Abstract:
:Green tea catechins and hydrolyzable tannins are gaining increasing attention as chemopreventive agents. However, their mechanism of action is poorly understood. We investigated the effects of four green tea catechins and two hydrolyzable tannins on microsome-induced benzo[a]pyrene (BP)-DNA adducts and the possible structure-activity relationship. BP (1 microM) was incubated with rat liver microsomes and DNA in the presence of the test compound (1-200 microM) or vehicle. The purified DNA was analyzed by (32)P-postlabeling. The inhibitory activity of the catechins was in the following descending order: epigallocatechin gallate (IC(50) = 16 microM) > epicatechin gallate (24 microM) > epigallocatechin (146 microM) > epicatechin (462 microM), suggesting a correlation between the number of adjacent aromatic hydroxyl groups in the molecular structure and their potencies. Tannic acid (IC(50) = 4 microM) and pentagalloglucose (IC(50) = 26 microM) elicited as much DNA adduct inhibitory activity as the catechins or higher presumably due to the presence of more functional hydroxyl groups. To determine if the activity of these compounds was due to direct interaction of phenolic groups with electrophilic metabolite(s) of BP, DNA was incubated with anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) (0.5 microM) in the presence of test compounds (200 microM) or vehicle. Significant inhibition of DNA adduct formation was found (tannic acid > pentagalloglucose > epigallocatechin gallate > epicatechin gallate). This notion was confirmed by analysis of the reaction products of anti-BPDE with the catechins and pentagalloglucose by electrospray ionization mass spectrometry and liquid chromatography-mass spectrometry. In conclusion, our data demonstrate that green tea catechins and the hydrolyzable tannins are highly effective in inhibiting BP-DNA adduct formation at least, in part, due to direct interaction of adjacent hydroxyl groups in their structures and that the activity is higher with an increasing number of functional hydroxyl groups.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Cao P,Cai J,Gupta RCdoi
10.1021/tx900412asubject
Has Abstractpub_date
2010-04-19 00:00:00pages
771-7issue
4eissn
0893-228Xissn
1520-5010journal_volume
23pub_type
杂志文章abstract::Previous reports indicate that 4-benzyl-1-methyl-1,2,3,6-tetrahydropyridine (BMTP), the benzyl analogue of the Parkinsonian inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is not neurotoxic in the C-57 black mouse even when administered at a dose 10 times greater than the dose of MPTP required...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00014a008
更新日期:1990-03-01 00:00:00
abstract::( E)-4-Hydroxynon-2-enal (HNE), an electrophilic bifunctional cytotoxic lipid peroxidation product, forms covalent adducts with nucleophilic side chains of amino acid residues. HNE-derived adducts have been implicated in many pathophysiological processes including atherosclerosis, diabetes, and Alzheimer's disease. Tr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx8000303
更新日期:2008-07-01 00:00:00
abstract::A series of 13 cyclopenta polycyclic aromatic hydrocarbons have been studied using quantum mechanical methods. The three-dimensional molecular structure of each carbocation that might result from the opening of a protonated epoxide ring formed between the carbon atoms completing the cyclopenta ring was computed with A...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00026a022
更新日期:1992-03-01 00:00:00
abstract::Cryogenic (4-10 K) laser-induced vibrationless ground state and vibronic excited state fluorescence emission spectra of the adducts resulting from reaction in vitro of human serum albumin and the carcinogen (+-)-r-7,t-8-dihydroxy-c-9,c-10-epoxy-7,8,9,10- tetrahydrobenzo[a]-pyrene were recorded in order to determine th...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00025a012
更新日期:1992-01-01 00:00:00
abstract::Prolonged ingestion of Yellow Starthistle (Centaurea solstitialis) and Russian Knapweed (Centaurea repens) by horses has been shown to result in a fatal neurodegenerative disorder called equine nigropallidal encephalomalacia (ENE). Bioassay-guided fractionation of extracts from Centaurea species using the PC12 cell li...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx049864e
更新日期:2004-09-01 00:00:00
abstract::Evidence from laboratory studies and clinical trials suggests that plant-derived polyphenolic compounds such as curcumin, resveratrol, or phloretin might be useful in the treatment of certain diseases (e.g., Alzheimer's disease) and acute tissue injury states (e.g., spinal cord trauma). However, despite this potential...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.6b00300
更新日期:2016-12-19 00:00:00
abstract::The polyphenolics in green tea are believed to be the bioactive components. However, poor bioavailability following ingestion limits their efficacy in vivo. In this study, polyphenon E (poly E), a standardized green tea extract, was administered by sustained-release polycaprolactone implants (two, 2-cm implants; 20% d...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx2000625
更新日期:2011-06-20 00:00:00
abstract::Idiosyncratic drug reactions (IDRs) represent a major clinical problem, and at present, the mechanisms involved are still poorly understood. One animal model that we have used for mechanistic studies of IDRs is penicillamine-induced autoimmunity in Brown Norway (BN) rats. Previous work in our lab found that macrophage...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900087z
更新日期:2009-07-01 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
pub_type: 杂志文章
doi:10.1021/tx010181y
更新日期:2002-05-01 00:00:00
abstract::Rutaevin is one of the major bioactive constituents isolated from Evodia rutaecarpa, a well-known herbal medicine that has been widely prescribed for the treatment of gastrointestinal disorders in China. However, oral administration of rutaevin has been shown to cause hepatotoxicity in mice. Bioactivation was suggeste...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00475
更新日期:2020-12-21 00:00:00
abstract::Dysregulation in the expression of microRNAs (miRNAs), single-stranded RNAs which regulate gene expression, has been associated with diseases such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), although their cellular origin has not been explored. Thus, the focus of this work was to study expressi...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.7b00330
更新日期:2018-06-18 00:00:00
abstract::The tobacco-specific nitrosamines N'-nitrosonornicotine (NNN, 1) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 2) are potent carcinogens in rodents. Bioactivation of NNN and NNK by cytochrome P450 enzymes generates a pyridyloxobutylating agent 6, which alkylates DNA to produce pyridyloxobutyl (POB)-DNA addu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx050351x
更新日期:2006-05-01 00:00:00
abstract::Formyl chloride has been indirectly implicated as an intermediate in the oxidation of CH(2)Cl(2) and proposed to be a product of the oxidation of some other compounds. Formyl chloride was synthesized and added to aqueous solutions, with CO formed as a product. The presence of glutathione (GSH) did not reduce the yield...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx060087n
更新日期:2006-08-01 00:00:00
abstract::A correct estimate of ligand binding modes and a ratio of their occupancies is crucial for calculations of binding free energies. The newly developed method BLUES combines molecular dynamics with nonequilibrium candidate Monte Carlo. Nonequilibrium candidate Monte Carlo generates a plethora of possible binding modes a...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00030
更新日期:2019-07-15 00:00:00
abstract::Reaction of lysine with estrone 3,4-o-quinone gave a complex mixture of products. Six compounds were isolated and identified using spectroscopic techniques. Among the reaction products isolated were 4-hydroxyestrone (2), 3-aminoisoestrone (3), 3-(N-pentyl-5-amino)-isoestrone (4), 1-lysylestrone 3,4-o-iminoquinone (5),...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00041a016
更新日期:1994-09-01 00:00:00
abstract::Elevated levels of the estrone metabolite, 16α-hydroxyestrone (16αOHE1), have been linked with multiple diseases. As an electrophilic reactive metabolite, covalent binding to proteins is thought to constitute one of the possible mechanisms in the onset of deleterious health outcomes associated with 16αOHE1. Whereas ma...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00171
更新日期:2020-08-17 00:00:00
abstract::Today much is known about cytochrome P450 (P450) enzymes and their catalytic specificity, but the range of reactions catalyzed by each still continues to surprise. Historically, P450s had been considered to be involved in either the metabolism of xenobiotics or endogenous chemicals, in the former case playing a genera...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00226
更新日期:2017-01-17 00:00:00
abstract::N-Methyl-N-nitrosourea (MNU) is a reactive, mutagenic methylating agent. MNU methylates DNA at various sites, including guanine N7, guanine O6, and adenine N3. Dixit and Gold [(1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8039-8043] reported that ellagic acid, a phenolic natural product, inhibited the mutagenicity of MNU i...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00015a002
更新日期:1990-05-01 00:00:00
abstract::A potentiometric and spectroscopic (UV/vis and CD) study of Cu(II) and Ni(II) binding to the N-terminal pentadecapeptide of human protamine HP2 (HP2(1-15)) was performed. The results indicate that the N-terminal tripeptide motif Arg-Thr-His is the exclusive binding site for both metal ions at a metal to HP2(1-15) mola...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx970028x
更新日期:1997-08-01 00:00:00
abstract::alpha-Sulfate trans-tamoxifen and alpha-sulfate cis-tamoxifen were synthesized as proposed active metabolites of tamoxifen that react with DNA. alpha-Acetoxytamoxifen was prepared as a model-activated form to produce a reactive carbocation. Calf thymus DNA was reacted with alpha-hydroxytamoxifen or the activated forms...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960114h
更新日期:1997-02-01 00:00:00
abstract::8-Oxo-7,8-dihydroguanine (G(O), 8-hydroxyguanine) in DNA is one of the most important oxidatively damaged bases and causes G:C → T:A substitution mutations. The Werner syndrome protein (WRN) is a cancer-related RecQ DNA helicase and plays many roles in DNA replication and repair. To examine the relationships between G...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500418m
更新日期:2015-04-20 00:00:00
abstract::DNA-DNA cross-linking by 1,2,3,4-diepoxybutane (DEB) is considered the molecular basis for its potent cytotoxic and genotoxic effects. DEB reactions with DNA initially lead to N7-(2'-hydroxy-3',4'-epoxybut-1'-yl)-guanine monoadducts, which can then alkylate neighboring DNA bases to form bifunctional lesions. We recent...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx060204e
更新日期:2007-02-01 00:00:00
abstract::The N-reduction of the centrally acting alpha 2-adrenoreceptor agonist guanoxabenz (Benzérial), an N-hydroxyamidinohydrazone, to the amidinohydrazone guanabenz (Wytensin, Hipten, Rexitene) by microsomal fractions from rabbits, pigs and humans has been detected in vitro. The conversion rates with rabbit microsomal frac...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9502047
更新日期:1996-06-01 00:00:00
abstract::The environmental contaminant benzo[c]phenanthrene (B[c]Ph) has weak carcinogenic activity in rodent bioassays; however, the fjord region diol epoxides of B[c]Ph, B[c]Ph-3,4-diol 1,2-epoxides (B[c]PhDE), are potent carcinogens. To determine the role of cytochrome P450 isozymes in the activation of B[c]Ph in MCF-7 cell...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960174n
更新日期:1997-05-01 00:00:00
abstract::The antioxidant properties of a number of water-soluble diorganyl tellurides have been investigated. These organotellurium compounds efficiently protect against peroxynitrite-mediated oxidation of dihydrorhodamine 123, hydroxylation of benzoate, and nitration of 4-hydroxyphenyl acetate. The peroxidation of the zinc st...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx990156g
更新日期:2000-01-01 00:00:00
abstract::Estrogens can have two roles in the induction of cancer: stimulating proliferation of cells by receptor-mediated processes, and generating electrophilic species that can covalently bind to DNA. The latter role is thought to proceed through catechol estrogen metabolites, which can be oxidized to o-quinones that bind to...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960002q
更新日期:1996-07-01 00:00:00
abstract::Nuclear magnetic resonance (NMR) spectroscopy has traditionally been considered as an indispensable tool in elucidating structures of metabolites. With the advent of Fourier transform (FT) spectrometers, along with improvements in software and hardware (such as high-field magnets, cryoprobes, versatile pulse sequences...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800251p
更新日期:2009-02-01 00:00:00
abstract::n-Hexane is metabolized to the gamma-diketone 2,5-hexanedione (2,5-HD), a derivative that covalently binds to lysine residues in neurofilament (NF) protein to yield 2,5-dimethylpyrrole adducts. Studies comparing the pyrrole-forming potential and neurotoxic potency of gamma-diketones have demonstrated that pyrrolylatio...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00047a017
更新日期:1995-07-01 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
pub_type: 杂志文章
doi:10.1021/tx015556u
更新日期:2001-11-01 00:00:00
abstract::The wide pH range reported for electronic cigarette (ECIG) liquids indicates that nicotine may be present in one or more chemical forms. The nicotine form affects the bioavailability and delivery of nicotine from inhaled products. Protonated nicotine is normally associated with counteranions in tobacco products. The c...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.7b00090
更新日期:2017-08-21 00:00:00