Abstract:
:Carcinogens induce complex transcriptional responses in cells that may hold key mechanistic information. Benzo(a)pyrene (BaP) modulation of transcription may occur through the activation of the aryl hydrocarbon receptor (AHR) or through responses to DNA damage. To characterize further the expression profiles induced by BaP in HepG2 and MCF-7 cells obtained in our previous study, they were compared to those induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which activates AHR but does not bind to DNA, and anti-benzo(a)pyrene- trans-7,8-dihydrodiol-9,10-epoxide (BPDE), which binds directly to DNA but does not activate AHR. A total of 22 genes had altered expression in MCF-7 cells after both BaP and TCDD exposure, and a total of 29 genes had altered expression in HepG2 cells. In both cell lines, xenobiotic metabolism was upregulated through induction of NQO1, MGST1, and CYP1B1. A total of 78 expression changes were induced by both BaP and BPDE in MCF-7 cells, and a total of 29 expression changes were induced by both BaP and BPDE in HepG2 cells. These genes were predominantly involved in cell cycle regulation, apoptosis, and DNA repair. BaP and BPDE caused the repression of histone genes in both cell lines, suggesting that regulation of these genes is an important component of the DNA damage response. Interestingly, overlap of the BPDE and TCDD gene expression profiles was also observed. Furthermore, some genes were modulated by BaP but not by TCDD or BPDE, including induction of CRY1 and MAK, which may represent novel signaling pathways that are independent of both AHR activation and DNA damage. Promoter analysis identified candidate genes for direct transcriptional regulation by either AHR or p53. These analyses have further dissected and characterized the complex cellular response to BaP.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Hockley SL,Arlt VM,Brewer D,Te Poele R,Workman P,Giddings I,Phillips DHdoi
10.1021/tx700252nsubject
Has Abstractpub_date
2007-12-01 00:00:00pages
1797-810issue
12eissn
0893-228Xissn
1520-5010journal_volume
20pub_type
杂志文章abstract::The skeleton is a target organ for most metals. This leads to their bioaccumulation, either as storage of useful oligoelements or as a protection against damage by toxic elements. The different events leading to their accumulation in this organ, under constant remodeling, are not fully understood, nor the full subsequ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx300064m
更新日期:2012-06-18 00:00:00
abstract::In this study, the HPLC, UV-vis, LC-MS, and 1H NMR characteristics of 14 different phase II mono- and mixed conjugates of quercetin were determined, providing a useful tool in the identification of quercetin phase II metabolite patterns in various biological systems. Using these data, the phase II metabolism of querce...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx049826v
更新日期:2004-11-01 00:00:00
abstract::Covalent binding of drug reactive metabolites to neutrophils or their precursors is thought to play a role in the development of drug-induced agranulocytosis. In this study, we used immunochemical techniques to compare the covalent binding of clozapine, vesnarinone, and procainamide (three drugs associated with agranu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx050095o
更新日期:2005-09-01 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::This work reveals a novel mechanism for triplet carbonyl formation (and hence chemiluminescence) during lipid peroxidation, whose chemiluminescence has been attributed to both triplet carbonyls and singlet oxygen. As a model for polyunsaturated fatty acid hydroperoxides, we have synthesized 3-hydroperoxy-2,3-dimethyl-...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx970075p
更新日期:1997-10-01 00:00:00
abstract::We have reported [Correia et al. (1987) Arch. Biochem. Biophys. 258, 436-443] that administration of 3,5-dicarbethoxy-4-ethyl-2,6-dimethyl-1,4-dihydropyridine (DDEP) to untreated, phenobarbital (PB) pretreated, or dexamethasone (DEX) pretreated rats results in relatively selective inactivation of cytochrome P-450 (P-4...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00012a008
更新日期:1989-11-01 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::Oxidative stress is associated with the pathophysiology of many degenerative human diseases, including Alzheimer's disease, atherosclerosis, Parkinson's disease, and cancers. We discovered in our previous study that thioproline (SPro), a proline analogue, is generated in oxidant-exposed cells. With the prior observati...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00055
更新日期:2020-07-20 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::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::Acetaminophen (APAP), a commonly used analgesic, is catalyzed by cytochrome P450 (P450) enzymes to a toxic intermediate which can be trapped by glutathione. Using this approach, involvement of enzymes in the activation of APAP and their kinetics were studied. With human liver microsomes, there were three apparent Km v...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00034a019
更新日期:1993-07-01 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::In recent years, there has been an increase in the production of shellfish and in global demand for seafood as nutritious and healthy food. Unfortunately, a significant number of incidences of shellfish poisoning occur worldwide, and microalgae that produce phycotoxins are responsible for most of these. Phycotoxins in...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx200182m
更新日期:2011-11-21 00:00:00
abstract::Exposure of proteins to radicals in the presence of O(2) brings about multiple changes in the target molecules. These alterations include oxidation of side chains, fragmentation, cross-linking, changes in hydrophobicity and conformation, altered susceptibility to proteolytic enzymes, and formation of new reactive grou...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0001171
更新日期:2000-11-01 00:00:00
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::2-(Glutathion-S-yl)-1,4-benzoquinone was found to be remarkably unstable in phosphate buffer (pH 7.4) even in the absence of oxygen. Intramolecular addition of the alpha-amino group of the glutamate residue to the quinone ring yielded ultimately 2,3-(glutathion-N, S-yl)-1,4-benzoquinone and 2,6-(glutathion-N,S-yl)-1,4...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9800699
更新日期:1998-10-01 00:00:00
abstract::To reveal the roles of Y family DNA polymerases in the mutagenesis induced by oxidatively damaged DNA precursors, 2-hydroxy-dATP (2-OH-dATP) and 8-hydroxy-dGTP (8-OH-dGTP) were introduced into Escherichia coli strains deficient in the Y family polymerases, DNA polymerase IV (pol IV, encoded by the dinB gene) and DNA p...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx050046b
更新日期:2005-08-01 00:00:00
abstract::The recent guidance on "Safety Testing of Drug Metabolites" issued by the U.S. Food and Drug Administration, Center for Drug Evaluation and Research (CDER) has highlighted the importance of identifying and characterizing drug metabolites as early as possible in drug discovery and development. Furthermore, upon identif...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx8003328
更新日期:2009-02-01 00:00:00
abstract::The benzophenanthridine alkaloids nitidine and fagaronine were characterized as inhibitors of topoisomerase I function. In common with the antitumor agent camptothecin, both nitidine and fagaronine stabilized the covalent binary complex formed between calf thymus topoisomerase I and DNA. The effects of these compounds...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00036a010
更新日期:1993-11-01 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::Available studies, while limited in number, suggest that e-cigarette vaping induces oxidative stress, with one potential mechanism being the direct formation of reactive oxygen species (ROS) in e-vapor. In the present studies, we measured the formation of hydroxyl radical (•OH), the most destructive ROS, in e-vapor un...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00400
更新日期:2019-06-17 00:00:00
abstract::Paraquat (PQ) is a free radical-inducing agent commonly used as an herbicide. This study assesses the acute immunotoxicity of PQ in BALB/c mice and examines its effect on cytokine gene expression profile. It was found that single subtoxic oral doses of 2, 4, and 20 mg/kg significantly inhibited the in vitro mitogen-in...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300194t
更新日期:2012-10-15 00:00:00
abstract::The syntheses of potentially important metabolites of benzo[b]naphtho[2,1-d]thiophene ([2,1]BNT)--trans-1,2-dihydroxy-1,2-dihydrobenzo[b]naphtho[2,1- d]thiophene ([2,1]BNT-1,2-diol) and trans-3,4-dihydroxy-3,4-dihydrobenzo[b]naphtho[2,1-d]thiophene ([2,1]BNT-3,4-diol)--are described. The syntheses involved preparation...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00014a002
更新日期:1990-03-01 00:00:00
abstract::This study was designed to distinguish and evaluate the contribution of reactive metabolite and reactive oxygen species as the mechanism of metabolism-dependent valproic acid-induced in vitro cytotoxicity. The involvement of reactive oxygen species in the mechanism of in vitro cytotoxicity was examined by the addition...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9801864
更新日期:1999-04-01 00:00:00
abstract::Protein glutathionylation is an important protein post-translational modification associated with oxidative stress, in which the thiol groups of cysteine residues react with glutathione and form disulfide bonds. Glutathionylation has been shown to affect protein structure and modulate protein function, and is implicat...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5000359
更新日期:2014-05-19 00:00:00
abstract::Hypoxia-inducible factor-1α (HIF-1α) is a critical regulator of cellular responses to hypoxia. Under normoxic conditions, the cellular HIF-1α level is regulated by hydroxylation by prolyl hydroxylases (PHDs), ubiquitylation, and proteasomal degradation. During hypoxia, degradation decreases, and its intracellular leve...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300274a
更新日期:2012-10-15 00:00:00
abstract::At high doses, green tea extracts and green tea's major active constituent, (-)-epigallocatechin gallate (EGCG), despite their generally perceived health benefits, have been suspected to cause hepatotoxicity in certain human populations. It has been reported that o-quinone metabolites of gallic acid or EGCG are causat...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00450
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::N'-Nitrosonornicotine (NNN) and N-nitrosopiperidine (NPIP) are potent esophageal and nasal cavity carcinogens in rats and pulmonary carcinogens in mice. N-Nitrosopyrrolidine (NPYR) induces mainly liver tumors in rats and is a weak pulmonary carcinogen in mice. These nitrosamines may be causative agents in human cancer...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0497696
更新日期:2005-01-01 00:00:00
abstract::The cytotoxic activity of N-methyl-N-nitrosourea (MNU), streptozotocin, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was determined in cell culture by using a P388 cell growth rate inhibition assay. These agents appear to have very different activities when inhibition is related to the agent concentration in the cu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00009a006
更新日期:1989-05-01 00:00:00