Abstract:
:Diastereomeric 8,5'-cyclopurine 2'-deoxynucleosides, containing a covalent bond between the deoxyribose and the purine base, are induced in DNA by ionizing radiation. They are suspected to play a role in the etiology of neurodegeneration in xeroderma pigmentosum patients. If not repaired, the S-8,5'-cyclo-2'-deoxyguanosine lesion (S-cdG) induces Pol V-dependent mutations at a frequency of 34% in Escherichia coli. Most are S-cdG → A transitions, suggesting mis-incorporation of dTTP opposite the lesion during replication bypass, although low levels of S-cdG → T transversions, arising from mis-incorporation of dATP, are also observed. We report the structures of 5'-d(GTGCXTGTTTGT)-3'·5'-d(ACAAACAYGCAC)-3', where X denotes S-cdG and Y denotes either dA or dT, corresponding to the situation following mis-insertion of either dTTP or dATP opposite the S-cdG lesion. The S-cdG·dT mismatch pair adopts a wobble base pairing. This provides a plausible rationale for the S-cdG → A transitions. The S-cdG·dA mismatch pair differs in conformation from the dG·dA mismatch pair. For the S-cdG·dA mismatch pair, both S-cdG and dA intercalate, but no hydrogen bonding is observed between S-cdG and dA. This is consistent with the lower levels of S-cdG → T transitions in E. coli.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Huang H,Das RS,Basu AK,Stone MPdoi
10.1021/tx2005053subject
Has Abstractpub_date
2012-02-20 00:00:00pages
478-90issue
2eissn
0893-228Xissn
1520-5010journal_volume
25pub_type
杂志文章abstract::Electrophilic DNA adducts produced following oxidative stress can form DNA-protein cross-links (DPCs), dramatically altering genomic maintenance pathways. Complete characterization of DPCs has been hindered, in part, because of a lack of comprehensive techniques for their analysis. We have, therefore, established a pr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400384e
更新日期:2014-01-21 00:00:00
abstract::Aminoglutethimide (AMG) is an aromatic amine aromatase inhibitor associated with a high incidence of idiosyncratic blood dyscrasias, especially agranulocytosis. Animal models of idiosyncratic drug reactions (IDRs) represent essential tools to study these reactions; however, there is currently no valid model of idiosyn...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400224j
更新日期:2013-08-19 00:00:00
abstract::The tremendous demand of the market for carbon nanotubes has led to their massive production that presents an increasing risk through occupational exposure. Lung deposition of carbon nanotubes is known to cause acute localized pulmonary adverse effects. However, systemic cardiovascular damages associated with acute pu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5004003
更新日期:2015-03-16 00:00:00
abstract::Although the causes of Parkinson's disease (PD) are not fully understood, the consensus is that a combination of genetic and environmental factors plays a major role. The discovery that the synthetic chemical, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-derived N-methyl-4-phenylpyridinium (MPP+), recapitulates...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00422
更新日期:2021-01-26 00:00:00
abstract::Overexposure to biphenyl amine compounds, which are found in smoke and azo-dyes, is linked to the occurrence of bladder cancer. However, the molecular mechanisms of biphenyl amine compound-induced bladder cancer are still unclear. Many studies have demonstrated that overexpression of cyclooxygenase-2 (COX-2) in neopla...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx2004689
更新日期:2012-03-19 00:00:00
abstract::Exposure to inorganic arsenic (iAs) induces cancer in human lungs, urinary bladder, skin, kidney, and liver, with the majority of deaths from lung and bladder cancer. To date, cancer risk assessments for iAs have not relied on mechanistic data, as we have lacked sufficient understanding of arsenic's pharmacokinetics a...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx900343d
更新日期:2010-02-15 00:00:00
abstract::The reduced transcriptomic approach allows full dose range testing of hundreds of chemicals or mixtures using human cells or zebrafish embryos. Points of departure of genes and pathways can be used for potency ranking and to classify chemicals by disrupted biological pathways. ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00104
更新日期:2018-07-16 00:00:00
abstract::Available studies, while limited in number, suggest that e-cigarette vaping induces oxidative stress, with one potential mechanism being the direct formation of reactive oxygen species (ROS) in e-vapor. In the present studies, we measured the formation of hydroxyl radical (•OH), the most destructive ROS, in e-vapor un...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00400
更新日期:2019-06-17 00:00:00
abstract::The hepatotoxicity of Troglitazone (TGZ) has been ascribed to the formation of reactive metabolites, and the primary reactive metabolite of TGZ has been confirmed to be an o-quinone methide. Oxidation of the chromane moiety is also known to produce quinone containing metabolites. Quantum chemical studies have been per...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200110h
更新日期:2011-07-18 00:00:00
abstract::Senescence, which is irreversible cell cycle arrest, is induced by various types of DNA damage, including genotoxic stress. Senescent cells show dysregulation of tumor suppressor genes and other regulators of cellular proliferation. Activating transcription factor 3 (ATF3) plays a pleiotropic role in biological proces...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500341z
更新日期:2015-01-20 00:00:00
abstract::The two major metabolites after S-oxygenation of dimethylthiourea (dimethylaminoiminomethane sulfinic acid, DMAIMSA, and dimethylaminoiminomethane sulfonic acid, DMAIMSOA) were synthesized and tested for their reactivities in the presence of mild oxidants, aqueous iodine and acidic iodate. The stoichiometry of the iod...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx050089s
更新日期:2005-07-01 00:00:00
abstract::The kinetics and mechanisms of the hydrolysis of cysteine thiosulfinate ester (CyS(O)SCy ( x- ), x = 0-2) have been investigated by stopped-flow spectrophotometry between pH 6 and pH 14. The rate-limiting reaction of hydroxide is observed for pH < 13. More complicated kinetics are observed above pH 13, where the hydro...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700168z
更新日期:2007-09-01 00:00:00
abstract::Purine deoxyribonucleoside 3'-phosphates were reacted separately with the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide. Products resulting from the cis and trans opening of the epoxide ring by the exocyclic amino groups of deoxyadenosine and deoxyguanosine 3'-phosphates were separat...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00029a015
更新日期:1992-09-01 00:00:00
abstract::Four novel cadmium-chelating agents N,N'di(D-glucosyl)alkanediamine-N,N'-bis(carbodithioates) 4a-e were prepared as disodium salts of the general formula (CH2)n[N(CS2Na)CH2(CHOH)4CH2OH]2, where n = 7, 8, 10, and 12. They were synthesized by the reductive coupling of 2 mol of alpha-D-(+)-glucose (1) with 1 mol of the c...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx950123a
更新日期:1996-01-01 00:00:00
abstract::Diclofenac sodium (DFS), a nonsteroidal anti-inflammatory drug, is frequently used in ophthalmology, but it causes negative effects on corneas. The mechanisms underlying the toxicities to corneas remains unclear. The present study was designed to assess the cytotoxicity of DFS to human corneal epithelial (HCEP) cells ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00319
更新日期:2021-01-18 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::As metals are ubiquitous in the environment, humans are continuously exposed to them. Although some metallic ions play key roles in human physiology, most metals are redundant and are actually hazardous to humans. A frequent event in the toxicological cascade triggered by nonessential metals concerns the abrogation of...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx100276f
更新日期:2010-12-20 00:00:00
abstract::The issue of the safety of drug metabolites in humans is a complex one. In this commentary, a proposal is made regarding how to deal with drug metabolites observed in humans such that the safety of these molecules can be assured. The human radiolabeled ADME study, in which metabolites are identified and quantified in ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0602012
更新日期:2006-12-01 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::Reactive oxygen species (ROS), which can be produced during normal aerobic metabolism, can induce the formation of tandem DNA lesions, including 8,5'-cyclo-2'-deoxyadenosine (cyclo-dA) and 8,5'-cyclo-2'-deoxyguanosine (cyclo-dG). Previous studies have shown that cyclo-dA and cyclo-dG accumulate in cells and can block ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx3001576
更新日期:2012-08-20 00:00:00
abstract::(-)-Epigallocatechin gallate (EGCG) is the most abundant and biologically active polyphenol in green tea, and many of the therapeutic benefits of the beverage have been attributed to this compound. High concentrations of EGCG are cytotoxic and trigger genotoxic events in mammalian cells. Although this catechin affects...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700434v
更新日期:2008-04-01 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
pub_type: 杂志文章
doi:10.1021/tx0000163
更新日期:2000-08-01 00:00:00
abstract::Arsenic is a human carcinogen, causing skin, bladder, and lung cancers. Although arsenic in drinking water affects millions of people worldwide, the mechanism(s) of action by which arsenic causes cancers is not known. Arsenic probably exerts some toxic effects by binding with proteins. However, few experimental data a...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx034053g
更新日期:2003-07-01 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
pub_type: 杂志文章
doi:10.1021/tx010063a
更新日期:2001-07-01 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::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::Toxicity data for 82 aliphatic chemicals with an alpha,beta-unsaturated substructure were compiled. Toxicity was assessed in the 2-day Tetrahymena pyriformis population growth impairment assay. Toxic potency [log(IGC50(-1))] for most of these chemicals was in excess of baseline narcosis as quantified by the 1-octanol/...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx049833j
更新日期:2005-02-01 00:00:00
abstract::Thalidomide is an infamous teratogen and it is continuously being explored for its anticancer properties. Fibroblast growth factor receptors (FGFRs) are implicated in embryo development and cancer pathophysiology. With striking similarities observed between FGFR implicated conditions and thalidomide embryopathy, we hy...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00286
更新日期:2019-04-15 00:00:00
abstract::N(6)-(2-Hydroxy-3-buten-1-yl)-2'-deoxyadenosine (N(6)-HB-dA I) and N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (N(6),N(6)-DHB-dA) are exocyclic DNA adducts formed upon alkylation of the N(6) position of adenine in DNA by epoxide metabolites of 1,3-butadiene (BD), a common industrial and environmental che...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00166
更新日期:2015-07-20 00:00:00
abstract::The cytotoxic activity of N-methyl-N-nitrosourea (MNU), streptozotocin, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was determined in cell culture by using a P388 cell growth rate inhibition assay. These agents appear to have very different activities when inhibition is related to the agent concentration in the cu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00009a006
更新日期:1989-05-01 00:00:00