora crassa was cloned, expressed in Escherichia coli, and the resulting enzyme was purified. Size exclusion chromatography, heat denaturation, and mass spectroscopic analyses showed that 2-Nitropropane dioxygenase is a homodimer of 80 kDa, containing a mole of non-covalently bound FMN per mole of subunit, and is devoid of iron. With neutral nitroalkanes and anionic nitronates other than propyl-1- and propyl-2-nitronate, for which a non-enzymatic free radical reaction involving superoxide was established using superoxide dismutase, substrate oxidation occurs within the enzyme active site. The enzyme was more specific for nitronates than nitroalkanes, as suggested by the second order rate constant kcat/Km determined with 2-Nitropropane and primary nitroalkanes with alkyl chain lengths between 2 and 6 carbons. The steady state kinetic mechanism with 2-Nitropropane, nitroethane, nitrobutane, and nitrohexane, in either the neutral or anionic form, was determined to be sequential, consistent with oxygen reacting with a reduced form of enzyme before release of the carbonyl product. Enzyme-monitored turnover with ethyl nitronate as substrate indicated that the catalytically relevant reduced form of enzyme is an anionic flavin semiquinone, whose formation requires the substrate, but not molecular oxygen, as suggested by anaerobic substrate reduction with nitroethane or ethyl nitronate. Substrate deuterium kinetic isotope effects with 1,2-[2H4]nitroethane and 1,1,2-[2H3 ethyl nitronate at pH 8 yielded normal and inverse effects on the kcat/Km value, respectively, and were negligible on the kcat value. The kcat/Km and kcat pH profiles with anionic nitronates showed the requirement of an acid, whereas those for neutral nitroalkanes were consistent with the involvement of both an acid and a base in catalysis. The kinetic data reported herein are consistent with an oxidasestyle catalytic mechanism for 2-Nitropropane dioxygenase, in which the flavin-mediated oxidation of the anionic nitronates or neutral nitroalkanes and the subsequent oxidation of the enzyme-bound flavin occur in two independent steps.
Richard G. Compton - One of the best experts on this subject based on the ideXlab platform.
-
a theoretical and experimental approach to the adiabaticity of diffusional electron transfer processes electroreduction of 2 Nitropropane on mercury microelectroelectrodes
Journal of Electroanalytical Chemistry, 2013Co-Authors: Eduardo Laborda, Danu Suwatchara, Christopher Batchelormcauley, Richard G. ComptonAbstract:Abstract A theoretical and experimental approach to the degree of adiabaticity of electrode processes is considered for the case where the electroactive species of the redox couple move freely in solution. Within a transition state-like framework, the adiabatic effect on the activation energy of electron transfer is included through the theory developed by Schmickler (W. Schmickler, J. Electroanal. Chem. 204 (1986) 31). The effect on the probability of electron tunnelling is also incorporated according to the Landau–Zener formalism (L. Landau, Phys. Z. Sowjetunion, 1932 [29] ; C. Zener, Proc. R. Soc. London A 140 (1933) 660). In applying both aspects, it is recognised that the electron transfer takes place over a range of distances from the electrode surface. The theory is applied to the study of the electroreduction kinetics of 2-Nitropropane in fully-supported DMSO solutions on mercury hemispherical microelectrodes of 23 μm radius. By fitting of experimental cyclic voltammetry, the standard rate constant (k0) is determined at different temperatures and for different supporting electrolytes. The reorganization energy and degree of adiabaticity from the variation of k0 with temperature are evaluated.
-
giving physical insight into the butler volmer model of electrode kinetics application of asymmetric marcus hush theory to the study of the electroreductions of 2 methyl 2 Nitropropane cyclooctatetraene and europium iii on mercury microelectrodes
Journal of Electroanalytical Chemistry, 2012Co-Authors: Martin C Henstridge, Neil V. Rees, Francisco Martinezortiz, Danu Suwatchara, Richard G. ComptonAbstract:Abstract The asymmetric Marcus–Hush (MH) model for electrode kinetics is applied to the kinetic study of the electroreduction of 2-methyl-2-Nitropropane in acetonitrile, cyclooctatetraene in dimethylsulfoxide and europium(III) in aqueous solution, using mercury microhemispheres as working electrodes. This kinetic model includes the possibility of the oxidative and reductive processes having different reorganization energies due to differences between the force constants of the electroactive species. For each redox couple, the response obtained in cyclic and square wave voltammetries can be fitted satisfactorily with the four-parameter asymmetric MH model. From the fitting of the voltammograms the values of the kinetic parameters are extracted and analyzed in terms of physical properties of the electroactive species. A comparison of the asymmetric model against the simpler, phenomenological Butler–Volmer (BV) approach is discussed, as well as a possible physical interpretation for the BV transfer coefficient.
-
Quantitative weaknesses of the Marcus-Hush theory of electrode kinetics revealed by Reverse Scan Square Wave Voltammetry: The reduction of 2-methyl-2-Nitropropane at mercury microelectrodes
Chemical Physics Letters, 2011Co-Authors: Eduardo Laborda, Angela Molina, Martin C Henstridge, Yijun Wang, Francisco Martínez-ortiz, Richard G. ComptonAbstract:Abstract The Marcus-Hush and Butler–Volmer kinetic electrode models are compared experimentally by studying the reduction of 2-methyl-2-Nitropropane in acetonitrile at mercury microelectrodes using Reverse Scan Square Wave Voltammetry. This technique is found to be very sensitive to the electrode kinetics and to permit critical comparison of the two models. The Butler–Volmer model satisfactorily fits the experimental data whereas Marcus-Hush does not quantitatively describe this redox system.
Rama S. Sodum - One of the best experts on this subject based on the ideXlab platform.
-
N2-amination of guanine to 2-hydrazinohypoxanthine, a novel in vivo nucleic acid modification produced by the hepatocarcinogen 2-Nitropropane.
Chemical Research in Toxicology, 1998Co-Authors: Rama S. Sodum, Emerich S. FialaAbstract:2-Nitropropane, an industrial chemical and a hepatocarcinogen in rats, induces aryl sulfotransferase-mediated liver DNA and RNA base modifications [Sodum, R. S., Sohn, O. S., Nie, G., and Fiala, E....
-
amination of tyrosine in liver cytosol protein of male f344 rats treated with 2 Nitropropane 2 nitrobutane 3 nitropentane or acetoxime
Chemical Research in Toxicology, 1997Co-Authors: Rama S. Sodum, Emerich S. FialaAbstract:Previously, the secondary nitroalkane 2-Nitropropane, a strong hepatocarcinogen in rats, had been shown to induce the formation of 8-aminoguanine in both DNA and RNA of rat liver through a sulfotransferase-mediated pathway. This pathway was postulated to convert the carcinogen into an aminating species [Sodum, R. S., et al. (1994) Chem. Res. Toxicol. 7, 344-351]. To submit this postulate to further test, we examined liver proteins of rats treated with 2-Nitropropane, other carcinogenic secondary nitroalkanes, or the related rat liver tumorigen acetoxime for the presence of 3-aminotyrosine, the expected product of tyrosine amination. Using ion-pair and/or cation-exchange high-performance liquid chromatography with electrochemical detection, we found that the liver cytosolic proteins of these animals contained 0.1-1.5 mol of 3-aminotyrosine/10(3) mol of tyrosine. Treatment with the noncarcinogenic primary nitroalkane 1-Nitropropane or with other primary nitroalkanes did not produce an analogous increase in the aminated amino acid (level of detection estimated at approximately 0.01 mol/10(3) mol of tyrosine). To our knowledge, this is the first report of the modification of protein tyrosine in vivo by a carcinogen. In vitro studies with acetoxime-O-sulfonate and hydroxylamine-O-sulfonate showed that these proposed intermediates in the activation pathway of 2-Nitropropane react with guanosine to give 8-aminoguanosine, N1-aminoguanosine, and 8-oxoguanosine and also react with tyrosine to give 3-aminotyrosine and 3-hydroxytyrosine. The in vitro amination and oxidation of guanosine at C8 were also produced by acetophenoxime-O-sulfonate and 2-heptanoxime-O-sulfonate. These results provide additional evidence for the production of a reactive species capable of aminating nucleic acids and proteins from 2-Nitropropane and other carcinogenic secondary nitroalkanes by a pathway involving oxime- and hydroxylamine-O-sulfonates as intermediates.
-
Inhibition of 2-Nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate
Carcinogenesis, 1997Co-Authors: Emerich S. Fiala, Ock Soon Sohn, Heyi Li, Karam El-bayoumy, Rama S. SodumAbstract:: We observed that pretreatment of male F344 rats with benzyl selenocyanate, a versatile organoselenium chemopreventive agent in several animal model systems, decreases the levels of DNA and RNA modifications produced in the liver by the hepatocarcinogen 2-Nitropropane. To clarify the mechanisms involved, we pretreated male F344 rats with either benzyl selenocyanate, its sulfur analog benzyl thiocyanate, phenobarbital or cobalt protoporphyrin IX; the latter is a depletor of P450. We then determined (1) the ability of liver microsomes to denitrify 2-Nitropropane, (2) effects on 2-Nitropropane-induced liver DNA and RNA modifications and (3) amount of nitrate excreted in rat urine following administration of the carcinogen. Pretreatment with benzyl selenocyanate or phenobarbital increased the denitrification activity of liver microsomes by 217 and 765%, respectively, increased liver P4502B1 by 31- and 435-fold, respectively, decreased the levels of 2-Nitropropane-induced modifications in liver DNA (29-70% and 17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and increased the 24-h urinary excretion of nitrate by 157 and 209%, respectively. Pretreatment with benzyl thiocyanate had no significant effect on any of these parameters. Pretreatment with cobalt protoporphyrin IX decreased liver P4502B 1 by 87%, decreased the denitrification activity of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate by 88.5%, but increased the extent of 2-Nitropropane-induced liver nucleic acid modifications by 17-67%. These results indicate that the metabolic sequence from 2-Nitropropane to the reactive species causing DNA and RNA modifications does not involve the removal of the nitro group. Moreover, they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic acid modifications in part by increasing its detoxication through induction of denitrification, although it is evident that other mechanisms must also be involved.
-
Activation of the liver carcinogen 2-Nitropropane by aryl sulfotransferase.
Chemical Research in Toxicology, 1994Co-Authors: Rama S. Sodum, Ock Soon Sohn, Guo Nie, Emerich S. FialaAbstract:8-Aminoguanine had previously been identified as one of the nucleic acid base modifications produced in livers of rats by treatment with the hepatocarcinogen 2-Nitropropane (2-NP), and a hypothetical mechanism of activation of 2-NP to hydroxylamine-O-sulfonate or acetate that would lead to NH2+, an aminating species, was proposed [Sodum et al. (1993) Chem. Res. Toxicol. 6, 269-276]. We now present in vivo and in vitro experimental evidence for the activation of 2-NP to an aminating species by rat liver aryl sulfotransferase. Pretreatment of rats with the aryl sulfotransferase inhibitors pentachlorophenol or 2,6-dichloro-4-nitrophenol significantly decreased the levels of liver nucleic acid modifications produced by 2-NP treatment. Furthermore, partially purified rat liver aryl sulfotransferase was shown to activate 2-NP and 2-NP nitronate in vitro at neutral pH and 37 degrees C, to a reactive species that aminated guanosine at the C8 position. This activation was dependent on the presence of the enzyme, its specific cofactor adenosine 3'-phosphate 5'-phosphosulfate, and mercaptoethanol. As in the case of the in vitro studies, pentachlorophenol and 2,6-dichloro-4-nitrophenol inhibited the in vitro formation of 8-aminoguanosine and 8-oxoguanosine. The corresponding primary nitroalkane, 1-Nitropropane, which is not mutagenic and does not appear to be carcinogenic, was not a substrate for aryl sulfotransferase in the in vitro amination of guanosine.
-
2 Nitropropane induced liver dna and rna base modifications differences between sprague dawley rats and new zealand white rabbits
Cancer Letters, 1993Co-Authors: Emerich S. Fiala, Rama S. Sodum, Clifford C Conaway, Guo Nie, Ock Soon SohnAbstract:2-Nitropropane (2-NP), a hepatocarcinogen in male Sprague-Dawley rats but not, under the same conditions, in male New Zealand White rabbits, induces characteristic base modifications in rat liver DNA and RNA including increases in 8-oxoguanine and the formation of 8-aminoguanine. We compared the levels of these modifications in the two animal species at 6, 18 and 42 h after a single i.p. treatment with 1.12 mmol/kg 2-NP. Significantly less nucleic acid base modifications were found to be produced in rabbit liver than in rat liver. Thus, the relative resistance of the rabbit to the hepatocarcinogenicity of 2-NP correlates with decreased levels of 2-NP-induced liver DNA and RNA base damage.
