Arsenic exposure through drinking water is associated with longer telomeres in peripheral blood.

Abstract:

:Inorganic arsenic is a strong carcinogen, possibly by interaction with the telomere length. The aim of the study was to evaluate how chronic arsenic exposure from drinking water as well as the arsenic metabolism efficiency affect the individual telomere length and the expression of telomere-related genes. Two hundred two women with a wide range in exposure to arsenic via drinking water (3.5-200 μg/L) were recruited. Concentrations of arsenic metabolites in urine [inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA)] were measured. The relative telomere length in blood was measured by quantitative real-time polymerase chain reaction. Genotyping (N = 172) for eight SNPs in AS3MT and gene expression of telomere-related genes (in blood; N = 90) were performed. Urinary arsenic (sum of metabolites) was positively associated with telomere length (β = 0.65 × 10(-4), 95% CI = 0.031 × 10(-4)-1.3 × 10(-4), adjusted for age and BMI). Individuals with above median fractions of iAs and MMA showed significantly longer telomeres by increasing urinary arsenic (β = 1.0 × 10(-4), 95% CI = 0.21 × 10(-4)-1.8 × 10(-4) at high % iAs; β = 0.88 × 10(-4) 95% CI = 0.12 × 10(-4)-1.6 × 10(-4) at high % MMA) than those below the median (p = 0.80 and 0.44, respectively). Similarly, carriers of the slow and more toxic metabolizing AS3MT haplotype showed stronger positive associations between arsenic exposure and telomere length, as compared to noncarriers (interaction urinary arsenic and haplotype p = 0.025). Urinary arsenic was positively correlated with the expression of telomerase reverse transcriptase (TERT, Spearman r = 0.22, p = 0.037), but no association was found between TERT expression and telomere length. Arsenic in drinking water influences the telomere length, and this may be a mechanism for its carcinogenicity. A faster and less toxic arsenic metabolism diminishes arsenic-related telomere elongation.

journal_name

Chem Res Toxicol

authors

Li H,Engström K,Vahter M,Broberg K

doi

10.1021/tx300222t

subject

Has Abstract

pub_date

2012-11-19 00:00:00

pages

2333-9

issue

11

eissn

0893-228X

issn

1520-5010

journal_volume

25

pub_type

杂志文章
  • Biomarkers of furan exposure by metabolic profiling of rat urine with liquid chromatography-tandem mass spectrometry and principal component analysis.

    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

    authors: Kellert M,Wagner S,Lutz U,Lutz WK

    更新日期:2008-03-01 00:00:00

  • Water-soluble organotellurium compounds: catalytic protection against peroxynitrite and release of zinc from metallothionein.

    abstract::The antioxidant properties of a number of water-soluble diorganyl tellurides have been investigated. These organotellurium compounds efficiently protect against peroxynitrite-mediated oxidation of dihydrorhodamine 123, hydroxylation of benzoate, and nitration of 4-hydroxyphenyl acetate. The peroxidation of the zinc st...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx990156g

    authors: Jacob C,Arteel GE,Kanda T,Engman L,Sies H

    更新日期:2000-01-01 00:00:00

  • Redox properties and activity of iron-citrate complexes: evidence for redox cycling.

    abstract::Iron in iron overload disease is present as non-transferrin-bound iron, consisting of iron, citrate, and albumin. We investigated the redox properties of iron citrate by electrochemistry, by the kinetics of its reaction with ascorbate, by ESR, and by analyzing the products of reactions of ascorbate with iron citrate c...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx500377b

    authors: Adam FI,Bounds PL,Kissner R,Koppenol WH

    更新日期:2015-04-20 00:00:00

  • Oxidative bioactivation of abacavir in subcellular fractions of human antigen presenting cells.

    abstract::Human exposure to abacavir, a primary alcohol antiretroviral, is associated with the development of immunological drug reactions in individuals carrying the HLA risk allele B*57:01. Interaction of abacavir with antigen presenting cells results in cell activation through an Hsp70-mediated Toll-like receptor pathway and...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx400041v

    authors: Bell CC,Santoyo Castelazo A,Yang EL,Maggs JL,Jenkins RE,Tugwood J,O'Neill PM,Naisbitt DJ,Park BK

    更新日期:2013-07-15 00:00:00

  • A Novel Lipidomics-Based Approach to Evaluating the Risk of Clinical Hepatotoxicity Potential of Drugs in 3D Human Microtissues.

    abstract::The importance of adsorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis is expected to grow substantially due to recent failures in detecting severe toxicity issues of new chemical entities during preclinical/clinical development. Traditionally, safety risk assessment studies for humans have b...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.9b00364

    authors: Goracci L,Valeri A,Sciabola S,Aleo MD,Moritz W,Lichtenberg J,Cruciani G

    更新日期:2020-01-21 00:00:00

  • Distinct endoplasmic reticulum signaling pathways regulate apoptotic and necrotic cell death following iodoacetamide treatment.

    abstract::Environmental stress induces the synthesis of glucose-regulated proteins (Grps) in the endoplasmic reticulum (ER) and heat shock proteins (Hsps) in the cytoplasm. Iodoacetamide (IDAM), a prototypical alkyating agent, induces both Grp and Hsp synthesis in renal epithelial cells and causes necrosis which is prevented by...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx990054q

    authors: van De Water B,Wang Y,Asmellash S,Liu H,Zhan Y,Miller E,Stevens JL

    更新日期:1999-10-01 00:00:00

  • Heterocyclic derivatives of 3-substituted-1,1,1-trifluoro-2-propanones as inhibitors of esterolytic enzymes.

    abstract::A series of (alkylthio)trifluoropropanones containing a heterocyclic moiety was synthesized. The compounds were tested for in vitro inhibition of four hydrolytic enzymes including insect juvenile hormone esterase (JHE), eel acetylcholinesterase (AChE), yeast lipase (LP), and bovine alpha-chymotrypsin. The I50 values r...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00016a009

    authors: Székács A,Halarnkar PP,Olmstead MM,Prag KA,Hammock BD

    更新日期:1990-07-01 00:00:00

  • Excision of a lyase-resistant oxidized abasic lesion from DNA.

    abstract::The C2'-oxidized abasic lesion (C2-AP) is produced in DNA that is subjected to oxidative stress. The lesion disrupts replication and gives rise to mutations that are dependent upon the identity of the upstream nucleotide. Ape1 incises C2-AP, but the 5'-phosphorylated fragment is not a substrate for the lyase activity ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx9003984

    authors: Wong RS,Sczepanski JT,Greenberg MM

    更新日期:2010-04-19 00:00:00

  • Identification of drug-induced myocardial infarction-related protein targets through the prediction of drug-target interactions and analysis of biological processes.

    abstract::Drug-induced myocardial infarction (DIMI) is one of the most serious adverse drug effects that often lead to death. Therefore, the identification of DIMI at the early stages of drug development is essential. For this purpose, the in vitro testing and in silico prediction of interactions between drug-like substances an...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx500147d

    authors: Ivanov SM,Lagunin AA,Pogodin PV,Filimonov DA,Poroikov VV

    更新日期:2014-07-21 00:00:00

  • Regioisomeric synthesis and characteristics of the alpha-hydroxy-1,N(2)-propanodeoxyguanosine.

    abstract::Acrolein, a known mutagen, undergoes reaction in vitro under physiological conditions with both 2'-deoxyguanosine and native DNA to give rise to exocyclic adducts of the 5,6,7,8-tetrahydropyrimido[1,2-a]purine-10(3H)-one class having a hydroxyl group at either the 6 or the 8 position (these positions are respectively ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx015568f

    authors: Huang Y,Johnson F

    更新日期:2002-02-01 00:00:00

  • Identification of 14 quercetin phase II mono- and mixed conjugates and their formation by rat and human phase II in vitro model systems.

    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

    authors: van der Woude H,Boersma MG,Vervoort J,Rietjens IM

    更新日期:2004-11-01 00:00:00

  • Covalent binding of penicillamine to macrophages: implications for penicillamine-induced autoimmunity.

    abstract::Idiosyncratic drug reactions (IDRs) represent a major clinical problem, and at present, the mechanisms involved are still poorly understood. One animal model that we have used for mechanistic studies of IDRs is penicillamine-induced autoimmunity in Brown Norway (BN) rats. Previous work in our lab found that macrophage...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx900087z

    authors: Li J,Mannargudi B,Uetrecht JP

    更新日期:2009-07-01 00:00:00

  • Toxic metabolite formation from Troglitazone (TGZ): new insights from a DFT study.

    abstract::The hepatotoxicity of Troglitazone (TGZ) has been ascribed to the formation of reactive metabolites, and the primary reactive metabolite of TGZ has been confirmed to be an o-quinone methide. Oxidation of the chromane moiety is also known to produce quinone containing metabolites. Quantum chemical studies have been per...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx200110h

    authors: Dixit VA,Bharatam PV

    更新日期:2011-07-18 00:00:00

  • No role of homologous recombination in dealing with β-lapachone cytotoxicity in yeast.

    abstract::β-Lapachone (β-lap) is a promising antitumoral agent. DNA base oxidation and alkylation are among the expected damages by β-lap. Herein, we have explored the role that the homologous recombination pathway (HR), a critical DNA repair process in Saccharomyces cerevisiae, has in the cytotoxic profile of β-lap. We have fu...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx2004618

    authors: Quevedo O,García-Luis J,Lorenzo-Castrillejo I,Machín F

    更新日期:2011-12-19 00:00:00

  • Globin monoadducts and cross-links provide evidence for the presence of S-(1,2-dichlorovinyl)-L-cysteine sulfoxide, chlorothioketene, and 2-chlorothionoacetyl chloride in the circulation in rats administered S-(1,2-dichlorovinyl)-L-cysteine.

    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

    authors: Barshteyn N,Elfarra AA

    更新日期:2009-09-01 00:00:00

  • Inactivation of rat hepatic cytochrome P-450 isozymes by 3,5-dicarbethoxy- 2,6-dimethyl-4-ethyl-1,4-dihydropyridine.

    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

    authors: Sugiyama K,Yao K,Rettie AE,Correia MA

    更新日期:1989-11-01 00:00:00

  • Identification and characterization of thiosemicarbazones with antifungal and antitumor effects: cellular iron chelation mediating cytotoxic activity.

    abstract::Thiosemicarbazones derived from acetylpyrazines were prepared by condensing an acetylpyrazine or a ring-substituted acetylpyrazine with thiosemicarbazide. Using the same procedure, N, N-dimethylthiosemicarbazones were synthesized from acetylpyrazines and N, N-dimethylthiosemicarbazide. A total of 20 compounds (16 nove...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx800182k

    authors: Opletalová V,Kalinowski DS,Vejsová M,Kunes J,Pour M,Jampílek J,Buchta V,Richardson DR

    更新日期:2008-09-01 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

    doi:10.1021/tx100318m

    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

  • Structure-toxicity relationships for the effects to Tetrahymena pyriformis of aliphatic, carbonyl-containing, alpha,beta-unsaturated chemicals.

    abstract::Toxicity data for 82 aliphatic chemicals with an alpha,beta-unsaturated substructure were compiled. Toxicity was assessed in the 2-day Tetrahymena pyriformis population growth impairment assay. Toxic potency [log(IGC50(-1))] for most of these chemicals was in excess of baseline narcosis as quantified by the 1-octanol/...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx049833j

    authors: Schultz TW,Netzeva TI,Roberts DW,Cronin MT

    更新日期:2005-02-01 00:00:00

  • Synthesis, microsome-mediated metabolism, and identification of major metabolites of environmental pollutant naphtho[8,1,2-ghi]chrysene.

    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

    authors: Sharma AK,Gowdahalli K,Gimbor M,Amin S

    更新日期:2008-05-01 00:00:00

  • Genotoxicity of the hydroquinone metabolite of ochratoxin A: structure-activity relationships for covalent DNA adduction.

    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

    authors: Tozlovanu M,Faucet-Marquis V,Pfohl-Leszkowicz A,Manderville RA

    更新日期:2006-09-01 00:00:00

  • Reduction of dimethylarsinic acid to the highly toxic dimethylarsinous acid by rats and rat liver cytosol.

    abstract::Dimethylarsinic acid (DMAs(V)), the major urinary metabolite of inorganic arsenic, is weakly cytotoxic, whereas its reduced form, dimethylarsinous acid (DMAs(III)), is highly toxic. Although glutathione S-transferase omega 1 (GSTO1) and arsenic methyltransferase have been shown or thought to catalyze DMAs(V) reduction...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx300505v

    authors: Németi B,Gregus Z

    更新日期:2013-03-18 00:00:00

  • Mechanism of formation of ethenoguanine adducts from 2-haloacetaldehydes: 13C-labeling patterns with 2-bromoacetaldehyde.

    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

    authors: Guengerich FP,Persmark M

    更新日期:1994-03-01 00:00:00

  • Microprobe X-ray absorption spectroscopic determination of the oxidation state of intracellular chromium following exposure of V79 Chinese hamster lung cells to genotoxic chromium complexes.

    abstract::The oxidation state of intracellular chromium has been determined directly in mammalian lung cells exposed to mutagenic and carcinogenic chromium compounds. Microprobe X-ray absorption spectroscopy (XAS) experiments on single V79 Chinese hamster lung cells showed that Cr(VI) and Cr(V) complexes were reduced completely...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx970010m

    authors: Dillon CT,Lay PA,Cholewa M,Legge GJ,Bonin AM,Collins TJ,Kostka KL,Shea-McCarthy G

    更新日期:1997-05-01 00:00:00

  • Action-at-a-distance mutagenesis induced by oxidized guanine in Werner syndrome protein-reduced human cells.

    abstract::8-Oxo-7,8-dihydroguanine (G(O), 8-hydroxyguanine) in DNA is one of the most important oxidatively damaged bases and causes G:C → T:A substitution mutations. The Werner syndrome protein (WRN) is a cancer-related RecQ DNA helicase and plays many roles in DNA replication and repair. To examine the relationships between G...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx500418m

    authors: Kamiya H,Yamazaki D,Nakamura E,Makino T,Kobayashi M,Matsuoka I,Harashima H

    更新日期:2015-04-20 00:00:00

  • 16α-Hydroxyestrone: Mass Spectrometry-Based Methodologies for the Identification of Covalent Adducts Formed with Blood Proteins.

    abstract::Elevated levels of the estrone metabolite, 16α-hydroxyestrone (16αOHE1), have been linked with multiple diseases. As an electrophilic reactive metabolite, covalent binding to proteins is thought to constitute one of the possible mechanisms in the onset of deleterious health outcomes associated with 16αOHE1. Whereas ma...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.0c00171

    authors: Charneira C,Nunes J,Antunes AMM

    更新日期:2020-08-17 00:00:00

  • Cyclooxygenase-2 expression is up-regulated by 2-aminobiphenyl in a ROS and MAPK-dependent signaling pathway in a bladder cancer cell line.

    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

    authors: Chen CC,Cheng YY,Chen SC,Tuan YF,Chen YJ,Chen CY,Chen LC

    更新日期:2012-03-19 00:00:00

  • Common E-Cigarette Flavoring Chemicals Impair Neutrophil Phagocytosis and Oxidative Burst.

    abstract::E-cigarette flavorings have not been thoroughly evaluated for inhalational toxicity. We have shown that the flavoring chemical cinnamaldehyde impairs human neutrophils, macrophages, and natural killer cells. Here we investigated the effects of other common e-liquid flavoring chemicals on phagocytosis and oxidative bur...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.9b00171

    authors: Hickman E,Herrera CA,Jaspers I

    更新日期:2019-06-17 00:00:00

  • The Fenton degradation as a nonenzymatic model for microsomal denitrosation of N-nitrosodimethylamine.

    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

    authors: Heur YH,Streeter AJ,Nims RW,Keefer LK

    更新日期:1989-07-01 00:00:00

  • Chemical modification of lysozyme, glucose 6-phosphate dehydrogenase, and bovine eye lens proteins induced by peroxyl radicals: role of oxidizable amino acid residues.

    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

    authors: Arenas A,López-Alarcón C,Kogan M,Lissi E,Davies MJ,Silva E

    更新日期:2013-01-18 00:00:00