Oxidation and Radical Intermediates Associated with the Glutathione Conjugation of Mucochloric Acid

LaLonde, Robert T.; Xie, Shan; Chamulitrat, Waleé; Mason, Ronald P.

doi:10.1021/tx00040a002

Cited by 11 publications

(5 citation statements)

References 23 publications

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“…The current work, the previous work in our laboratory on identification of the "etheno" and "ethenocarbaldehyde" derivatives of nucleosides, and the work of LaLonde et al concerning MCA-GSH conjugates and the generation of reactive MCA radicals show that MCA may react with biomolecules along several diverse pathways (12)(13)(14)(15). Additional pathways will be discovered when the still unidentified peaks in our HPLC chromatograms of MCA-nucleosides reaction mixtures are identified.…”

Section: Resultsmentioning

confidence: 52%

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Reaction of Mucochloric Acid with Adenosine: Formation of 8-(N6-Adenosinyl)ethenoadenosine Derivatives

Asplund¹,

Kronberg²,

Sjöholm³

et al. 1995

Chem. Res. Toxicol.

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The bacterial mutagen mucochloric acid was reacted with adenosine in aqueous solutions at 37 degrees C. In the HPLC chromatograms of the reaction mixtures two peaks of unidentified products were observed at longer retention times than the previously characterized "etheno" and "ethenocarbaldehyde" adducts. Following isolation and purification with chromatographic methods, the products were characterized by UV absorbance, 1H and 13C NMR spectroscopy, and thermospray mass spectrometry. The products were found to consist of ethenoadenosine derivatives which bonded an additional adenosine unit to C-8 in the etheno bridge. In one of the products a formyl group and in the other an oxalo group was localized at C-7 in the etheno bridge. The yield of the products was about 0.04 mol% (calculated from the original amount of adenosine) in the reaction mixture held for 4 days at pH 7.4. It was concluded that mucochloric acid acts as an oxidative agent during the course of formation of the products.

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Section: Resultsmentioning

confidence: 52%

“…LaLonde et al have shown that MCA reacts with GSH and forms stable GSH-MCA conjugates (14). Very recently, LaLonde et al observed that MCA may also oxidize GSH to GSSG and in this way cause an inactivation of GSH in cellular systems (15).…”

Section: Introduction Chart Iomentioning

confidence: 99%

Reaction of Mucochloric Acid with Adenosine: Formation of 8-(N6-Adenosinyl)ethenoadenosine Derivatives

Asplund¹,

Kronberg²,

Sjöholm³

et al. 1995

Chem. Res. Toxicol.

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“…How might such a radical anion be generated, and how might it be involved in chemical processes manifested ultimately as mutagenesis? Recently, MCA radical anion (MCA1-) was observed as an intermediate when MCA was treated with GSH (16). The stable reaction products were the GSH-MCA conjugates and GSSG.…”

Section: Results Analysis and Discussionmentioning

confidence: 99%

Interactive Chlorine-by-Bromine and Hydrogen-by-Hydroxyl Group Replacement Effects in 2(5H)-Furanone Mutagenicity

LaLonde¹,

Leo²

1994

Chem. Res. Toxicol.

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Both bromine- and chlorine-substituted 2(5H)-furanones are produced by the chlorination of ligno-humic waters containing bromide ion. The molar mutagenicities of four bromine- and chlorine-substituted 2(5H)-furanones were determined by the Salmonella typhimurium (TA100) assay to explore Cl-by-Br and H-by-OH replacement effects on mutagenicity. Each of these two replacements was expected to enhance mutagenicity based on earlier work showing that lower LUMO energy levels and greater radical anion stability correlated with elevated TA100 mutagenicity. The four compounds investigated were the following: 2,3-dibromo-5-hydroxy-2(5H)-furanone (mucobromic acid, MBA); 2,3-dibromo-2(5H)-furanone (reduced mucobraomic acid, RMBA); 2,3-dichloro-5-hydroxy-2(5H)-furanone (mucochloric acid, MCA); and 2,3-dichloro-2(5H)-furanone (reduced mucochloric acid, RMCA). Mean molar mutagenicities were found to be 5.54, 1.18, 2.92 and 0.105 revertants/nmol for the four compounds in the order named. Mutagenicity enhancements resulting from Cl-by-Br and H-by-OH replacements were analyzed by simple ratios of mean molar mutagenicity and by multiple regression analysis. The effect of the Cl-by-Br replacement on mutagenicity amounted to a 1.9-fold enhancement in the presence of C-5 OH, but an 11-fold enhancement in the presence of C-5 H. This demonstrated that the two replacement effects were interactive. Higher mutagenicity values corresponded to lower AM1 computed LUMO energy levels and greater radical anion stabilities.

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“…This unusual high mutagenicity attracted considerable attention from many researchers. [6][7][8][9][10] Until recently, MX was assumed to pose little carcinogenic risk due to its low exposure, high reactivity and short residence time. 11 But recent identification of DNA adducts 12,13 and evidence of carcinogenicity along the gastro-intestinal lining in rodents following MX exposure has heightened concern for this class of chemicals.…”

Section: Introductionmentioning

confidence: 99%

Hologram Quantitative Structure Activity Relationship (HQSAR) Study of Mutagen X

2005

Bulletin of the Korean Chemical Society

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MX and its analogs are synthesized and modeled by quantitative structure activity relationship (QSAR) study including comparative molecular field analysis (CoMFA). As a result, factors affecting this class of compounds have been found to be steric and electrostatic effects. Because hologram quantitative structure activity relationship (HQSAR) technique is based on the 2-dimensional descriptors, this is free of ambiguity of conformational selection and molecular alignment. In this study we tried to include all the data available from the literature, and modeled with the HQSAR technique. Among the parameters affecting fragmentation, connectivity was the most important one for the whole compounds, giving good statistics. Considering additional parameters such as bond specification only slightly improved the model. Therefore connectivity has been found to be the most appropriate to explain the mutagenicity for this class of compounds.

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Oxidation and Radical Intermediates Associated with the Glutathione Conjugation of Mucochloric Acid

Cited by 11 publications

References 23 publications

Reaction of Mucochloric Acid with Adenosine: Formation of 8-(N6-Adenosinyl)ethenoadenosine Derivatives

Reaction of Mucochloric Acid with Adenosine: Formation of 8-(N6-Adenosinyl)ethenoadenosine Derivatives

Interactive Chlorine-by-Bromine and Hydrogen-by-Hydroxyl Group Replacement Effects in 2(5H)-Furanone Mutagenicity

Hologram Quantitative Structure Activity Relationship (HQSAR) Study of Mutagen X

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