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Enhancement by cysteinyl thiols of acetyltransferase-mediated, but not of sulfotransferase-mediated, binding of a pyrolysate-derived N-hydroxyarylamine, 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole, to DNA. 1990

M Abu-Zeid, and N Staiano, and Y Yamazoe, and R Kato
Department of Pharmacology, School of Medicine, Keio University, Tokyo.

The effect of thiols on the activation of a pyrolysate-derived N-hydroxyarylamine, 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P-1), was studied in vitro. In hepatic cytosol of rats, [3H]-N-hydroxy-Glu-P-1 bound covalently to calf thymus DNA in the presence of acetyl CoA or 3'-phosphoadenosine-5'-phosphosulfate (PAPS). The extent of the binding of N-hydroxy-Glu-P-1 in a PAPS-dependent system was decreased by the addition of 10 mM glutathione, N-acetyl-L-cysteine, 2-mercaptoethanol or dithiothreitol. However, acetyl CoA-dependent binding of N-hydroxy-Glu-P-1 was stimulated by the addition of 10 mM N-acetyl-L-cysteine (3 fold), L-cysteine (2 fold) or glutathione (1.2 fold), but not 10 mM 2-mercaptoethanol or L-methionine. After hydrolysis of the modified DNA, no difference was detected in the physicochemical properties of the nucleoside adduct formed in the acetyl CoA-supported system with and without thiols. These results indicate that thiols with a cysteine residue are able to affect the activation of carcinogenic heterocyclic arylamines selectively by the modulation of the acetyltransferase-mediated, but not the sulfotransferase-mediated, pathway.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008623 Mercaptoethanol A water-soluble thiol derived from hydrogen sulfide and ethanol. It is used as a reducing agent for disulfide bonds and to protect sulfhydryl groups from oxidation. 2-ME,2-Mercaptoethanol,2 Mercaptoethanol
D008715 Methionine A sulfur-containing essential L-amino acid that is important in many body functions. L-Methionine,Liquimeth,Methionine, L-Isomer,Pedameth,L-Isomer Methionine,Methionine, L Isomer
D010724 Phosphoadenosine Phosphosulfate 3'-Phosphoadenosine-5'-phosphosulfate. Key intermediate in the formation by living cells of sulfate esters of phenols, alcohols, steroids, sulfated polysaccharides, and simple esters, such as choline sulfate. It is formed from sulfate ion and ATP in a two-step process. This compound also is an important step in the process of sulfur fixation in plants and microorganisms. Adenosine-3'-phosphate-5'-Phosphosulfate,Adenosine 3' phosphate 5' Phosphosulfate,Phosphosulfate, Phosphoadenosine
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D003545 Cysteine A thiol-containing non-essential amino acid that is oxidized to form CYSTINE. Cysteine Hydrochloride,Half-Cystine,L-Cysteine,Zinc Cysteinate,Half Cystine,L Cysteine
D003600 Cytosol Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components. Cytosols
D004229 Dithiothreitol A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols. Cleland Reagent,Cleland's Reagent,Sputolysin,Clelands Reagent,Reagent, Cleland,Reagent, Cleland's
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA

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