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Showing papers in "Chemico-Biological Interactions in 1998"


Journal ArticleDOI
TL;DR: Treatment with an inhibitor, buthionine sulfoximine (BSO), of gamma-glutamylcysteine synthetase leads to decreased cellular GSH levels, and its application can provide a useful experimental model of GSH deficiency.

880 citations


Journal ArticleDOI
TL;DR: The glyoxalase system is a metabolic pathway that catalyses the detoxification of alpha-oxoaldehydes RCOCHO to corresponding aldonic acids RCH(OH)CO2H, and protects cells from alpha-Oxoaldehyde-mediated formation of advanced glycation endproducts (AGEs).

306 citations


Journal ArticleDOI
TL;DR: This review summarises current knowledge of the sulfation system and the enzymes involved, and illustrates how heterologous expression of sulfotransferases (SULTs) and sulfatases is aiding the authors' appreciation of the properties of these important proteins.

201 citations


Journal ArticleDOI
TL;DR: Consistent and profound GSH depletion was observed in serial determinations of tumor GSH levels in patients receiving continuous infusion (CI) BSO, and evidence of clinical activity has been observed in patients with alkylating or platinating agent-refractory tumors.

159 citations


Journal ArticleDOI
TL;DR: The most potent compound, FICZ, is a good candidate for the endogenous ligand of the Ah receptor necessary for normal development and for the basal expression of Ah receptor-dependent genes.

153 citations


Journal ArticleDOI
TL;DR: Novel 1H-cyclopenta[b]benzofuran lignans are potent cytostatic inhibitors of protein biosynthesis and are capable of delaying tumor growth in an in vivo model and their full clinical or basic utility requires further investigation.

129 citations


Journal ArticleDOI
TL;DR: The effects on enzyme activities in vitro suggest that there is not only the potential for flavonoids to alter metabolic activation of carcinogens but also of therapeutically administered drugs in vivo.

128 citations


Journal ArticleDOI
TL;DR: The membrane proteins mediating the ATP-dependent transport of glutathione S-conjugates and related amphiphilic anions have been identified as the multidrug resistance proteins MRP1 and MRP2, associated with multiple drug resistance of malignant tumors because of their capacity to pump drug conjugates and drug complexes across the plasma membrane into the extracellular space.

124 citations


Journal ArticleDOI
Colin J. Henderson1, Aileen W. McLaren1, G J Moffat1, E J Bacon1, C R Wolf1 
TL;DR: In an attempt to elucidate the endogenous role(s) of GST pi, the laboratory has used homologous recombination in embryonic stem (ES) cells to inactivate both murine GST Pi genes and create a mouse strain completely deficient in the expression of this enzyme.

124 citations


Journal ArticleDOI
TL;DR: This chapter concludes with a discussion of strategies for using GGT to activate and target chemotherapy drugs to tumors as a means of improving treatment for common human malignancies.

120 citations


Journal ArticleDOI
TL;DR: From the pH-dependence of the peak current it is possible to affirm that pH 2 is the better condition for the oxidative activity of gallate radicals showing that the antioxidant behaviour of these compounds are important in the stomach acid.

Journal ArticleDOI
TL;DR: Metallothioneins is a stress-inducible protein with antioxidant attributes that may participate independently or in conjunction with GSH to protect cells against injurious agents.

Journal ArticleDOI
TL;DR: This chapter describes the abundant preclinical data that support the development of pharmacologic strategies to lower GSH and inactivate the gluathione-S-transferases to make anti-cancer drugs more effective.

Journal ArticleDOI
TL;DR: A class of disulfide inhibitors of thioredoxin has been identified that inhibit cancer cell growth in culture and have antitumor activity against some human tumor xenografts in animals.

Journal ArticleDOI
TL;DR: A review of Medline and CancerLit databases indicated that interest in I3C, as a cancer chemopreventive agent, has increased significantly in the past 5-10 years, but few studies provide clear evidence for promotion or enhancement of carcinogenesis.

Journal ArticleDOI
TL;DR: Molecular cloning and heterologous expression of rat GSTA5-5 has led to the demonstration that it exhibits substantially greater activity for AFB1-8,9-epoxide than other rat transferases, and a novel aflatoxin-aldehyde reductase (AFAR) that is similarly induced by ethoxyquin is identified.

Journal ArticleDOI
TL;DR: Results suggest that regulation of p-nitrophenol sulfation occurs at the level of gene transcription of ST1A3 which is the major transcript of the three PSULT mRNAs and that a polygenic basis for the apparent genetic polymorphism of sulfation was likely because of the existence of ST 1A3 variants.

Journal ArticleDOI
TL;DR: The results showed that bismuth was not toxic even at the highest dose used, while zinc, cadmium and mercury exhibited varying degrees of toxicity, zinc being the least toxic and mercury the most potent.

Journal ArticleDOI
TL;DR: It is demonstrated that binding energy components are primarily hydrophobic/desolvation and electrostatic/hydrogen-bonded in nature, whereas electronic factors are of importance in determining variations in reaction rates.

Journal ArticleDOI
TL;DR: Butyric acid inhibition of bacterial growth may explain in part, the role of pre-intestinal lipases in young animals' natural defenses against bacteria in ingested food prior to weaning.

Journal ArticleDOI
TL;DR: It still remains unclear however, why particular glutathione S-transferase loci are associated with altered risk in some diseases but not others, and the true in vivo substrates of these enzymes is unknown, consequently their mechanism of action remains unclear.

Journal ArticleDOI
TL;DR: It is indicated that C60, on photosensitization, can induce significant lipid peroxidation and other forms of oxidative damage in biological membranes and that this phenomenon can be greatly modulated by endogenous antioxidants and scavengers of reactive oxygen species.

Journal ArticleDOI
TL;DR: The results indicate that OH-PCBs are potent inhibitors of this activity in vitro, with IC50 concentrations in the low micro molar range, and T2 can be used as the model substrate for the active hormone T3.

Journal ArticleDOI
TL;DR: The use of cultured normal and SV40T antigen-immortalized human buccal epithelial cells are used as model systems for aldehyde exposure of the oral epithelium, occurring through the ingestion of alcoholic beverages and brewed coffee, as well as by inhalation of tobacco smoke and automobile exhaust.

Journal ArticleDOI
TL;DR: Rat and human sulfotransferases have been stably expressed in his- Salmonella typhimurium strain TA1538 and Chinese hamster V79 cells and site-dependent expression together with the limitations in the distribution of reactive sulfuric acid conjugates may explain organotropic effects of compounds activated by this metabolic pathway.

Journal ArticleDOI
TL;DR: This series of studies was designed to analyze SULT mRNA expression and hormonal regulation in male and female rats and found that Estrogen sulfotransferase (SULT1E2) may play a role in estrogen homeostasis.

Journal ArticleDOI
TL;DR: The preliminary characterization of iodothyronine sulfotransferase activities of rat and human liver cytosol and recombinant rSult1C1 and hSULT1A1 isoenzymes suggest that rSULT 1C1 is an important isoenzyme for the sulfation of thyroid hormone in male rat liver and another isoen enzyme with similar properties, perhaps rSault1B1, is responsible for thyroid hormone sulfation in female rat liver.

Journal ArticleDOI
TL;DR: It was demonstrated that cDNA encoded human liver dehydroepiandrosterone sulfotransferase and estrogen sulfotranferase contributed to the sulfation of minoxidil.

Journal ArticleDOI
TL;DR: The bifurcation in mechanism of action of this large set of diverse phenols is novel and unusual and suggests that two distinct processes are operative and non-specific toxicity as modulated by hydrophobicity, appears to predominate.

Journal ArticleDOI
TL;DR: In this article, the gamma-glutamylcysteine synthetase inhibitor buthionine sulfoximine was used to selectively target tumors while sparing normal tissues.