Abstract:
:All living organisms are exposed to xenobiotics from the environment. The exposure can lead to the formation of covalent adducts of xenobiotics or their metabolites with nucleic acids (NAs).The knowledge of NA adduct structure provides valuable information n the mechanism of carcinogenesis on a molecular level. While NMR spectroscopy is extremely successful in structural analysis of many classes of molecules ranging from small inorganic and organic molecules to large biomacromolecules, the structural analysis of NA adducts by NMR spectroscopy is accompanied by some challenges. First, the structural diversity of the adducts is very large; the electrophilic species generated from the metabolism of xenobiotics can attack various atoms of the nucleobases, and new rings are frequently formed. The second challenge in the DNA adducts structure determination is the low sensitivity of NMR spectroscopy and low amount of the adducts isolated from in vivo experiments. Recent developments of NMR hardware and experimental methods have led, however, to unprecedented sensitivity. This contribution reviews NMR techniques that are commonly applied in the determination of nucleic acid adducts structure at the nucleoside/nucleotide level. These NMR techniques and the large structural heterogeneity of NA adducts are demonstrated on recent examples (mostly published after 2000) of NA adducts structure determined by NMR. Most of the examples report 2′-deoxyribonucles(t)ide derivatives, but RNA adducts are also briefly discussed. The influence of the formation of NA adducts on nucleoside conformation (particularly syn/anti orientation of the base) is also demonstrated on recent examples.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Dracínský M,Pohl Rdoi
10.1021/tx5004535subject
Has Abstractpub_date
2015-02-16 00:00:00pages
155-65issue
2eissn
0893-228Xissn
1520-5010journal_volume
28pub_type
杂志文章,评审abstract::Exposure to arsenic affects large human populations worldwide and has been associated with a long list of human diseases, including skin, bladder, lung, and liver cancers, diabetes, and cardiovascular disorders. In addition, there are large individual differences in susceptibility to arsenic-induced diseases, which ar...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx4002868
更新日期:2013-12-16 00:00:00
abstract::Genotoxic chemicals act by causing DNA damage, which, if left unrepaired, can have deleterious consequences for cell survival. DNA damage response (DDR) gets activated to repair or mitigate the effects of DNA damage. Histone H2AX and H3 phosphorylation biomarkers (γ-H2AX and p-H3) have attracted great attention as the...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00104
更新日期:2020-08-17 00:00:00
abstract::Xenobiotics may activate the estrogen receptor, resulting in alteration of normal endocrine functions in animals and humans. Consequently, this necessitates development of assay end points capable of identifying estrogenic xenobiotics. In the present study, we screened the potential estrogenicity of chemicals via thei...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5002089
更新日期:2014-08-18 00:00:00
abstract::The measurement of metabolites constitutes a useful tool for detection of exposure and in pharmacokinetic studies. Epoxidation with subsequent glutathione conjugation and mercapturic acid formation is an important deactivation pathway for naphthalene, a toxin which presumably causes lung disease. The mercapturic acid ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00033a006
更新日期:1993-05-01 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 toxic alpha,beta-unsaturated aldehyde acrolein readily attacks proteins, generating adducts at cysteine, histidine, and lysine residues. In this study, rabbit antiserum was raised against acrolein-modified keyhole limpet hemocyanin in the expectation that it would allow immunodetection of adducted proteins in biol...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0341106
更新日期:2003-10-01 00:00:00
abstract::The purpose of this study was to investigate the degree of chlorination of catechol (CAT) derivatives of pentachlorophenol (PCP) on the induction of cytotoxicity and DNA damaging effects in calf thymus DNA (ct-DNA) and in two human breast carcinoma cell lines. Results indicated that with the addition of the transition...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0498511
更新日期:2005-02-01 00:00:00
abstract::Ochratoxin A (OTA) is a mycotoxin that shows potent nephrotoxicity and renal carcinogenicity in rodents. One hypothesis for OTA-induced tumor formation is based on its genotoxic properties that are promoted by oxidative metabolism. Like other chlorinated phenols, OTA undergoes an oxidative dechlorination process to ge...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx060138g
更新日期:2006-09-01 00:00:00
abstract::Pyridoxamine (PM) is an effective inhibitor of the formation of the carcinogen acrylamide (AA) from its precursors in low-moisture model systems. Although AA is widely assumed to act by scavenging carbonyl compounds, no alternative pathways have to date been explored. In this work, we found AA to directly react with P...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx100293y
更新日期:2011-03-21 00:00:00
abstract::Diabetes mellitus is a metabolic disorder constituting a major health problem whose prevalence has gradually increased worldwide over the past few decades. Type 2 diabetes mellitus (T2DM) remains more complex and heterogeneous and arises as a combination of insulin resistance and inadequate functional β-cell mass and ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.5b00171
更新日期:2015-09-21 00:00:00
abstract::Iron (Fe) chelation therapy was initially designed to alleviate the toxic effects of excess Fe evident in Fe-overload diseases. However, the novel toxicological properties of some Fe chelator-metal complexes have shifted appreciable focus to their application in cancer chemotherapy. Redox-inactive Fe chelator complexe...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700039c
更新日期:2007-05-01 00:00:00
abstract::Exposure to both endogenous and exogenous formaldehyde has been established to be carcinogenic, likely by virtue of forming nucleic acid and proteins adducts such as N6-formyllysine. To better assess N6-formyllysine as a biomarker of formaldehyde exposure, we studied accumulation of N6-formyllysine adducts in tissues ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.7b00075
更新日期:2017-08-21 00:00:00
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::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::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::Nitric oxide can be introduced slowly and steadily into aqueous solutions, including cell culture media, over extended periods of time via semipermeable Silastic (a registered trademark of the Dow Corning Corp.) polymer membranes. The rates of introduction are predictable and reproducible and can approach rates of nit...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00036a021
更新日期:1993-11-01 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::A transient energy impairment with resultant release and subsequent reuptake of 5-hydroxytryptamine (5-HT) and NMDA receptor activation with consequent cytoplasmic superoxide (O(2)(-)(*)), nitric oxide (NO(*)), and peroxynitrite (ONOO(-)) generation have all been implicated in a neurotoxic cascade which ultimately lea...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx020029b
更新日期:2002-10-01 00:00:00
abstract::Quantitative structure-activity relationships (QSAR's) are described for the rate of conjugation of a series of fluoronitrobenzenes with cytosolic as well as with two major alpha and mu class enzymes of rat and human liver, viz., glutathione S-transferases (GST) 1-1, 3-3, A1-1, and M1a-1a. For all purified enzymes stu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9501804
更新日期:1996-04-01 00:00:00
abstract::Nevirapine (NVP) treatment is associated with a significant incidence of skin rash in humans, and it also causes a similar immune-mediated skin rash in Brown Norway (BN) rats. We have shown that the sulfate of a major oxidative metabolite, 12-OH-NVP, covalently binds in the skin. The fact that the sulfate metabolite i...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400098z
更新日期:2013-05-20 00:00:00
abstract::Deoxyribose oxidation in DNA represents a biologically important facet of oxidative DNA damage that gives rise to protein-DNA cross-links and base adducts. Toward the goal of quantifying deoxyribose oxidation chemistry in cells, we report a method for the quantification of 3'-phosphoglycolaldehyde (PGA) residues, whic...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0341198
更新日期:2003-12-01 00:00:00
abstract::The 2'-deoxyguanosine adduct of the dietary mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been synthesized and incorporated into DNA using solid state synthesis technology. The key step to obtaining the C8-dG adduct is a palladium (Xantphos-chelated)-catalyzed N-arylation (Buchwald-Hartwig reactio...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0600191
更新日期:2006-06-01 00:00:00
abstract::Methylmercury (MeHg) reacts readily with GSH, leading to the formation of a MeHg-SG adduct that is excreted into extracellular space through multidrug-resistance-associated protein (MRP), which is regulated by the transcription factor Nrf2. We previously reported that MeHg covalently modifies Keap1 and activates Nrf2 ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5002332
更新日期:2014-10-20 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::The oral dipeptidyl peptidase 1 (DPP1) inhibitor AZD5248 showed aortic binding in a rat quantitative whole-body autoradiography (QWBA) study, and its development was terminated prior to human dosing. A mechanistic hypothesis for this finding was established invoking reactivity with aldehydes involved in the cross-link...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00236
更新日期:2015-10-19 00:00:00
abstract::Bisphenol A (BPA) is used in the production of polycarbonate plastics and epoxy resins for baby bottles, liners of canned food, and many other consumer products. Previously, BPA has been shown to reduce the activity of several antioxidant enzymes, which may contribute to oxidative stress. However, the underlying mecha...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400036v
更新日期:2013-03-18 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::DNA damage and mutations are a major primary cause of cancer. Chemical bombardment of DNA is a major contributor to DNA damage. The Division of Chemical Toxicology recently hosted a panel of researchers who provided updates on the field of chemical toxicology at the nexus of DNA damage and repair. ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00438
更新日期:2021-01-28 00:00:00
abstract::The development of a unique bioassay for cytotoxicity analysis of coal fly ash (CFA) particulate matter (PM) and its potential application for air quality monitoring is described. Using human cell lines, A549 and SK-MES-1, as live probes on microelectrode-embedded 96-well sensors, impedance changes over time are measu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00004
更新日期:2016-06-20 00:00:00
abstract::For decades, many studies have linked maternal smoking to an increased risk of preterm birth. As a result, the scientific community has long hypothesized that exposure to environmental tobacco smoke (ETS), commonly referred to as second-hand smoke, is also associated with an increased risk of preterm birth. Multiple s...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.7b00054
更新日期:2017-07-17 00:00:00