p,p'-DDE induces apoptosis through the modulation of tumor necrosis factor α in PC12 cells.


:p,p'-DDE, the main metabolite of DDT, is notorious for its persistent and bioaccumulation. It has detrimental effects on the nervous system, while the mechanism is unclear. We sought to investigate the mechanism of p,p'-DDE-induced neurocytic apoptosis in PC12 cells by cytoflow and screen the potential target gene by microarray and ELISA. Co-incubation with antagonist and SiRNA were applied to confirm the effect of the selected molecular. Results were also confirmed in zebrafish embryo. Results showed that p,p'-DDE induced apoptosis in PC12 cells at a concentration of ≥2 × 10(-5) mol/L. Microarray results indicate that the TNF family plays a key role in p,p'-DDE-induced apoptosis among 84-apoptotic genes. In particular, the protein level of TNFα increased 4-fold. When incubated with TNFα antibody (infliximab), the number of apoptotic cells attenuated by 50%, and both activities of caspases 8 and 9 decreased. SiRNA silencing of TNFα showed similar trends. Furthermore, p,p'-DDE induced neuronal apoptosis in zebrafish embryos in a dose-dependent manner.This effect was partially reversed by infliximab, too. Overall, the present study herein indicated that the TNFα signaling pathway is involved in p,p'-DDE-induced neurocyte apoptosis. These data could be expanded to other cases of OCP-induced apoptosis and would support the need for scientific intervention to address the neurotoxicity of these chemicals.


Chem Res Toxicol


Wang C,Zhang Q,Qian Y,Zhao M




Has Abstract


2014-04-21 00:00:00












  • Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics.

    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


    authors: Patten CJ,Thomas PE,Guy RL,Lee M,Gonzalez FJ,Guengerich FP,Yang CS

    更新日期:1993-07-01 00:00:00

  • Interaction of trivalent arsenicals with metallothionein.

    abstract::Arsenic is a human carcinogen, causing skin, bladder, and lung cancers. Although arsenic in drinking water affects millions of people worldwide, the mechanism(s) of action by which arsenic causes cancers is not known. Arsenic probably exerts some toxic effects by binding with proteins. However, few experimental data a...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Jiang G,Gong Z,Li XF,Cullen WR,Le XC

    更新日期:2003-07-01 00:00:00

  • Dihydroxy-, hydroxyspirolactone-, and dihydroxyspirolactone-urochlorins induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the liver of mice.

    abstract::Previous work has shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes porphyria, enhanced by iron, in C57BL/6J mice with marked accumulation in the liver of uroporphyrin I and III isomers and heptacarboxylic acid III and is one model of human porphyria cutanea tarda. Preliminary examination by HPLC also indic...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Lim CK,Danton M,Clothier B,Smith AG

    更新日期:2006-12-01 00:00:00

  • Cu(II)/H2O2-induced DNA damage is enhanced by packaging of DNA as a nucleosome.

    abstract::Copper is a physiologically important, redox-active metal that may be involved in endogenous DNA damage and mutagenesis. To understand the factors that affect the location and quantity of copper-induced oxidative DNA damage in cells, we used the 5S rDNA nucleosome as a model to assess the effect of chromatin structure...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Liang Q,Dedon PC

    更新日期:2001-04-01 00:00:00

  • Mechanisms of chlorophyllin anticarcinogenesis against aflatoxin B1: complex formation with the carcinogen.

    abstract::Chlorophyllin (CHL), a food-grade derivative of the green plant pigment chlorophyll, has recently been shown in this laboratory to be a potent inhibitor in vivo of hepatic aflatoxin B1 (AFB1)-DNA adduction and hepatocarcinogenesis (Breinholt et al. (1995) Cancer Res. 55, 57-62). We report here that CHL forms a strong ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Breinholt V,Schimerlik M,Dashwood R,Bailey G

    更新日期:1995-06-01 00:00:00

  • Urine metabolites reflect time-dependent effects of cyclosporine and sirolimus on rat kidney function.

    abstract::The clinical use of the immunosuppressant calcineurin inhibitor cyclosporine is limited by its nephrotoxicity. This is enhanced when combined with the immunosuppressive mTOR inhibitor sirolimus. Nephrotoxicity of both drugs is not yet fully understood. The goal was to gain more detailed mechanistic insights into the t...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Klawitter J,Bendrick-Peart J,Rudolph B,Beckey V,Klawitter J,Haschke M,Rivard C,Chan L,Leibfritz D,Christians U,Schmitz V

    更新日期:2009-01-01 00:00:00

  • Quantitation of pyridyloxobutyl DNA adducts of tobacco-specific nitrosamines in rat tissue DNA by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

    abstract::The tobacco-specific nitrosamines N'-nitrosonornicotine (NNN, 1) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 2) are potent carcinogens in rodents. Bioactivation of NNN and NNK by cytochrome P450 enzymes generates a pyridyloxobutylating agent 6, which alkylates DNA to produce pyridyloxobutyl (POB)-DNA addu...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Lao Y,Villalta PW,Sturla SJ,Wang M,Hecht SS

    更新日期:2006-05-01 00:00:00

  • Mass spectrometry-based metabolic profiling of rat urine associated with general toxicity induced by the multiglycoside of Tripterygium wilfordii Hook. f.

    abstract::We propose here a combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) metabolic profiling strategy to elucidate the toxicity in rats induced by orally administered multiglycosides of Tripterygium wilfordii Hook. f. (GTW) in multiple organs including the kidney, liv...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Chen M,Ni Y,Duan H,Qiu Y,Guo C,Jiao Y,Shi H,Su M,Jia W

    更新日期:2008-02-01 00:00:00

  • Improved efficacy of acylfulvene in colon cancer cells when combined with a nuclear excision repair inhibitor.

    abstract::The efficacy of DNA-damaging anticancer drugs is highly influenced by cellular DNA repair capacity, and by inhibiting the relevant DNA repair pathway, efficacy of alkylating agents may be increased. Therefore, combining DNA repair inhibitors with anticancer agents that selectively target tumor tissue should improve ca...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: van Midwoud PM,Sturla SJ

    更新日期:2013-11-18 00:00:00

  • Identification of 4-S-Cysteinyltetrodotoxin from the liver of the puffer fish, Fugu pardalis, and formation of thiol adducts of tetrodotoxin from 4,9-anhydrotetrodotoxin.

    abstract::The metabolic pathway of tetrodotoxin (TTX), a powerful and specific voltage-gated sodium channel blocker, has not been well-clarified either in TTX-poisoned patients or in puffer fish. 4-S-CysteinylTTX (4-CysTTX) was isolated from the liver of the puffer fish, Fugu pardalis, as the first adduct of TTX with thiol. The...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Yotsu-Yamashita M,Goto A,Nakagawa T

    更新日期:2005-05-01 00:00:00

  • The stepwise process of chromium-induced DNA breakage: characterization by electrochemistry, atomic force microscopy, and DNA electrophoresis.

    abstract::DNA conformational change and breakage induced by Cr(VI)-GSH interaction were characterized by the integrated tools of electrochemistry, atomic force microscopy (AFM), and DNA electrophoresis. While electrochemistry confirmed the formation of the active species generated from Cr(VI)-GSH reduction, which causes the DNA...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Yang PH,Gao HY,Cai J,Chiu JF,Sun H,He QY

    更新日期:2005-10-01 00:00:00

  • Comparative evaluation of the bioreactivity and mutagenic spectra of acrolein-derived alpha-HOPdG and gamma-HOPdG regioisomeric deoxyguanosine adducts.

    abstract::Acrolein is a bifunctional electrophile, present as an ubiquitous environmental pollutant and an endogenous cellular product of lipid peroxidation. Reaction of acrolein with deoxyguanosine produces two regioisomeric DNA adducts, specifically gamma-hydroxypropanodeoxyguanosine (gamma-HOPdG) and alpha-hydroxypropanodeox...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Sanchez AM,Minko IG,Kurtz AJ,Kanuri M,Moriya M,Lloyd RS

    更新日期:2003-08-01 00:00:00

  • Impact of Physicochemical Properties on Dose and Hepatotoxicity of Oral Drugs.

    abstract::A database containing maximum daily doses of 1841 marketed oral drugs was used to examine the influence of physicochemical properties on dose and hepatotoxicity (drug induced liver injury, DILI). Drugs in the highest ∼20% dose range had significantly reduced mean lipophilicity and molecular weight, increased fractiona...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Leeson PD

    更新日期:2018-06-18 00:00:00

  • Studies on the chemical reactivity of 2-phenylpropionic acid 1-O-acyl glucuronide and S-acyl-CoA thioester metabolites.

    abstract::Chemically reactive species formed from the metabolism of carboxylic acid-containing compounds have been proposed as mediators of their toxic side-effects. Two alternative metabolic pathways known to be involved in the generation of reactive acylating metabolites of carboxylic acids are acyl glucuronidation and acyl-C...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Li C,Benet LZ,Grillo MP

    更新日期:2002-10-01 00:00:00

  • Mechanism-based inactivation of human cytochromes p450s: experimental characterization, reactive intermediates, and clinical implications.

    abstract::The P450 type cytochromes are responsible for the metabolism of a wide variety of xenobiotics and endogenous compounds. Although P450-catalyzed reactions are generally thought to lead to detoxication of xenobiotics, the reactions can also produce reactive intermediates that can react with cellular macromolecules leadi...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章,评审


    authors: Hollenberg PF,Kent UM,Bumpus NN

    更新日期:2008-01-01 00:00:00

  • Oxidative conversion by rat liver microsomes of 2-naphthyl isothiocyanate to 2-naphthyl isocyanate, a genotoxicant.

    abstract::The present study investigated the oxidative metabolism of 2-naphthyl isothiocyanate catalyzed by rat liver microsomes. Incubation of 2-naphthyl isothiocyanate, microsomes, and NADPH yielded either N,N'-di-2-naphthylurea or, on inclusion of 2-aminofluorene in the incubations, N-2-naphthyl-N'-2-fluorenylurea. These ure...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Lee MS

    更新日期:1992-11-01 00:00:00

  • Organophosphorus pesticide chlorpyrifos and its metabolites alter the expression of biomarker genes of differentiation in D3 mouse embryonic stem cells in a comparable way to other model neurodevelopmental toxicants.

    abstract::There are discrepancies about whether chlorpyrifos is able to induce neurodevelopmental toxicity or not. We previously reported alterations in the pattern of expression of biomarker genes of differentiation in D3 mouse embryonic stem cells caused by chlorpyrifos and its metabolites chlorpyrifos-oxon and 3,5,6-trichlor...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Estevan C,Fuster E,Del Río E,Pamies D,Vilanova E,Sogorb MA

    更新日期:2014-09-15 00:00:00

  • Acrylamide Induces Senescence in Macrophages through a Process Involving ATF3, ROS, p38/JNK, and a Telomerase-Independent Pathway.

    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


    authors: Kim KH,Park B,Rhee DK,Pyo S

    更新日期:2015-01-20 00:00:00

  • Slow-binding inhibition of carboxylesterase and other serine hydrolases by chlorodifluoroacetaldehyde.

    abstract::The chlorofluorocarbon substitute 1,2-dichloro-1,1-difluoroethane (HCFC-132b) undergoes oxidative metabolism in rats to give a range of metabolites, including chlorodifluoroacetaldehyde [Harris and Anders (1991) Chem. Res. Toxicol. 4, 180]. The present experiments were undertaken after studies to characterize an unide...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Yin H,Jones JP,Anders MW

    更新日期:1993-09-01 00:00:00

  • Coumarin metabolism by rat esophageal microsomes and cytochrome P450 2A3.

    abstract::The rat esophagus is strikingly sensitive to tumor induction by nitrosamines, and it has been hypothesized that this tissue contains cytochrome P450 enzymes (P450s) which catalyze the metabolic activation of these carcinogens. The metabolic capacity of the esophagus is not well characterized. In the study described he...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: von Weymarn LB,Murphy SE

    更新日期:2001-10-01 00:00:00

  • New urinary metabolites formed from ring-oxidized metabolic intermediates of styrene.

    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


    authors: Linhart I,Mráz J,Scharff J,Krouzelka J,Dusková S,Nohová H,Vodicková L

    更新日期:2010-01-01 00:00:00

  • Inhibition of the alpha-ketoglutarate dehydrogenase and pyruvate dehydrogenase complexes by a putative aberrant metabolite of serotonin, tryptamine-4,5-dione.

    abstract::A transient energy impairment with resultant release and subsequent reuptake of 5-hydroxytryptamine (5-HT) and NMDA receptor activation with consequent cytoplasmic superoxide (O(2)(-)(*)), nitric oxide (NO(*)), and peroxynitrite (ONOO(-)) generation have all been implicated in a neurotoxic cascade which ultimately lea...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Jiang XR,Dryhurst G

    更新日期:2002-10-01 00:00:00

  • Chalcone inhibition of anthracycline secondary alcohol metabolite formation in rabbit and human heart cytosol.

    abstract::Antineoplastic therapy with anthracyclines like doxorubicin (DOX) and daunorubicin (DNR) is limited by the possible development of a dose-related cardiomyopathy. Secondary alcohol metabolites like doxorubicinol (DOXol) and daunorubicinol (DNRol), formed by cytoplasmic two-electron reductases, have been implicated as p...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Silvestrini A,Meucci E,Vitali A,Giardina B,Mordente A

    更新日期:2006-11-01 00:00:00

  • Cytochrome P450 2A-catalyzed metabolic activation of structurally similar carcinogenic nitrosamines: N'-nitrosonornicotine enantiomers, N-nitrosopiperidine, and N-nitrosopyrrolidine.

    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


    authors: Wong HL,Murphy SE,Hecht SS

    更新日期:2005-01-01 00:00:00

  • Discovery of carboxyethylpyrroles (CEPs): critical insights into AMD, autism, cancer, and wound healing from basic research on the chemistry of oxidized phospholipids.

    abstract::Basic research, exploring the hypothesis that 2-(ω-carboxyethyl)pyrrole (CEP) modifications of proteins are generated nonenzymatically in vivo is delivering a bonanza of molecular mechanistic insights into age-related macular degeneration, autism, cancer, and wound healing. CEPs are produced through covalent modificat...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章,评审


    authors: Salomon RG,Hong L,Hollyfield JG

    更新日期:2011-11-21 00:00:00

  • Pristine (C60) and hydroxylated [C60(OH)24] fullerene phototoxicity towards HaCaT keratinocytes: type I vs type II mechanisms.

    abstract::The increasing use of fullerene nanomaterials has prompted widespread concern over their biological effects. Herein, we have studied the phototoxicity of gamma-cyclodextrin bicapped pristine C 60 [(gamma-CyD) 2/C 60] and its water-soluble derivative C 60(OH) 24 toward human keratinocytes. Our results demonstrated that...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Zhao B,He YY,Bilski PJ,Chignell CF

    更新日期:2008-05-01 00:00:00

  • Identification of antrocin from Antrodia camphorata as a selective and novel class of small molecule inhibitor of Akt/mTOR signaling in metastatic breast cancer MDA-MB-231 cells.

    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


    authors: Rao YK,Wu AT,Geethangili M,Huang MT,Chao WJ,Wu CH,Deng WP,Yeh CT,Tzeng YM

    更新日期:2011-02-18 00:00:00

  • Molecular cytotoxicity mechanisms of allyl alcohol (acrolein) in budding yeast.

    abstract::Allyl alcohol (AA) is one of the environmental pollutants used as a herbicide and industrial chemical. AA undergoes enzymatic oxidation in vivo to form Acrolein (Acr), a highly reactive and ubiquitous environmental toxicant. The exposure to AA/Acr has detrimental effects on cells and is highly fatal. In corroboration ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Golla U,Bandi G,Tomar RS

    更新日期:2015-06-15 00:00:00

  • Hplc/electrospray ionization mass spectrometric analysis of the heterocyclic aromatic amine carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in human milk.

    abstract::A new procedure has been developed for the extraction of 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and other heterocyclic aromatic amines from human breast milk samples. Extracts were analyzed by high-performance liquid chromatography/electrospray ionization/tandem mass spectrometry (HPLC/ESI-MS/MS) with...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Scott KA,Turesky RJ,Wainman BC,Josephy PD

    更新日期:2007-01-01 00:00:00

  • Chemoavailability of Organic Electrophiles: Impact of Hydrophobicity and Reactivity on Their Aquatic Excess Toxicity.

    abstract::Organic electrophiles have been recognized as important components of the exposome that can be characterized as cumulative totality of exposure in the organism in response to environmental perturbation. For such compounds, chemical reactivity may contribute significantly to the toxicological profile through covalent a...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Böhme A,Laqua A,Schüürmann G

    更新日期:2016-06-20 00:00:00