abstract：:Raloxifene is a selective estrogen receptor modulator which is effective in the treatment of osteoporosis in postmenopausal women. We report herein that cytochrome P450 (P450)3A4 is inhibited by raloxifene in human liver microsomal incubations. The nature of the inhibition was irreversible and was NADPH- and preincuba...

journal_title：Chemical research in toxicology

authors： Chen Q,Ngui JS,Doss GA,Wang RW,Cai X,DiNinno FP,Blizzard TA,Hammond ML,Stearns RA,Evans DC,Baillie TA,Tang W

更新日期：2002-07-01 00:00:00

abstract：:The diarrhetic shellfish toxin composition in the digestive glands of mussels collected in June 2001 from the Northern Adriatic sea was investigated by high-performance liquid chromatography coupled with electrospray ion trap mass spectrometry. Along with known yessotoxins (1, 3-6), identified by comparison of their r...

journal_title：Chemical research in toxicology

authors： Ciminiello P,Dell'Aversano C,Fattorusso E,Forino M,Magno S,Poletti R

更新日期：2002-07-01 00:00:00

abstract：:In this study, human glutathione transferases (GSTs) of alpha class have been assayed with the ultimate carcinogenic (-)-anti- and (+)-syn-diol epoxides (DEs) derived from the nonplanar dibenzo[a,l]pyrene (DBPDE) and the (+)-anti-diol epoxide of the planar benzo[a]pyrene [(+)-anti-BPDE] in the presence of glutathione ...

journal_title：Chemical research in toxicology

authors： Dreij K,Sundberg K,Johansson AS,Nordling E,Seidel A,Persson B,Mannervik B,Jernström B

更新日期：2002-06-01 00:00:00

abstract：:3-(2-Deoxy-beta-D-erythro-pentofuranosyl)-6-hydroxy-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one is formed in low yield by the reaction of acrolein with 2'-deoxyguanosine. The nucleoside and an oligodeoxynucleotide containing it have been synthesized. For preparation of the nucleoside 2'-deoxyguanosine was alkyla...

journal_title：Chemical research in toxicology

authors： Nechev LV,Kozekov ID,Brock AK,Rizzo CJ,Harris TM

更新日期：2002-05-01 00:00:00

abstract：:The toxicity of paraquat (PQ2+) is attributed to intracellularly formed PQ*+, O(2)*-, H(2)O(2), and secondary.OH radicals generated through Fenton-like reactions. Yet, no antidote for PQ2+ toxicity in human has been found also due to poor cell permeability of many common antioxidants that remove toxic species predomin...

journal_title：Chemical research in toxicology

authors： Goldstein S,Samuni A,Aronovitch Y,Godinger D,Russo A,Mitchell JB

更新日期：2002-05-01 00:00:00

abstract：:Nitrofluorenes are mutagenic and carcinogenic environmental pollutants arising chiefly from combustion of fossil fuels. Nitro aromatic compounds undergo nitroreduction to N-hydroxy arylamines that bind to DNA directly or after O-esterification. This study analyzes the DNA binding and adducts from the in vitro nitrored...

journal_title：Chemical research in toxicology

authors： Ritter CL,Culp SJ,Freeman JP,Marques MM,Beland FA,Malejka-Giganti D

更新日期：2002-04-01 00:00:00

abstract：:Metabolically formed dihydrodiol epoxides in the bay-region of polycyclic aromatic hydrocarbons are thought to be responsible for the genotoxic properties of these environmental pollutants. The hexacyclic aromatic hydrocarbon dibenzo[def,mno]chrysene (anthanthrene), although lacking this structural feature, was found ...

journal_title：Chemical research in toxicology

authors： Platt KL,Degenhardt C,Grupe S,Frank H,Seidel A

更新日期：2002-03-01 00:00:00

abstract：:Water samples from the Waka River, which runs through an area housing many chemical industry facilities in Wakayama, Japan, have been found to show significant mutagenicity, especially without a mammalian metabolic activation system (S9 mix) in the Salmonella typhimurium YG1024 strain. Mutagens in the river water were...

journal_title：Chemical research in toxicology

authors： Takamura-Enya T,Watanabe T,Tada A,Hirayama T,Nukaya H,Sugimura T,Wakabayashi K

更新日期：2002-03-01 00:00:00

abstract：:Organochlorine (OC) compounds are some of the main toxicants present in the food web and target several cellular systems including the nonspecific immune system. The objective of this study was to test the hypothesis that OC compounds that activate neutrophils share common structural features. Using activation of phos...

journal_title：Chemical research in toxicology

authors： Olivero J,Bezdecny SA,Ganey PE

更新日期：2002-02-01 00:00:00

abstract：:Acrolein, a known mutagen, undergoes reaction in vitro under physiological conditions with both 2'-deoxyguanosine and native DNA to give rise to exocyclic adducts of the 5,6,7,8-tetrahydropyrimido[1,2-a]purine-10(3H)-one class having a hydroxyl group at either the 6 or the 8 position (these positions are respectively ...

journal_title：Chemical research in toxicology

authors： Huang Y,Johnson F

更新日期：2002-02-01 00:00:00

abstract：:Catalase is an important antioxidant enzyme, which has been shown to provide cardiac protection from acute toxicity induced by doxorubicin, a most effective anticancer agent. Because cumulative dose-dependent chronic cardiomyopathy due to a long-term administration of doxorubicin is a significant clinical problem, the...

journal_title：Chemical research in toxicology

authors： Kang YJ,Sun X,Chen Y,Zhou Z

更新日期：2002-01-01 00:00:00

abstract：:Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is a key bactericidal agent, but can also damage host tissue. As there is a strong link between chronic inflammation and some cancers, we have investigated HOCl damage to DNA, RNA...

journal_title：Chemical research in toxicology

authors： Hawkins CL,Davies MJ

更新日期：2002-01-01 00:00:00

abstract：:Nitric oxide (NO) has been found to inhibit the copper-responsive yeast transcription factor Ace1 in an oxygen-dependent manner. However, the mechanism responsible for NO-dependent inhibition of Ace1 remains unestablished. In the present study, the chemical interaction of nitrogen oxide species with Ace1 was examined ...

journal_title：Chemical research in toxicology

authors： Shinyashiki M,Pan CJ,Switzer CH,Fukuto JM

更新日期：2001-12-01 00:00:00

abstract：:An increased risk of breast cancer has been observed in women who consume "very well-done" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary hete...

journal_title：Chemical research in toxicology

authors： DeBruin LS,Martos PA,Josephy PD

更新日期：2001-11-01 00:00:00

abstract：:The rat esophagus is strikingly sensitive to tumor induction by nitrosamines, and it has been hypothesized that this tissue contains cytochrome P450 enzymes (P450s) which catalyze the metabolic activation of these carcinogens. The metabolic capacity of the esophagus is not well characterized. In the study described he...

journal_title：Chemical research in toxicology

authors： von Weymarn LB,Murphy SE

更新日期：2001-10-01 00:00:00

abstract：:Thiol conjugates of isothiocyanates (thiol-ITCs) are metabolites of ITCs formed in the mercapturic acid pathway in mammals. They are effective chemopreventive agents in mouse lung tumor bioassays and in other models. Thiol-ITCs are inhibitors of P450s, but it has not been determined if P450 inhibition is due to conjug...

journal_title：Chemical research in toxicology

authors： Conaway CC,Krzeminski J,Amin S,Chung FL

更新日期：2001-09-01 00:00:00

abstract：:While characterizing natural antiinflammatory substances in human placental blood, we discovered a factor that affected human neutrophils and their adherence. Rigorous chemical and stereochemical analyses revealed this factor to be the well-known alkaloid, colchicine. When samples from individual patients were analyze...

journal_title：Chemical research in toxicology

authors： Petty HR,Fernando M,Kindzelskii AL,Zarewych BN,Ksebati MB,Hryhorczuk LM,Mobashery S

更新日期：2001-09-01 00:00:00

abstract：:The effect of adduct stereochemistry on the susceptibility to hydrolysis by snake venom (VPD) and bovine spleen (SPD) phosphodiesterases was investigated with short deoxyoligonucleotides containing defined adducts derived from alkylation of the exocyclic 6-amino group of dA by polycyclic aromatic hydrocarbon diol epox...

journal_title：Chemical research in toxicology

authors： Ilankumaran P,Pannell LK,Gebreselassie P,Pilcher AS,Yagi H,Sayer JM,Jerina DM

更新日期：2001-09-01 00:00:00

abstract：:Troglitazone (TGZ), a 2,4-thiazolidinedione antidiabetic, causes hepatotoxicity in 1.9% of patients. TGZ is an inducer of, and substrate for, hepatic P450 3A. Microsomal metabolism yields a benzoquinone (TGZQ) and reactive intermediates. Kassahun et al. [Kassahun et al. (2001) Chem. Res. Toxicol. 14, 62-70] have trapp...

journal_title：Chemical research in toxicology

authors： Tettey JN,Maggs JL,Rapeport WG,Pirmohamed M,Park BK

更新日期：2001-08-01 00:00:00

abstract：:The location of carcinogen-modified nucleobases (DNA adducts) within DNA sequences is a critical factor affecting their promutagenic properties and persistence in DNA. We now report the use of controlled exonuclease digestion followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MAL...

journal_title：Chemical research in toxicology

authors： Tretyakova N,Matter B,Ogdie A,Wishnok JS,Tannenbaum SR

更新日期：2001-08-01 00:00:00

abstract：:The metabolic pathways of dietary flavonoids are still largely unknown. In the present work, mass spectrometry and UV-vis spectroscopy studies were used to show that the naturally occurring flavonoid catechin underwent enzymatic oxidation by tyrosinase in the presence of glutathione (GSH) to form mono-, bi-, and tri-g...

journal_title：Chemical research in toxicology

authors： Moridani MY,Scobie H,Salehi P,O'Brien PJ

更新日期：2001-07-01 00:00:00

abstract：:A liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) method for the measurement of aflatoxin biomarkers in urine has been developed and validated. The two major aflatoxin-DNA adducts formed in rat tissues, aflatoxin N(7)-guanine and its imidazole ring opened derivative, 8,9-dihydro-8-(2,6-diami...

journal_title：Chemical research in toxicology

authors： Walton M,Egner P,Scholl PF,Walker J,Kensler TW,Groopman JD

更新日期：2001-07-01 00:00:00

abstract：:Flucloxacillin, an isoxazolyl-penicillin, causes cholestasis and biliary epithelium injury. The aim of the study was to determine whether flucloxacillin, either directly or through metabolite formation, may induce cytotoxicity in hepatic or biliary cells. Cytotoxicity was assessed by lactate dehydrogenase release in p...

journal_title：Chemical research in toxicology

authors： Lakehal F,Dansette PM,Becquemont L,Lasnier E,Delelo R,Balladur P,Poupon R,Beaune PH,Housset C

更新日期：2001-06-01 00:00:00

abstract：:Epidemiological evidence suggests a lower incidence of Parkinson's disease in smokers than in nonsmokers. This evidence, together with the lower levels of brain monoamine oxidase (MAO) activity in smokers and the potential neuroprotective properties of MAO inhibitors, prompted studies which led to the isolation and ch...

journal_title：Chemical research in toxicology

authors： Castagnoli KP,Steyn SJ,Petzer JP,Van der Schyf CJ,Castagnoli N Jr

更新日期：2001-05-01 00:00:00

abstract：:The diarrhetic shellfish toxin composition in the digestive glands of mussels from the northern Adriatic sea was investigated. Along with known yessotoxins, identified by comparison of their chromatographic and spectral properties with those reported in the literature, we isolated a new analogue of yessotoxin, 42,43,4...

journal_title：Chemical research in toxicology

authors： Ciminiello P,Fattorusso E,Forino M,Poletti R

更新日期：2001-05-01 00:00:00

abstract：:Copper is a physiologically important, redox-active metal that may be involved in endogenous DNA damage and mutagenesis. To understand the factors that affect the location and quantity of copper-induced oxidative DNA damage in cells, we used the 5S rDNA nucleosome as a model to assess the effect of chromatin structure...

journal_title：Chemical research in toxicology

authors： Liang Q,Dedon PC

更新日期：2001-04-01 00:00:00

abstract：:Thioredoxin reductase (TR), an NADPH-dependent flavoenzyme that catalyzes the reduction of many disulfide-containing substrates, plays an important role in the cellular response to oxidative stress. Trivalent arsenicals, especially methyl As that contains trivalent arsenic (MAs(III)), are potent noncompetitive inhibit...

journal_title：Chemical research in toxicology

authors： Lin S,Del Razo LM,Styblo M,Wang C,Cullen WR,Thomas DJ

更新日期：2001-03-01 00:00:00

abstract：:Metabolic pathways of the mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) remain incompletely characterized in humans. In this study, the metabolism of MeIQx was investigated in primary human hepatocytes. Six metabolites were characterized by UV and mass spectroscopy. Novel metabolites were additionally ...

journal_title：Chemical research in toxicology

authors： Langouët S,Welti DH,Kerriguy N,Fay LB,Huynh-Ba T,Markovic J,Guengerich FP,Guillouzo A,Turesky RJ

更新日期：2001-02-01 00:00:00

abstract：:The bifunctional alkylating agent, melphalan, forms adducts on DNA that are recognized by two previously described monoclonal antibodies, MP5/73 and Amp4/42. Immunoreactivity to MP5/73 was lost when alkylated DNA was exposed to alkaline pH, while Amp4/42 only recognized the structures formed after the alkali treatment...

journal_title：Chemical research in toxicology

authors： McCartney H,Martin AM,Middleton PG,Tilby MJ

更新日期：2001-01-01 00:00:00

abstract：:A method for the analysis of N-acetylcysteine conjugates of catechol estrogens [catechol estrogen mercapturates (CE SRs)], which are likely to be urinary markers of estrogen-induced tumors, was established in this study. The characteristics of the method that was established were (1) cleanup of urine using the immunoa...

journal_title：Chemical research in toxicology

authors： Nakagomi M,Suzuki E

更新日期：2000-12-01 00:00:00

abstract：:The first method for generating (*)NO and O(2)(*)(-) at any known, constant ratio has been developed. Spermine NONOate and di(4-carboxybenzyl)hyponitrite decay with first-order kinetics and exactly equal rate constants (half-lives of 80 min) at 37 degrees C and pH 7.5 to give 200 and 40 mol % (*)NO and O(2)(*)(-), res...

journal_title：Chemical research in toxicology

authors： Hodges GR,Marwaha J,Paul T,Ingold KU

更新日期：2000-12-01 00:00:00

abstract：:Exposure of proteins to radicals in the presence of O(2) brings about multiple changes in the target molecules. These alterations include oxidation of side chains, fragmentation, cross-linking, changes in hydrophobicity and conformation, altered susceptibility to proteolytic enzymes, and formation of new reactive grou...

journal_title：Chemical research in toxicology

authors： Headlam HA,Mortimer A,Easton CJ,Davies MJ

更新日期：2000-11-01 00:00:00

abstract：:Polycyclic aromatic hydrocarbons, such as benzo[a]pyrene, are widespread environmental carcinogens of human concern. Several enzymatic systems have been shown to activate benzo[a]pyrene 7, 8-dihydrodiol, the proximate carcinogenic metabolite of benzo[a]pyrene, to a reactive species which produces both a chemiluminesce...

journal_title：Chemical research in toxicology

authors： Stansbury KH,Noll DM,Groopman JD,Trush MA

更新日期：2000-11-01 00:00:00

abstract：:Epidemiologic studies have shown causal relationships between air pollution particles and adverse health effects in susceptible subpopulations. Fly ash particles (containing water-soluble and insoluble metals) are a component of ambient air particulate pollution and may contribute to particulate-induced health effects...

journal_title：Chemical research in toxicology

authors： Prahalad AK,Inmon J,Ghio AJ,Gallagher JE

更新日期：2000-10-01 00:00:00

abstract：:The effects of hepatotoxic doses of acetaminophen on tissue concentrations of CoA in the thiol form (CoASH) and as the corresponding mixed disulfide with GSH (CoASSG) were determined to test the hypotheses that early oxidant effects of acetaminophen are expressed principally in the mitochondrial compartment and that o...

journal_title：Chemical research in toxicology

authors： Rogers LK,Valentine CJ,Szczpyka M,Smith CV

更新日期：2000-09-01 00:00:00

abstract：:To obtain definitive information about the mechanisms of urinary calculus formation and the structural characteristics of the calculi induced by biphenyl administration in rats, with a focus on the sex dependency, the constituents of the urinary calculi were analyzed by HPLC, inductively coupled plasma spectroscopy (I...

journal_title：Chemical research in toxicology

authors： Ohnishi M,Yajima H,Yamamoto S,Matsushima T,Ishii T

更新日期：2000-08-01 00:00:00

abstract：:1-Hydroxypyrene (HOP), a metabolite found in the urine of humans and laboratory animals exposed to polycyclic aromatic hydrocarbons (PAHs), is known to be both acutely toxic and genotoxic. It has been widely used as a biomarker for studying PAH exposure. In this research, we have found that, upon UVA irradiation, HOP ...

journal_title：Chemical research in toxicology

authors： Dong S,Hwang HM,Shi X,Holloway L,Yu H

更新日期：2000-07-01 00:00:00

abstract：:Exposure of individual histone proteins (H1, H2A, H2B, H3, or H4) and histone octamers (consisting of two molecules each of H2A, H2B, H3, and H4) to hydroxyl radicals, generated by gamma-irradiation, in the presence of O(2) generates protein-bound hydroperoxides in a dose-dependent fashion; this is in accord with prev...

journal_title：Chemical research in toxicology

authors： Luxford C,Dean RT,Davies MJ

更新日期：2000-07-01 00:00:00

abstract：:1H NMR spectroscopic and pattern recognition (PR)-based methods were used to investigate the biochemical variability in urine obtained from control rats and from rats treated with a hydrazine (a model hepatotoxin) or HgCl(2) (a model renal cortical toxin). The 600 MHz (1)H NMR spectra of urine samples obtained from ve...

journal_title：Chemical research in toxicology

authors： Holmes E,Nicholls AW,Lindon JC,Connor SC,Connelly JC,Haselden JN,Damment SJ,Spraul M,Neidig P,Nicholson JK

更新日期：2000-06-01 00:00:00

abstract：:Estrogen replacement therapy has been correlated with an increased risk of developing breast or endometrial cancer. 4-Hydroxyequilenin (4-OHEN) is a catechol metabolite of equilenin which is a minor component of the estrogen replacement formulation marketed under the name of Premarin (Wyeth-Ayerst). Previously, we sho...

journal_title：Chemical research in toxicology

authors： Chen Y,Liu X,Pisha E,Constantinou AI,Hua Y,Shen L,van Breemen RB,Elguindi EC,Blond SY,Zhang F,Bolton JL

更新日期：2000-05-01 00:00:00