Abstract:
:The chemical reactivities of the optically-pure fjord-region syn- and anti-benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxides (B[g]CDEs) toward DNA in vitro have been compared with those of the optically-pure fjord-region syn- and anti-benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxides (B[c]PhDEs), using the standard 32P-postlabeling assay. The (+)-anti-, (+)-syn-, and (-)-syn-isomers of the two sets of diol epoxides showed similar extents of reaction with DNA, but the (-)-anti-B[c]PhDE was 2.5 times more reactive toward DNA than the corresponding B[g]CDE isomer and was the most reactive of the eight diol epoxides studied. When the reactions of the B[g]CDEs with DNA were analyzed by the nuclease P1-enhanced method of 32P-postlabeling, the observed adduct levels were between 3 and 10 times lower than were obtained using the standard method of 32P-postlabeling. By analyzing by TLC and HPLC the 32P-postlabeled products of the reactions of the diol epoxides with synthetic polynucleotides, the relative reactions of the B[g]CDEs and B[c]PhDEs with guanine and adenine bases in DNA were determined. All four B[g]CDE isomers reacted with adenine residues in similar proportions to those seen for the B[c]PhDE isomers. Thus, the presence of an additional benzene ring on the benzo[c]phenanthrene structure, distant from the fjord region, does not radically alter the reactivity or base selectivity of the fjord-region diol epoxides, except in the case of the (-)-anti-isomer of benzo[g]chrysene. The reasons for the lower reactivity of this isomer compared with that of the corresponding isomer of benzo[c]phenanthrene are unclear.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Giles AS,Seidel A,Phillips DHdoi
10.1021/tx00046a014subject
Has Abstractpub_date
1995-06-01 00:00:00pages
591-9issue
4eissn
0893-228Xissn
1520-5010journal_volume
8pub_type
杂志文章abstract::The dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is detoxified mainly by aldehyde dehydrogenase (ALDH). We find that the fungicide benomyl potently and rapidly inhibits ALDH and builds up DOPAL in vivo in mouse striatum and in vitro in PC12 cells and human cultured fibroblasts and glial cells. The in vi...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5002223
更新日期:2014-08-18 00:00:00
abstract::Quantum dots (QDs) are a novel class of inorganic fluorophores which are gaining widespread recognition as a result of their exceptional photophysical properties and their applications as a biomarker and in molecular biomedical imaging. The aim of this study was to evaluate the in vivo genotoxicity in mice exposed to ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx2000015
更新日期:2011-05-16 00:00:00
abstract::Peroxynitrite (PN), a very reactive oxidant formed by the combination of superoxide and nitric oxide, appears to play a role in producing tissue damage in a number of inflammatory conditions. Pharmacological scavenging and decomposition of PN within these areas has therapeutic value in several tissue injury models. Re...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx990159t
更新日期:2000-04-01 00:00:00
abstract::( E)-4-Hydroxynon-2-enal (HNE), an electrophilic bifunctional cytotoxic lipid peroxidation product, forms covalent adducts with nucleophilic side chains of amino acid residues. HNE-derived adducts have been implicated in many pathophysiological processes including atherosclerosis, diabetes, and Alzheimer's disease. Tr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx8000303
更新日期:2008-07-01 00:00:00
abstract::The process of disinfecting drinking water inadvertently leads to the formation of numerous disinfection byproducts (DBPs). Some of these are mutagenic, genotoxic, teratogenic, and cytotoxic, as well as potentially carcinogenic both in vivo and in vitro. We investigated the in vitro biological activity of five DBPs: t...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00283
更新日期:2015-10-19 00:00:00
abstract::Retinyl palmitate (RP) is frequently used as an ingredient in cosmetics and other retail products. We previously reported that, under UVA light irradiation, RP is facilely decomposed into multiple products, including anhydroretinol (AR) and 5,6-epoxyretinyl palmitate (5,6-epoxy-RP). We also determined that combined tr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0600907
更新日期:2006-11-01 00:00:00
abstract::Enzymatic methylation of cytosine residues in DNA, in conjunction with covalent histone modifications, establishes an epigenetic code essential for the proper control of gene expression in higher organisms. Once established during cellular differentiation, the epigenetic code must be faithfully transmitted to progeny ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900027w
更新日期:2009-06-01 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 effects of hepatotoxic doses of acetaminophen on tissue concentrations of CoA in the thiol form (CoASH) and as the corresponding mixed disulfide with GSH (CoASSG) were determined to test the hypotheses that early oxidant effects of acetaminophen are expressed principally in the mitochondrial compartment and that o...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0000926
更新日期:2000-09-01 00:00:00
abstract::Hemoglobin adducts have been used to assess exposure to carcinogenic compounds in tobacco smoke. However, because of background levels in nonsmokers, most adducts that have been studied are not useful for monitoring low-level exposure. Bergmark [(1997) Chem. Res. Toxicol. 10, 78-84] showed that the level of adducts of...
journal_title:Chemical research in toxicology
pub_type: 临床试验,杂志文章
doi:10.1021/tx9900728
更新日期:1999-10-01 00:00:00
abstract::The carcinogen 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) alkylates DNA at dGuo, dAdo, and dCyd. dCyd adducts, formed in small amounts, elute near the more abundant dGuo adducts. We isolated the dCyd adducts formed with dCMP. Each BPDE enantiomer forms three major adducts with dCMP, two...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0340201
更新日期:2004-04-01 00:00:00
abstract::Furan has been found in a number of heated food items and is carcinogenic in the liver of rats and mice. Estimates of human exposure on the basis of concentrations measured in food are not reliable because of the volatility of furan. A biomarker approach is therefore indicated. We searched for metabolites excreted in ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx7004212
更新日期:2008-03-01 00:00:00
abstract::Unpredicted human safety events in clinical trials for new drugs are costly in terms of human health and money. The drug discovery industry attempts to minimize those events with diligent preclinical safety testing. Current standard practices are good at preventing toxic compounds from being tested in the clinic; howe...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.9b00335
更新日期:2020-01-21 00:00:00
abstract::The reaction of the alpha, beta-unsaturated ketones methyl vinyl ketone (MVK) and ethyl vinyl ketone (EVK) with nucleosides and 5'-mononucleotides was studied. The genotoxic activity of MVK and EVK in the SOS Chromotest was investigated. Three different types of adducts with deoxyguanosine were found and their structu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00019a007
更新日期:1991-01-01 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::Tetrabromobisphenol A, a brominated flame retardant, is increasingly prevalent worldwide and presents a potential health risk. Adjusted animal biomonitoring equivalents of tetrabromobisphenol A after orally administered doses in humanized-liver mice were scaled up to humans using known species allometric scaling facto...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00358
更新日期:2020-11-16 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::Understanding the molecular basis of inorganic chemical toxicity has lagged behind the proliferation of detailed mechanisms that explain the biochemical toxicology of many organic xenobiotics. In this perspective, general barriers to explicating the bioinorganic chemistry of toxic metals are considered, followed by a ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00328
更新日期:2017-01-17 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 mechanism of formation of etheno (epsilon) adducts of nucleic acid bases from 2-haloacetaldehydes is generally assumed to occur via initial Schiff base formation resulting from reaction of the aldehyde with an exocyclic amine. We recently revised the 1H NMR assignments of the epsilon protons of 1,N2-epsilon-Guo (G...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00038a014
更新日期:1994-03-01 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::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
abstract::Adverse effects of drugs (AEDs) continue to be a major cause of drug withdrawals in both development and postmarketing. While liver-related AEDs are a major concern for drug safety, there are few in silico models for predicting human liver toxicity for drug candidates. We have applied the quantitative structure-activi...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900451r
更新日期:2010-04-19 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::Monosubstituted isopropylated triaryl phosphate (mITP) is a major component of Firemaster 550, an additive flame retardant mixture commonly used in polyurethane foams. Developmental toxicity studies in zebrafish established mITP as the most toxic component of FM 550, which causes pericardial edema and heart looping fa...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00423
更新日期:2017-02-20 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 environmental contaminant benzo[c]phenanthrene (B[c]Ph) has weak carcinogenic activity in rodent bioassays; however, the fjord region diol epoxides of B[c]Ph, B[c]Ph-3,4-diol 1,2-epoxides (B[c]PhDE), are potent carcinogens. To determine the role of cytochrome P450 isozymes in the activation of B[c]Ph in MCF-7 cell...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960174n
更新日期:1997-05-01 00:00:00
abstract::Kinetic simulation can help obtain deeper insight into the molecular mechanisms of complex processes, such as lipid peroxidation (LPO) in low-density lipoprotein (LDL). We have previously set up a single-compartment model of this process, initiating with radicals generated externally at a constant rate to show the int...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9700073
更新日期:1997-06-01 00:00:00
abstract::The current study examined the bioactivation potential of a nonpeptidyl thrombopoietin receptor agonist, 1-(3-chloro-5-((4-(4-fluoro-3-(trifluoromethyl)phenyl)thiazol-2-yl)carbamoyl)pyridine-2-yl)piperidine-4-carboxylic acid (1), containing a 2-carboxamido-4-arylthiazole moiety in the core structure. Toxicological ris...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700270r
更新日期:2007-12-01 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