Abstract：
:A series of 13 cyclopenta polycyclic aromatic hydrocarbons have been studied using quantum mechanical methods. The three-dimensional molecular structure of each carbocation that might result from the opening of a protonated epoxide ring formed between the carbon atoms completing the cyclopenta ring was computed with AM1. AM1 and ab initio calculations, using a split valence basis set, were then used to predict the direction of ring opening and obtain information about the reactivity of the carbocation. These calculations have shown that for all carbocations studied the cationic charge is well distributed throughout the molecule. The largest CH group charges are approximately 0.3 electron. If the protonated epoxide ring can open so that the nominal charge is on a CH group that is attached to the central ring of an anthracenic core, that carbocation will be greatly favored. For carbocations of this type, the unoccupied alpha' position (the CH group opposite the position of attachment to the anthracenic core) has as much or more of the cation charge as the nominally charged CH position. The group charges, and other properties related to electrostatic reactivity, clearly favor addition of nucleophiles at the unoccupied alpha' position over addition at the nominally charged position. However, when the addition of small nucleophiles at both of these positions is modeled for two such examples, the results favor addition at the nominally charged position in one case and are equivocal in the other case. The group charges and other reactivities considered characterize the electrostatic part of the interaction.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Rabinowitz JR,Little SBdoi
10.1021/tx00026a022subject
Has Abstractpub_date
1992-03-01 00:00:00pages
286-92issue
2eissn
0893-228Xissn
1520-5010journal_volume
5pub_type
杂志文章abstract：:It is vital that methylated trivalent arsenicals [MA(III) and DMA(III)] are described and characterized unequivocally due to their high toxicity. Two different ways of generating the methylated trivalent arsenicals have been practiced-reduction of the methylated pentavalent arsenical either by the sodium-metabisulfite...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx049978q
更新日期：2004-08-01 00:00:00
abstract：:PAHs (polycyclic aromatic hydrocarbons) are suspect lung cancer carcinogens that must be metabolically converted into DNA-reactive metabolites. P4501A1/P4501B1 plus epoxide hydrolase activate PAH to (+/-)- anti-benzo[ a]pyrene diol epoxide ((+/-)- anti-BPDE), which causes bulky DNA adducts. Alternatively, aldo-keto re...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx700404a
更新日期：2008-05-01 00:00:00
abstract：:Free-radical oxidation of human plasma low-density lipoprotein (LDL) produces (carboxyalkyl)pyrrole (CAP) epitopes that were detected with enzyme-linked immunosorbent assays using antibodies raised against keyhole limpet hemocyanin (KLH)-bound 2-(omega-carboxyheptyl)-pyrrole (CHP) and 2-(omega-carboxypropyl)pyrrole (C...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx970112c
更新日期：1997-12-01 00:00:00
abstract：:Experimental and epidemiological data associate the exposure of estrogens to cancer development in several tissues, particularly, the breast, endometrium, liver, and kidney. One plausible mechanism of estrogen-mediated carcinogenicity is DNA damage by redox cycling of estrogen catechols. Reports have shown that metabo...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx200356v
更新日期：2012-02-20 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：:3'-Hydroxyacetanilide (AMAP) is a nonhepatotoxic regioisomer of acetaminophen (APAP) that nonetheless does form reactive metabolites which bind to hepatic proteins. Because differences in the nature of reactive metabolites formed from AMAP and APAP may explain differences in their propensity to cause hepatotoxicity, c...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00007a007
更新日期：1989-01-01 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：:2,5-Hexanedione (2,5-HD) is the neurotoxic gamma-diketone metabolite of the industrial solvent n-hexane. Substantial evidence indicates that 2,5-HD reacts with neurofilament protein lysine epsilon-amines to yield 2,5-dimethylpyrrole adducts and that this reaction is critical to the mechanism of toxicity. Alkylpyrroles...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00040a011
更新日期：1994-07-01 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：:A well-defined silica nanoparticle model system was developed to study the effect of the size and structure of aggregates on their membranolytic activity. The aggregates were stable and characterized using transmission electron microscopy, dynamic light scattering, nitrogen adsorption, small-angle X-ray scattering, in...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx2002178
更新日期：2011-11-21 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：:The effect of trans-1,2-dichloroethylene (DCE), an inhibitor of cytochrome P450 (P450) 2E1, on the catalytic activities and total content of hepatic P450 was determined in vivo and in vitro. Hepatic microsomes were prepared from groups of rats prior to dosing and at 2, 5, 12, and 24 h postdosing, and total P450 conten...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx970227g
更新日期：1998-07-01 00:00:00
abstract：:The mechanism of the hepatotoxicity of the analgesic acetaminophen is believed to be mediated by covalent binding to protein; however, critical targets which effect the toxicity are unknown. It has been shown that mitochondrial respiration in vivo is inhibited in mice as early as 1 h following a hepatotoxic dose of ac...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx950158a
更新日期：1996-03-01 00:00:00
abstract：:The deposition and transport of toxicants on pulmonary surfactant are important processes in human health and medical care. We have introduced classical density functional theory (CDFT) to provide insight into this process. Nine typical toxicants in PM2.5 were considered, and their free energy and structural informati...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00272
更新日期：2018-12-17 00:00:00
abstract：:The reactions of calf thymus DNA with four 1,3-dialkyl-3-acyltriazenes were studied alone or in the presence of pig liver esterase in pH 7.4 phosphate buffer for varying lengths of time. The best alkylating agent in the absence of esterase was determined to be 1,3-dimethyl-3-carbethoxytriazene (DMC), followed in order...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00028a013
更新日期：1992-07-01 00:00:00
abstract：:Although many phenols and catechols found as polyphenol natural products are antioxidants and have putative disease-preventive properties, others have deleterious health effects. One possible route to toxicity is the bioactivation of the phenolic function to quinones that are electrophilic, redox-agents capable of mod...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx200140s
更新日期：2011-09-19 00:00:00
abstract：:Marine toxins such as brevetoxins and ciguatoxins are produced by dinoflagellates and can accumulate in seafood. These toxins affect humans through seafood consumption. Intoxication is mainly characterized by gastrointestinal and neurological disorders and, in most severe cases, by cardiovascular problems. To prevent ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0342262
更新日期：2004-04-01 00:00:00
abstract：:The variability of quartz hazard stands as one of the most puzzling issues in particle toxicology, notwithstanding the fact that silicosis, the most ancient occupational disease, was the very topic from which the study of the toxicity of particulates developed. Over the years, other adverse effects of silica particles...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.6b00409
更新日期：2017-01-17 00:00:00
abstract：:The activation of phospholipase A2 (PLA2) by lipid ozonation products is reported. The principal products from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) are 1-palmitoyl-2-[8-[3(5-octyl-1,2,4-trioxolan-3-yl)octanoyl]--sn-gly cero-3- phosphocholine (PC-Criegee ozonide) and 1-palmitoyl-2-(9...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00039a026
更新日期：1994-05-01 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：: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：:Nicking of the DNA strand immediately upstream of an internal abasic (AP) site produces 5'-terminal abasic (dRp) DNA. Both the intact and the nicked abasic species are reactive intermediates along the DNA base excision repair (BER) pathway and can be derailed by side reactions. Aberrant accumulation of the 5'-terminal...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.7b00057
更新日期：2017-06-19 00:00:00
abstract：:Cyadox is a novel derivative of quinoxaline-1,4-dioxides (QdNOs) with the potential to be developed as a feed additive. However, the pharmacological and toxicological bioactive molecules of cyadox and the molecular mechanism of its pharmacological and toxic actions remain unclear. In the present study, cyadox and its ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00194
更新日期：2018-11-19 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：:Hypoxia-inducible factor-1 alpha (HIF-1 alpha) and the aryl hydrocarbon receptor (AhR) work as environmental sensors in human tissues. These proteins are members of the helix-loop-helix/Per-ARNT-SIM transcription factor family and form heterodimers with the aryl hydrocarbon receptor nuclear translocator. HIF-1 alpha c...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx7001838
更新日期：2008-02-01 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：:Platinum group metals (PGMs) is a group of metals that include platinum, palladium, rhodium, ruthenium, iridium, and osmium. Occupational respiratory exposure to platinum has been reported since 1945, but studies investigating occupational exposure to palladium, rhodium, ruthenium, iridium, and osmium are scarce. This...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/acs.chemrestox.7b00184
更新日期：2017-10-16 00:00:00
abstract：:Quartz (crystalline silica) is not consistently carcinogenic across different industries where similar quartz exposure occurs. In addition, there are reports that surface modification of quartz affects its cytotoxicity, inflammogenicity, and fibrogenicity. Taken together, these data suggest that the carcinogenicity of...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx025558u
更新日期：2002-09-01 00:00:00
abstract：:Benzo[a]pyrene diol epoxides (BPDEs) are the ultimate carcinogenic species of benzo[a]pyrene, a prototype polycyclic aromatic hydrocarbon (PAH). BPDE-modified DNA duplexes can adopt multiple conformations depending on the nature of the modified bases, the stereochemistry at the location of the covalent linkage, and th...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx050308+
更新日期：2006-02-01 00:00:00
abstract：:Lesion-induced thermodynamic destabilization is believed to facilitate β-hairpin intrusion by the human XPC/hHR23B nucleotide excision repair (NER) recognition factor, accompanied by partner-base flipping, as suggested by the crystal structure of the yeast orthologue (Min, J. H., and Pavletich, N. P. (2007) Nature 449...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx1003613
更新日期：2010-12-20 00:00:00
