Abstract:
:The .CCl3 radical generated during the metabolism of CCl4 is readily spin trapped in vivo and in vitro by phenyl N-tert-butylnitrone (PBN) to form the stable PBN/.CCl3 radical adduct, which can then be extracted into organic solvents and detected by ESR spectroscopy. We have used this technique to examine the proposed protective roles of Zn(II), Cr(III), and metallothionein (MT) against carbon tetrachloride toxicity in vivo. Hepatic MT, which is induced by Zn(II), has been proposed to protect against CCl4-induced cellular damage by scavenging the free radical metabolites formed. CCl4-induced hepatotoxicity was significantly suppressed in male Sprague-Dawley rats pretreated with a single dose of 5 mg/kg Zn(II) or Cr(III) according to standard serum assays for liver-specific enzymes, and hepatic MT was elevated after pretreatment with either Zn(II) or Cr(III). In vitro, no difference was detected in either the amount of CCl4-derived free radical metabolites formed or the rate at which they were formed by microsomes from rats pretreated 24 h in advance with 5 mg/kg Zn(II) or Cr(III). Extraction of rat liver with 2:1 chloroform/methanol 1 h after the administration of a 0.8 mL/kg intraperitoneal or intragastric dose of CCl4 also revealed no difference in the amount of trichloromethyl radical spin trapped in vivo following pretreatment with either Zn(II) or Cr(III). These results suggest that pretreatment with either Zn(II) or Cr(III) does not affect CCl4 metabolism nor does the MT significantly scavenge the trichloromethyl free radical metabolite.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Hanna PM,Kadiiska MB,Jordan SJ,Mason RPdoi
10.1021/tx00035a017subject
Has Abstractpub_date
1993-09-01 00:00:00pages
711-7issue
5eissn
0893-228Xissn
1520-5010journal_volume
6pub_type
杂志文章abstract::A new method was developed to quantify the levels of 1,3-butadiene (BD), butadiene monoxide (BDO), and butadiene diepoxide (BDO2) in blood. The method was based on vacuum distillation of tissues followed by analysis of the distillates using multidimensional GC/MS. Metabolites isolated from blood by vacuum distillation...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00044a002
更新日期:1995-03-01 00:00:00
abstract::The gender differences in the in vitro microsomal metabolic activation of hepatotoxic clivorine, a representative naturally occurring hepatotoxic otonecine type pyrrolizidine alkaloid, in Sprague-Dawley rats and their relation to the gender differences in susceptibility to clivorine intoxication were reported in the p...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0340302
更新日期:2003-06-01 00:00:00
abstract::Capillary liquid chromatography-continuous-flow fast atom bombardment mass spectrometry is applied to the detection of deoxynucleoside adducts of N-acetoxy-N-acetyl-2-aminofluorene. In such a configuration, normal scan and tandem mass spectrometric techniques are shown to provide useful structural information for an N...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00037a013
更新日期:1994-01-01 00:00:00
abstract::Previously, we identified two distinct metabonomic phenotypes in Sprague-Dawley rats sourced from two different rooms (colonies) in the Charles River, Raleigh facility [Robosky, L. C., Wells, D. F., Egnash, L. A., Manning, M. L., Reily, M. D., and Robertson, D. G. (2005) Metabonomic identification of two distinct phen...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700184u
更新日期:2007-10-01 00:00:00
abstract::Sulfhydration by a hydrogen sulfide anion and electrophile thiolation by reactive sulfur species (RSS) such as persulfides/polysulfides (e.g., R-S-SH/R-S-Sn-H(R)) are unique reactions in electrophilic signaling. Using 1,2-dihydroxynaphthalene-4-thioacetate (1,2-NQH2-SAc) as a precursor to 1,2-dihydroxynaphthalene-4-th...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500416y
更新日期:2015-05-18 00:00:00
abstract::Acrolein is a bifunctional electrophile, present as an ubiquitous environmental pollutant and an endogenous cellular product of lipid peroxidation. Reaction of acrolein with deoxyguanosine produces two regioisomeric DNA adducts, specifically gamma-hydroxypropanodeoxyguanosine (gamma-HOPdG) and alpha-hydroxypropanodeox...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx034066u
更新日期:2003-08-01 00:00:00
abstract::At high doses, green tea extracts and green tea's major active constituent, (-)-epigallocatechin gallate (EGCG), despite their generally perceived health benefits, have been suspected to cause hepatotoxicity in certain human populations. It has been reported that o-quinone metabolites of gallic acid or EGCG are causat...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00450
更新日期:2020-11-16 00:00:00
abstract::The activation of phospholipase A2 (PLA2) by lipid ozonation products is reported. The principal products from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) are 1-palmitoyl-2-[8-[3(5-octyl-1,2,4-trioxolan-3-yl)octanoyl]--sn-gly cero-3- phosphocholine (PC-Criegee ozonide) and 1-palmitoyl-2-(9...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00039a026
更新日期:1994-05-01 00:00:00
abstract::Although selective estrogen receptor modulators (SERMs) are useful in the treatment and prevention of breast cancer, the SERM tamoxifen has been associated with an increased risk of endometrial cancer possibly due to metabolism to electrophilic quinoids. Another SERM, arzoxifene is currently in clinical trials for the...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx049776u
更新日期:2005-02-01 00:00:00
abstract::The metabolism of genistein (4',5,7-trihydroxyisoflavone), a phytoestrogen derived from soy products, was investigated using rat and human liver microsomes and recombinant human cytochrome P450 enzymes. Metabolism of genistein by microsomes obtained from rats treated with pyridine, phenobarbital, beta-naphthoflavone, ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9802320
更新日期:1999-07-01 00:00:00
abstract::The two diastereomeric forms (5'S) and (5'R) of 5',8-cyclo-2'-deoxyguanosine have been synthesized and fully characterized. They have been used as references for the investigation of gamma-irradiation of 2'-deoxyguanosine and photolysis of 8-bromo-2'-deoxyguanosine in aqueous solutions. The observed (5'R)/(5'S) ratio ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700282x
更新日期:2007-12-01 00:00:00
abstract::Contact allergy is caused by a wide range of chemicals after skin contact. Its clinical manifestation, allergic contact dermatitis (ACD), is developed upon repeated contact with the allergen. This perspective focuses on two areas that have yielded new useful information during the last 20 years: (i) structure-activity...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx7002239
更新日期:2008-01-01 00:00:00
abstract::Cytochrome P-450 enzymes have been postulated to oxidize amines through a variety of mechanisms. One of the means of distinguishing among potential pathways involves the use of kinetic hydrogen isotope effects: low isotope effects are characteristic of aminium radical mechanisms while high values are consistent with h...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00013a004
更新日期:1990-01-01 00:00:00
abstract::Furanoid 8-epidiosbulbin E acetate (EEA) is one of the most abundant diterpenoid lactones in herbal medicine Dioscorea bulbifera L. (DB). Our early work proved that EEA could be metabolized to EEA-derived cis-enedial (EDE), a reactive intermediate, which is required for the hepatotoxicity observed in experimental anim...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00016
更新日期:2020-07-20 00:00:00
abstract::The ToxCast EPA challenge was managed by TopCoder in Spring 2014. The goal of the challenge was to develop a model to predict the lowest effect level (LEL) concentration based on in vitro measurements and calculated in silico descriptors. This article summarizes the computational steps used to develop the Rank-I model...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00481
更新日期:2016-05-16 00:00:00
abstract::Diethylstilbestrol (DES) and hexestrol (HES) are carcinogenic synthetic estrogens. The major metabolites of these compounds are their catechol derivatives, 3'-OH-DES and 3'-OH-HES. Oxidation of these metabolites leads to the electrophilic quinones, which are presumably involved in the tumor-initiating process. A synth...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx970140v
更新日期:1998-05-01 00:00:00
abstract::Previous studies suggested that lamotrigene (LTG) underwent bioactivation to a reactive aryl epoxide intermediate in rats. Nevertheless, definitive structures of these thioether conjugates, which are often needed to substantiate the mechanism of bioactivation and identity of reactive intermediate(s), were not fully es...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9003243
更新日期:2010-01-01 00:00:00
abstract::Inorganic arsenic is a strong carcinogen, possibly by interaction with the telomere length. The aim of the study was to evaluate how chronic arsenic exposure from drinking water as well as the arsenic metabolism efficiency affect the individual telomere length and the expression of telomere-related genes. Two hundred ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300222t
更新日期:2012-11-19 00:00:00
abstract::The risk factors for women developing breast and endometrial cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy in particular has been correlated with a slight increased cancer risk. Previously, we showed that equilenin, a minor component of Premarin (Wyeth-Ayerst), was metab...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx980217v
更新日期:1999-02-01 00:00:00
abstract::Titanium dioxide nanoparticles (Nano-TiO2) are gradually being used extensively in clinical settings, industry, and daily life. Accumulation studies showed that Nano-TiO2 exposure is able to cause injuries in various animal organs, including the lung, liver, spleen, and kidney. However, it remains unclear whether expo...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500287f
更新日期:2015-03-16 00:00:00
abstract::4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are important human carcinogens in tobacco products. They are metabolized to produce a variety 4-(3-pyridyl)-4-oxobutyl (POB) DNA adducts including O(2)-[4-(3-pyridyl)-4-oxobut-1-yl]thymidine (O(2)-POB-dT), the most abundant POB adduc...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00468
更新日期:2016-03-21 00:00:00
abstract::Two novel pectenotoxins (PTXs) were detected by LC-MS in solid phase extracts of net hauls taken at Flødevigen, Norway, in June 2002 that were dominated by Dinophysis acuminata and Dinophysis norvegica. The new compounds were isolated as minor components from a large collection of a Dinophysis acuta-dominated bloom ob...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx049870a
更新日期:2004-11-01 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::p,p'-DDE, the main metabolite of DDT, is notorious for its persistent and bioaccumulation. It has detrimental effects on the nervous system, while the mechanism is unclear. We sought to investigate the mechanism of p,p'-DDE-induced neurocytic apoptosis in PC12 cells by cytoflow and screen the potential target gene by ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx4003963
更新日期:2014-04-21 00:00:00
abstract::Cholyl adenylate is a putative intermediate for biosynthesis of cholic acid-coenzyme A (CoA) thioester conjugates by acyl-CoA synthetase. Early studies showed the conjugated acid anhydride moiety of cholyl adenylate to be reactive, attacking proteins to form protein-cholic acid adducts. In the present study, to clarif...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx050159v
更新日期:2005-11-01 00:00:00
abstract::Strong evidence supports the idea that specific metabolites of estrogens, mainly catechol estrogen-3,4-quinones, can react with DNA to become endogenous initiators of breast, prostate, and other human cancers. Oxidation of the catechol estrogen metabolites 4-hydroxyestradiol (4-OHE2) and 2-OHE2 leads to the quinones, ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx050229y
更新日期:2006-01-01 00:00:00
abstract::A series of tether-linked bis netropsins have been synthesized in order to assess the phasing problem, which arises because of the lack of dimensional correspondence between oligopeptides and oligonucleotides in DNA binding characteristics. The consequences of incorporating variable-length flexible and rigid tethers [...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00014a013
更新日期:1990-03-01 00:00:00
abstract::The reactions of calf thymus DNA with four 1,3-dialkyl-3-acyltriazenes were studied alone or in the presence of pig liver esterase in pH 7.4 phosphate buffer for varying lengths of time. The best alkylating agent in the absence of esterase was determined to be 1,3-dimethyl-3-carbethoxytriazene (DMC), followed in order...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00028a013
更新日期:1992-07-01 00:00:00
abstract::E-cigarette flavorings have not been thoroughly evaluated for inhalational toxicity. We have shown that the flavoring chemical cinnamaldehyde impairs human neutrophils, macrophages, and natural killer cells. Here we investigated the effects of other common e-liquid flavoring chemicals on phagocytosis and oxidative bur...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00171
更新日期:2019-06-17 00:00:00
abstract::A series of alpha-(X-substituted-methyl)-gamma,gamma-dimethyl-gamma-butyrolactones (series 1), a series of alpha-(2-X-substituted-ethyl)-gamma,gamma-dimethyl-gamma-butyrolactones (series 2), where X is a leaving group, and the compound alpha-(3-bromopropyl)-gamma,gamma-butyrolactone (3) were synthesized. Their reactio...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00039a005
更新日期:1994-05-01 00:00:00