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. Some of the pathological effects after inhalation of the particles may be due to reactive oxygen species (ROS) produced by metal-catalyzed reactions. In this investigation, we analyzed emission source particulates oil fly ash (OFA) and coal fly ash (CFA) for metal content and solubility in relation to their ability to induce 2'-deoxyguanosine (dG) hydroxylation and DNA damage as measured by 8-oxo-dG formation by HPLC/UV-electrochemical detection (ECD). Water-soluble vanadium and nickel were present at the highest concentrations, and iron was present in trace amounts in OFA (5.1% V, 1.0% Ni, and 0.4% Fe by weight). In contrast, CFA comprised mostly of water-insoluble aluminosilicates and iron (9.2% Al, 12.2% Si, and 2.8% Fe by weight). As a first approach to gain insight into the mode of action of these particulates, we examined metal species-catalyzed kinetics of dG hydroxylation. Metal species at a concentration of 0.1 mM in the incubation mixture containing 0.1 mM dG under ambient air at room temperature catalyzed maximum 8-oxo-dG formation at 15 min with yields ranging from 0.05 to 0.17%, decreasing in the following order: vanadium(IV) > iron(II) > vanadium(V) > iron(III) > or = nickel(II). Insoluble Fe(III) oxide (Fe(2)O(3)) under similar conditions had no effect. Consistent with these results, OFA rich in vanadium and nickel concentrations showed a dose-dependent increase in the level of dG hydroxylation to 8-oxo-dG formation at particulate concentrations of 0.1-1 mg/mL (p < 0.05). In contrast, CFA with high concentrations of aluminosilicates and iron did not result in a significant increase in the level of 8-oxo-dG over that of the control, i.e., dG (p > 0.05). DMSO, a (*)OH scavenger, inhibited OFA-induced 8-oxo-dG formation, and metal ion chelators, deferoxamine (DFX), DTPA, and ferrozine blocked OFA-induced 8-oxo-dG formation. OFA and CFA induced 8-oxo-dG formation in a pattern similar to that observed for dG hydroxylation when calf thymus DNA was used as a substrate. Treatment of OFA particles with DFX before reacting with DNA or addition of a catalase in the incubation mixture significantly suppressed 8-oxo-dG formation (p < 0.05). These results suggest that metal availability, but not the concentration of metals present in CFA and OFA, is critical in mediating molecular oxygen-dependent dG hydroxylation and DNA base damage.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Prahalad AK,Inmon J,Ghio AJ,Gallagher JEdoi
10.1021/tx000110jsubject
Has Abstractpub_date
2000-10-01 00:00:00pages
1011-9issue
10eissn
0893-228Xissn
1520-5010pii
tx000110jjournal_volume
13pub_type
杂志文章abstract::Acetaminophen (AP) is a popularly recommended over-the-counter analgesic-antipyretic in clinical use. However, the drug is handicapped by the occurrence of hepatotoxic insult following acute ingestion. Consequently, AP-induced hepatotoxicity is often implicated in accidental or suicidal overdose. In the current study,...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00392
更新日期:2020-02-17 00:00:00
abstract::With CO2 present in excess, ONOO- reacts to form an adduct in solution and in the solid state, most likely ONOOCO2-. In solution, the adduct appears within 2 ms and absorbs at 300 with an extinction coefficient, which is either 50% or 100% (preferred) of that of ONOO-, 1.70 × 103 M-1 cm-1, and at 685 nm with an extinc...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00068
更新日期:2018-08-20 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::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::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 synthesis of the 8 possible stereoisomeric diol epoxides (DEs) at the terminal benzo ring of carcinogenic dibenz[a,h]anthracene (DBA) is reported. trans-3,4-Dihydroxy-3,4-dihydro-DBA (1) afforded the 4 bay region DEs: the enantiomeric pairs of the anti diastereomers (+)-3/(-)-3 and of the syn diastereomers (-)-4/(...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200398b
更新日期:2011-12-19 00:00:00
abstract::Topoisomerase II regulates DNA topology by generating transient double-stranded breaks. The anticancer drug etoposide targets topoisomerase II and is associated with the formation of secondary leukemias in patients. The quinone and catechol metabolites of etoposide may contribute to strand breaks that trigger leukemic...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400205n
更新日期:2013-08-19 00:00:00
abstract::The term class effect has gained in use to describe a side effect including toxicity common to a series of drugs. There is no definition of what constitutes a class effect, and it is not applied against a rigid set of criteria.Thus, the finding of toxicity in one of a series of drugs can raise the concern of a class e...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx100408v
更新日期:2011-04-18 00:00:00
abstract::The ability of the carcinogenic mycotoxin ochratoxin A (OTA) to react with reduced glutathione (GSH) has been assessed using electrospray ionization (ES)-MS techniques. On the basis of the assumption that OTA undergoes biotransformation into the reactive quinone species OTQ (6), a synthetic sample of the reduced form ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0255929
更新日期:2002-12-01 00:00:00
abstract::The guidelines embodied in this document were revised by the editors of the Publication Division of the American Chemical Society in January 1994 and endorsed by the Society Committee on Publications. ...
journal_title:Chemical research in toxicology
pub_type: 指南,杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::The group of perylene quinone-type Alternaria toxins contains several congeners with epoxide groups, for example, altertoxin II (ATX II) and stemphyltoxin III (STTX III). Recent studies in our laboratory have disclosed that the epoxide moieties of ATX II and STTX III are reduced to alcohols in human colon Caco-2 cells...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400366w
更新日期:2014-02-17 00:00:00
abstract::Many organic sulfides (mono-, di-, and polysulfides) are present in our environment. Simple derivatives are produced by some plants and animals, while complex sulfides are secondary metabolites of several genera of bacteria and fungi. Sulfides play an important role in the smell and taste of food, and many such compou...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx200373u
更新日期:2012-01-13 00:00:00
abstract::The hydroperoxide of linoleic acid (13-HPODE) degrades to 9,12-dioxo-10(E)-dodecenoic acid (DODE), which readily modifies proteins. This study identified the major proteins in MCF7 cells modified by DODE. To reduce false positives, three methods were used to identify DODE-modified proteins. First, cells were treated w...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9002808
更新日期:2010-03-15 00:00:00
abstract::The variability of quartz hazard stands as one of the most puzzling issues in particle toxicology, notwithstanding the fact that silicosis, the most ancient occupational disease, was the very topic from which the study of the toxicity of particulates developed. Over the years, other adverse effects of silica particles...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00409
更新日期:2017-01-17 00:00:00
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::The mechanism of aromatic hydroxylation of estrogens by cytochrome P450 enzymes has been examined by comparing the oxidation of estrone with that of substrates carrying additional aromaticity such as equilenin and the structural analog 2-naphthol. Hamster liver microsomes preferentially catalyzed the conversion of est...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx970021f
更新日期:1997-07-01 00:00:00
abstract::DNA nucleobases are the prime targets for chemical modifications by endogenous and exogenous electrophiles. Alkylation of the N7 position of guanine and adenine in DNA triggers base-catalyzed imidazole ring opening and the formation of N5-substituted formamidopyrimidine (N5-R-FAPy) lesions. Me-FAPy-dG adducts induced ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00392
更新日期:2017-01-17 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
pub_type: 杂志文章
doi:10.1021/tx000178z
更新日期:2001-01-01 00:00:00
abstract::Induction of Phase II enzymes of the [Ah] gene battery by L-buthionine (S,R)-sulfoximine (BSO) and other agents was examined in mouse hepatoma Hepa-1c1c7 cells. BSO, a nonelectrophilic inhibitor of gamma-glutamylcysteine synthetase (GCS), is routinely used to examine the toxicological implications of GSH depletion. Ex...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00045a015
更新日期:1995-04-01 00:00:00
abstract::Glutathione peroxidases and their mimics, e.g., ebselen or diaryl tellurides, efficiently reduce peroxynitrite/peroxynitrous acid (ONOO-/ONOOH) to nitrite and protect against oxidation and nitration reactions. Here, we report the second-order rate constant for the reaction of the reduced form of glutathione peroxidase...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx980086y
更新日期:1998-12-01 00:00:00
abstract::2,3-Epoxy-4-hydroxynonanal (EH) is a bifunctional aldehyde formed by epoxidation of trans-4-hydroxy-2-nonenal, a peroxidation product of omega-6 polyunsaturated fatty acids. EH is mutagenic and tumorigenic and capable of modifying DNA bases forming etheno adducts in vitro. Recent studies showed that etheno adducts are...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx980107o
更新日期:1998-12-01 00:00:00
abstract::A database containing maximum daily doses of 1841 marketed oral drugs was used to examine the influence of physicochemical properties on dose and hepatotoxicity (drug induced liver injury, DILI). Drugs in the highest ∼20% dose range had significantly reduced mean lipophilicity and molecular weight, increased fractiona...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00044
更新日期:2018-06-18 00:00:00
abstract::Inhalation of environmental particulate matter (PM) is correlated with adverse health effects in humans, but gene products that couple detection with cellular responses, and the specific properties of PM that target different pathways, have not been fully elucidated. TRPA1 and V1 are two cation channels expressed by s...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200123z
更新日期:2011-06-20 00:00:00
abstract::The pharmacodynamics of rat hepatic cytochrome P450 2B (P450 2B) induction by phenobarbital (PB) and two structural congeners, dl-5-ethyl-5-phenylhydantoin (EPH) and dl-5-ethyl-5-phenyloxazolidinedione (EPO), were investigated. The in vivo induction of P450 2B was probed in F344/NCr rats by measuring immunoreactive he...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00032a008
更新日期:1993-03-01 00:00:00
abstract::The toxicity of CuO nanoparticles (NPs) to human lung epithelial (A549) cells was investigated in this study. CuO NPs (10-100 mg/L) had significant toxicity to A549 cells, whereas CuO bulk particles (BPs) showed much lower toxicity (24 h IC(50), 58 and 15 mg/L for CuO BPs and NPs, respectively). Transmission electron ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx3002093
更新日期:2012-07-16 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::A predominant pathway of xenobiotic-induced toxicity is initiated by bioactivation. Characterizing reactive intermediates will provide information on the structure of reactive species, thereby defining a potential bioactivation mechanism. Because most reactive metabolites are not stable, it is difficult to detect them...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200033v
更新日期:2011-05-16 00:00:00
abstract::A newly developed recombinant yeast strain, in which the human estrogen receptor has been stably integrated into the genome of the yeast, was used to gain information on the estrogenic activity of a large series of dietary flavonoids. Among 23 flavonoids investigated, 8 were found to markedly stimulate the transcripti...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx970170y
更新日期:1998-06-01 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::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