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 recently reported the structures of four regioisomeric guanine-adenine adducts of DEB involving the N7 position of guanine and the N1, N3, N6, and N7 positions of adenine (Park, S., et al. (2004) Chemical Research in Toxicology 17, 1638-1651). In the present work, a novel bifunctional DNA lesion of DEB was identified as 1-(hypoxanth-1-yl)-4-(guan-7-yl)-2,3-butanediol (N1HX-N7G-BD). An authentic standard of N1HX-N7G-BD was prepared and structurally characterized by proton NMR, UV, and mass spectrometry. HPLC-ESI-MS/MS analyses of acid hydrolysates of DEB-treated calf thymus DNA revealed a peak that had the same retention time, MS/MS fragmentation, and UV spectrum as the authentic standard of N1HX-N7G-BD. We propose that N1HX-N7G-BD is formed by the hydrolytic deamination of previously reported 1-(aden-1-yl)-4-(guan-7-yl)-2,3-butanediol. Although N1HX-N7G-BD adducts are less abundant in DEB-treated DNA than the corresponding guanine-guanine cross-links, they may play a role in the induction of both AT and GC base pair mutations.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Tretyakova N,Livshits A,Park S,Bisht B,Goggin Mdoi
10.1021/tx060204esubject
Has Abstractpub_date
2007-02-01 00:00:00pages
284-9issue
2eissn
0893-228Xissn
1520-5010journal_volume
20pub_type
杂志文章abstract::The urine from mice exposed to styrene vapors (600 and 1200 mg/m(3), 6 h) was analyzed for ring-oxidized metabolites of styrene. To facilitate the identification of metabolites in urine, the following potential metabolites were prepared: 2-, 3-, and 4-vinylphenol (2-, 3-, and 4-VP), 4-vinylpyrocatechol, and 2-, 3-, an...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9004192
更新日期:2010-01-01 00:00:00
abstract::2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic aromatic amine that is formed during the cooking of meats and poultry. PhIP is a carcinogen in rodents and a potential human carcinogen. Several short-term biomarkers of PhIP have been established for human biomonitoring, but validated long-term ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx2003504
更新日期:2011-11-21 00:00:00
abstract::We have previously reported that mono- and dichlorinated biphenyls (PCBs) can be metabolized to dihydroxy compounds and further oxidized to reactive metabolites which form adducts with nitrogen and sulfur nucleophiles including DNA [Amaro et al. (1966) Chem. Res. Toxicol. 9, 623-629; Oakley et al. (1996) Carcinogenesi...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960103o
更新日期:1996-12-01 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::8-Oxo-2'-deoxyguanosine (OdG) is an abundant DNA lesion produced during oxidative damage to DNA. It can form relatively stable base pairs with both dC and dA that mimic natural dG:dC and dT:dA base pairs, respectively. Thus, when in the template strand, OdG can direct the insertion of either dCTP or dATP during replic...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300365g
更新日期:2012-11-19 00:00:00
abstract::The procarcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed during the cooking of foods. Metabolism of PhIP by CYP1A2 differs substantially between humans and rodents, with more N2-hydroxylation (activation) and less 4'-hydroxylation (detoxication) in humans....
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx050136g
更新日期:2005-09-01 00:00:00
abstract::Benzo[a]pyrene, a potent human carcinogen, is metabolized in vivo to a diol epoxide that reacts with the N2-position of guanine to produce N2-BP-dG adducts. These adducts are mutagenic causing G to T transversions. These adducts block replicative polymerases but can be bypassed by the Y-family translesion synthesis po...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00466
更新日期:2017-05-15 00:00:00
abstract::S-(1,2-Dichlorovinyl)-L-cysteine (DCVC), a mutagenic and nephrotoxic metabolite of trichloroethylene, is bioactivated to S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS) and chlorothioketene and/or 2-chlorothionoacetyl chloride by cysteine conjugate S-oxidase (S-oxidase) and cysteine conjugate beta-lyase (beta-lyase...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900219x
更新日期:2009-09-01 00:00:00
abstract::A method for the analysis of N-acetylcysteine conjugates of catechol estrogens [catechol estrogen mercapturates (CE SRs)], which are likely to be urinary markers of estrogen-induced tumors, was established in this study. The characteristics of the method that was established were (1) cleanup of urine using the immunoa...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx000182a
更新日期:2000-12-01 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::Two samples of highly pure multiwalled carbon nanotubes (MWCNTs) similar in hydrophobicity and surface reactivity were prepared with similar length, <5 μm, but markedly different diameter (9.4 vs 70 nm). The samples were compared for their cytotoxic activity, uptake, and ability to induce oxidative stress (ROS product...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200255h
更新日期:2012-01-13 00:00:00
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::We have previously reported that the diuretic thiosteroid spironolactone (SPL) inactivates rat liver microsomal cytochromes P450 [P450 (P450 3A and P450 2C11)] in a in a mechanism-based fashion, and we have identified two polar SPL metabolites (SPL-sulfinic acid and -sulfonic acid), formed in a partition ratio of appr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00024a012
更新日期:1991-11-01 00:00:00
abstract::Hepatotoxicity of allyl alcohol involves its bioactivation to acrolein and subsequent protein sulfhydryl loss and lipid peroxidation. However, the links between these events and hepatocellular death are not known. The purpose of these studies was to examine whether specific signal transduction pathways are associated ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx025655n
更新日期:2003-05-01 00:00:00
abstract::Many cyanobacterial species are able to produce cyanotoxins as secondary metabolites. Among them, microcystins (MC) are a group of around 80 congeners of toxic cyclic heptapeptides. MC-LR is the most studied MC congener, in view of its high acute hepatotoxicity and tumor promoting activity. Humans may be exposed to cy...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx2000976
更新日期:2011-06-20 00:00:00
abstract::Mitomycin C (MC), a cytotoxic anticancer drug and bifunctional DNA DNA alkylating agent, induces cross-linking of the complementary strands of DNA. The DNA interstrand cross-links (ICLs) are thought to be the critical cytotoxic lesions produced by MC. Decarbamoyl mitomycin C (DMC) has been regarded as a monofunctional...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx020044g
更新日期:2002-11-01 00:00:00
abstract::Tobacco smoking is one of the leading causes for oral cancer. Dibenzo[a,l]pyrene (DB[a,l]P), an environmental pollutant and a tobacco smoke constituent, is the most carcinogenic polycyclic aromatic hydrocarbon (PAH) tested to date in several animal models (target organs: skin, lung, ovary, and mammary tissues). We hav...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200188j
更新日期:2011-08-15 00:00:00
abstract::The DNA alkylating mechanism of PNU-159682 (PNU), a highly potent metabolite of the anthracycline nemorubicin, was investigated by gel-electrophoretic, HPLC-UV, and micro-HPLC/mass spectrometry (MS) measurements. PNU quickly reacted with double-stranded oligonucleotides, but not with single-stranded sequences, to form...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00362
更新日期:2017-02-20 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::Lindane and paraquat induce biochemical changes in the liver. In order to specify their molecular impact at the cellular level, a 300 MHz 1H NMR investigation of hepatoma cell lines Hep 3B and Hep G2 responses was performed. Cells were exposed over 24 h to 50 mg/L lindane (0.178 mM) or to 100 mg/L (0.389 mM) paraquat ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9600309
更新日期:1997-01-01 00:00:00
abstract::The synthesis, toxicity, neuroprotection, and human acetylcholinesterase (hAChE)/ human butyrylcholinesterase (hBuChE) inhibition properties of β-naphthotacrines1-14 as new drugs for Alzheimer's disease (AD) potential treatment, are reported. β-Naphthotacrines1-14 showed lower toxicity than tacrine; moreover, at the h...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400138s
更新日期:2013-06-17 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::Quinones represent a class of toxicological intermediates which can create a variety of hazardous effects in vivo, including acute cytotoxicity, immunotoxicity, and carcinogenesis. The mechanisms by which quinones cause these effects can be quite complex. Quinones are Michael acceptors, and cellular damage can occur t...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx9902082
更新日期:2000-03-01 00:00:00
abstract::Thiosemicarbazones derived from acetylpyrazines were prepared by condensing an acetylpyrazine or a ring-substituted acetylpyrazine with thiosemicarbazide. Using the same procedure, N, N-dimethylthiosemicarbazones were synthesized from acetylpyrazines and N, N-dimethylthiosemicarbazide. A total of 20 compounds (16 nove...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800182k
更新日期:2008-09-01 00:00:00
abstract::Epidemiological evidence suggests a lower incidence of Parkinson's disease in smokers than in nonsmokers. This evidence, together with the lower levels of brain monoamine oxidase (MAO) activity in smokers and the potential neuroprotective properties of MAO inhibitors, prompted studies which led to the isolation and ch...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx000224v
更新日期:2001-05-01 00:00:00
abstract::Organically modified rectorite (OREC) micro/nanoparticles can be synthesized by organic modification from calcium rectorite (Ca(2+)-REC or REC), a common form of rectorite in nature. Although REC and OREC have potential applications in food packing and drug delivery, their cytotoxicity is not clear. In the present stu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500115p
更新日期:2014-08-18 00:00:00
abstract::In aqueous media at neutral pH, the binding of two cyanide molecules per cobinamide can be described by two formation constants, Kf1 = 1.1 (±0.6) × 105 M-1 and Kf2 = 8.5 (±0.1) × 104 M-1, or an overall cyanide binding constant of ∼1 × 1010 M-2. In comparison, the cyanide binding constants for cobalamin and a fully oxi...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.7b00275
更新日期:2017-12-18 00:00:00
abstract::The effect of adduct stereochemistry on the susceptibility to hydrolysis by snake venom (VPD) and bovine spleen (SPD) phosphodiesterases was investigated with short deoxyoligonucleotides containing defined adducts derived from alkylation of the exocyclic 6-amino group of dA by polycyclic aromatic hydrocarbon diol epox...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx010092l
更新日期:2001-09-01 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::Polycyclic aromatic hydrocarbons, such as benzo[a]pyrene, are widespread environmental carcinogens of human concern. Several enzymatic systems have been shown to activate benzo[a]pyrene 7, 8-dihydrodiol, the proximate carcinogenic metabolite of benzo[a]pyrene, to a reactive species which produces both a chemiluminesce...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx000159p
更新日期:2000-11-01 00:00:00