Abstract:
:Oxidized nucleobases represent one of the main classes of damage induced in DNA by ionizing radiation. Emphasis was placed in this work on the measurement of four oxidized pyrimidine bases, including 5-(hydroxymethyl)uracil (5-HMUra), 5-formyluracil (5-ForUra), 5-hydroxycytosine (5-OHCyt), and 5-hydroxyuracil (5-OHUra), in isolated DNA upon exposure to gamma radiation in aerated aqueous solution. For this purpose, both high performance liquid chromatography associated with electrochemical detection (HPLC-EC) and gas chromatography coupled to mass spectrometry (GC-MS) were used. Conditions of hydrolysis of the N-glycosidic bond were carefully checked in order to achieve a quantitative release of the lesions. We showed that 60% formic acid treatment leads to the decomposition of the four lesions studied. On the other hand, hydrolysis based on the use of either 88% formic acid or 70% hydrogen fluoride in pyridine (HF/Pyr) allowed the quantitative release of the modified bases, with the exception of 5-HMUra when the latter reagent was utilized. A dose course study of the radiation-induced formation of 5-HMUra and 5-ForUra in DNA by using the GC-MS assay showed that the latter lesion was produced in a 2.1-fold higher yield than the former one. HF/Pyr and 88% formic acid hydrolysis provided similar results for 5-ForUra, indicating the reliability of both techniques for the measurement of this lesion. For 5-OHUra and 5-OHCyt, the level of modification determined by GC-MS analysis was higher after 88% formic acid treatment than upon HF/Pyr hydrolysis. When DNA was enzymatically digested and analyzed by HPLC-EC for 5-OHdCyd and 5-OHdUrd, the results were very close to those obtained by GC-MS following HF/Pyr treatment. It was concluded that additional amounts of both 5-OHUra and 5-OHCyt are produced during the 88% formic acid treatment from radiation-induced 5,6-saturated pyrimidine precursors. It is likely that cytosine and uracil diols are involved in this reaction. The radiochemical yields of formation (in mumol.J-1) for the products studied are in the following decreasing order: 5-ForUra (0.0083) > 5-OHCyt (0.0046) > 5-HMUra (0.0039) > 5-OHUra (0.0035).
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Douki T,Delatour T,Paganon F,Cadet Jdoi
10.1021/tx960095bsubject
Has Abstractpub_date
1996-10-01 00:00:00pages
1145-51issue
7eissn
0893-228Xissn
1520-5010pii
tx960095bjournal_volume
9pub_type
杂志文章abstract::The conjugation of reactive drug metabolites to GSH is considered an important detoxification mechanism that can be spontaneous and/or mediated by glutathione S-transferases (GSTs). In case GSTs play an important role in GSH conjugation, genetically determined deficiencies in GSTs may be a risk factor for adverse drug...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx100131f
更新日期:2010-09-20 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 efficacy of 3-tert-butyl-4-hydroxyanisole (BHA) as a chemopreventive agent against chemically induced cancer or toxicity may involve the direct modulation of cytochrome P-450 dependent monooxygenase function. This hypothesis was investigated by using purified rabbit cytochrome P-450IA2 and P-450IIB4 in a reconstit...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00021a004
更新日期:1991-05-01 00:00:00
abstract::Protein-xenobiotic adducts are byproducts of xenobiotic metabolism. While there is a correlation between protein adduction and target organ toxicity, a cause and effect relationship is not often clear. Naphthoquinone (NQ) and monocrotaline pyrrole (MCTP) are two pneumotoxic electrophiles that form covalent adducts wit...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx1002436
更新日期:2010-09-20 00:00:00
abstract::Solutions of synthetic fecapentaene 12 (FP-12) intended for carcinogenicity studies were found to decompose extremely rapidly during customary dosage procedures. Apparent half-lives as short as 15 min were observed. While rates and even the qualitative course of decomposition were surprisingly variable in replicate ex...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00009a007
更新日期:1989-05-01 00:00:00
abstract::Alzheimer's disease, the most common cause of dementia, is at epidemic proportions (15 to 44% depending on age, of those age 65 to 84) in the U.S. and other developed countries but remains relatively rare in undeveloped countries. Surprisingly, solid historical data reveal the epidemic is a creature of the last centur...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.6b00373
更新日期:2017-03-20 00:00:00
abstract::The preparation and DNA binding characteristics of a structural analog of Hoechst 33258 bearing two pyridinic nitrogen atoms are described. The 1H NMR signals of the complex formed between the new ligand 1 and decadeoxyribonucleotide d(CATGGCCATG)2 were assigned by employing one- and two-dimensional NMR techniques. In...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00029a003
更新日期:1992-09-01 00:00:00
abstract::MXenes have attracted extensive attention due to their unique physicochemical properties. Especially, the flexibility and good conductivity endow MXenes with a great application prospect in the neural interfaces. However, the cytotoxicity of MXenes to nervous system remains unclear. In this study, we evaluated the cyt...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00232
更新日期:2020-12-21 00:00:00
abstract::ZnO nanoparticles (NPs) are prone to dissolution, and uncertainty remains whether biological/cellular responses to ZnO NPs are solely due to the release of Zn(2+) or whether the NPs themselves have additional toxic effects. We address this by establishing ZnO NP solubility in dispersion media (Dulbecco's modified Eagl...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx4004243
更新日期:2014-04-21 00:00:00
abstract::Coumadin (R/S-warfarin) anticoagulant therapy poses a risk to over 50 million Americans, in part due to interpersonal variation in drug metabolism. Consequently, it is important to understand how metabolic capacity is influenced among patients. Cytochrome P450s (P450 or CYP for a specific isoform) catalyze the first m...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx1000283
更新日期:2010-05-17 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::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 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::There is limited and sometimes contradictory information about the genotoxicity of the polycyclic aromatic hydrocarbon benzo[ghi]perylene (B[ghi]P). Using recently developed metabolic toxicity screening arrays and a biocolloid reactor-LC-MS/MS approach, both featuring films of DNA and human metabolic enzymes, we demon...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400147c
更新日期:2013-08-19 00:00:00
abstract::The perfluorinated carboxylic acid, perfluoro-n-decanoic acid (PFDA), is a known peroxisome proliferator which displays toxicity in rodents. Using a paired-tracer first-pass extraction technique, the effect of PFDA on hepatic glucose transport was determined in the isolated perfused rat liver. In brief, livers isolate...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00043a010
更新日期:1995-01-01 00:00:00
abstract::Successful early attrition of potential problematic compounds is of great importance in the pharmaceutical industry. The lead compound in a recent project targeting neuropathic pain was susceptible to metabolic bioactivation, which produced reactive metabolites and showed covalent binding to protein. Therefore, as a p...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5000409
更新日期:2014-06-16 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::Small particles of crystalline silicon dioxide (crystallites) are exceptionally toxic. Inhalation of quartz crystallites causes silicosis, a devastating lung disease afflicting miners, particularly coal and stone workers. Poly(vinylpyridine-N-oxide)s (PVPNOs) have been applied in the prevention and treatment of silico...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx050271t
更新日期:2006-01-01 00:00:00
abstract::So far, there is limited information on biotransformation mechanisms and products of polar contaminants in freshwater crustaceans. In the present study, metabolites of biocides and pharmaceuticals formed in Gammarus pulex and Daphnia magna were identified using liquid chromatography-high resolution mass spectrometry. ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300457f
更新日期:2013-03-18 00:00:00
abstract::The mechanisms underlying aryl hydrocarbon receptor (AHR) activation by agonists and circumstances that increase the sensitivity toward agonists and AHR inhibition by antagonists are diverse and still not fully understood. AHR antagonist, 2-methyl-2 H-pyrazole-3-carboxylic acid (2-methyl-4- o-tolylazo-phenyl)-amide, C...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00371
更新日期:2019-04-15 00:00:00
abstract::The microsomal metabolism of the carcinogen N-nitrosodimethylamine (NDMA) was suggested to be initiated by hydrogen atom abstraction to form an alpha-nitrosamino radical, which either oxidizes further to an alpha-hydroxy nitrosamine as the initial product of the activating dealkylation pathway or fragments to the nitr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00010a006
更新日期:1989-07-01 00:00:00
abstract::Chemical and structural alterations to lysozyme (LYSO), glucose 6-phosphate dehydrogenase (G6PD), and bovine eye lens proteins (BLP) promoted by peroxyl radicals generated by the thermal decomposition of 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) under aerobic conditions were investigated. SDS-PAGE analysis of...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300372t
更新日期:2013-01-18 00:00:00
abstract::Enzyme-linked immunosorbent assays (ELISAs) are reported for the detection of atrazine and its principle metabolite in human urine. The ELISAs can be used with crude urine or following extraction and partial purification by methods described in this report. GC, MS, and HPLC techniques were used to confirm and compleme...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00031a017
更新日期:1993-01-01 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::Alcohol consumption is associated with an increased risk of several types of malignancy by mechanisms that remain to be elucidated. Most of the ingested ethanol is converted to acetaldehyde but the formation of free radical metabolites such as the 1-hydroxyethyl radical has been also demonstrated to occur in vitro and...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9800351
更新日期:1998-08-01 00:00:00
abstract::The PI3K/Akt/mTOR pathway is considered to be an attractive target for the development of novel anticancer molecules. This paper reports for the first time that a small molecule, antrocin (MW = 234), from Antrodia camphorata was a potent antagonist in various cancer types, being highest in metastatic breast cancer MDA...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx100318m
更新日期:2011-02-18 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::Naphtho[8,1,2- ghi]chrysene, commonly known as naphtho[1,2- e]pyrene (N[1,2- e]P) is a widespread environmental pollutant, identified in coal tar extract, air borne particulate matter, marine sediment, cigarette smoke condensate, and vehicle exhaust. Herein, we determined the ability of rat liver microsomes to metabol...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx8000384
更新日期:2008-05-01 00:00:00
abstract::The chemical reactivity of styrene-7,8-oxide (SO), an alkylating agent with high affinity for the guanine–N7 position and a probable carcinogen for humans, with 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases, was investigated kinetically in...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5002892
更新日期:2014-10-20 00:00:00
abstract::Radionuclides represent a serious health risk to humans in the case of incorporation. To elucidate the potential of time-resolved laser-induced fluorescence spectroscopy (TRLFS) to determine the dominant radionuclide species in natural biofluids, we investigated the in vitro speciation of curium(III) in human urine sa...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx100273g
更新日期:2011-02-18 00:00:00