abstract：:Exposure to arsenic affects large human populations worldwide and has been associated with a long list of human diseases, including skin, bladder, lung, and liver cancers, diabetes, and cardiovascular disorders. In addition, there are large individual differences in susceptibility to arsenic-induced diseases, which ar...

journal_title：Chemical research in toxicology

authors： Lu K,Cable PH,Abo RP,Ru H,Graffam ME,Schlieper KA,Parry NM,Levine S,Bodnar WM,Wishnok JS,Styblo M,Swenberg JA,Fox JG,Tannenbaum SR

更新日期：2013-12-16 00:00:00

abstract：:Cyclic imides are known for their antitumor activity, especially the naphthalimide derivatives, such as Mitonafide and Amonafide. Recently, we have demonstrated the cytotoxic effect of a series of naphthalimide derivatives against B16F10 melanoma cells. On the basis of this fact, we have developed a study starting fro...

journal_title：Chemical research in toxicology

authors： Machado KE,de Oliveira KN,Andreossi HM,Bubniak Ldos S,de Moraes AC,Gaspar PC,Andrade Eda S,Nunes RJ,Santos-Silva MC

更新日期：2013-12-16 00:00:00

abstract：:Idiosyncratic adverse drug reactions due to the anti-inflammatory drug diclofenac have been proposed to be caused by the generation of reactive acyl glucuronides and oxidative metabolites. For the oxidative metabolism of diclofenac by cytochromes P450 at least five different reactive intermediates have been proposed p...

journal_title：Chemical research in toxicology

authors： Dragovic S,Boerma JS,Vermeulen NP,Commandeur JN

更新日期：2013-11-18 00:00:00

abstract：:Mouse models are powerful tools to study the developmental neurotoxicity of polychlorinated biphenyls (PCBs); however, studies of the oxidation of chiral PCB congeners to potentially neurotoxic hydroxylated metabolites (OH-PCBs) in mice have not been reported. Here, we investigate the atropselective oxidation of chira...

journal_title：Chemical research in toxicology

authors： Wu X,Duffel M,Lehmler HJ

更新日期：2013-11-18 00:00:00

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

authors： van Midwoud PM,Sturla SJ

更新日期：2013-11-18 00:00:00

abstract：:Hexavalent chromium is a human carcinogen activated primarily by direct reduction with cellular ascorbate and to a lesser extent, by glutathione. Cr(III), the final product of Cr(VI) reduction, forms six bonds allowing intermolecular cross-linking. In this work, we investigated the ability of Cr(VI) to cause interstra...

journal_title：Chemical research in toxicology

authors： Morse JL,Luczak MW,Zhitkovich A

更新日期：2013-10-21 00:00:00

abstract：:The major plant growth regulator ethephon degrades to ethylene and phosphate in aqueous solutions and plants and is spontaneously activated to a butyrylcholinesterase (BChE) inhibitor in alkaline solutions and animal tissues. In the present (31)P NMR kinetic study of the reactions of ethephon in pH 7.4 carbonate buffe...

journal_title：Chemical research in toxicology

authors： Lantz SR,Casida JE

更新日期：2013-09-16 00:00:00

abstract：:There is limited and sometimes contradictory information about the genotoxicity of the polycyclic aromatic hydrocarbon benzo[ghi]perylene (B[ghi]P). Using recently developed metabolic toxicity screening arrays and a biocolloid reactor-LC-MS/MS approach, both featuring films of DNA and human metabolic enzymes, we demon...

journal_title：Chemical research in toxicology

authors： Pan S,Li D,Zhao L,Schenkman JB,Rusling JF

更新日期：2013-08-19 00:00:00

abstract：:Topoisomerase II regulates DNA topology by generating transient double-stranded breaks. The anticancer drug etoposide targets topoisomerase II and is associated with the formation of secondary leukemias in patients. The quinone and catechol metabolites of etoposide may contribute to strand breaks that trigger leukemic...

journal_title：Chemical research in toxicology

authors： Jacob DA,Gibson EG,Mercer SL,Deweese JE

更新日期：2013-08-19 00:00:00

abstract：:Aminoglutethimide (AMG) is an aromatic amine aromatase inhibitor associated with a high incidence of idiosyncratic blood dyscrasias, especially agranulocytosis. Animal models of idiosyncratic drug reactions (IDRs) represent essential tools to study these reactions; however, there is currently no valid model of idiosyn...

journal_title：Chemical research in toxicology

authors： Ng W,Uetrecht J

更新日期：2013-08-19 00:00:00

abstract：:While xenobiotic carboxylic acids (XCAs) have been studied extensively with respect to their enzymatic conversion to potentially reactive acyl glucuronides with implications to drug induced hepatotoxicity, the formation of xenobiotic-S-acyl-CoA thioesters (xenobiotic-CoAs) have been much less studied in spite of data ...

journal_title：Chemical research in toxicology

authors： Darnell M,Weidolf L

更新日期：2013-08-19 00:00:00

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

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

abstract：:The crystal structure of Rad4/Rad23, the yeast homolog of the human nucleotide excision repair (NER) lesion recognition factor XPC-RAD23B ( Min , J. H. and Pavletich , N. P. ( 2007 ) Nature 449 , 570 - 575 ) reveals that the lesion-partner base is flipped out of the helix and binds to amino acids of the protein. This ...

journal_title：Chemical research in toxicology

authors： Cai Y,Zheng H,Ding S,Kropachev K,Schwaid AG,Tang Y,Mu H,Wang S,Geacintov NE,Zhang Y,Broyde S

更新日期：2013-07-15 00:00:00

abstract：:The synthesis, toxicity, neuroprotection, and human acetylcholinesterase (hAChE)/ human butyrylcholinesterase (hBuChE) inhibition properties of β-naphthotacrines1-14 as new drugs for Alzheimer's disease (AD) potential treatment, are reported. β-Naphthotacrines1-14 showed lower toxicity than tacrine; moreover, at the h...

journal_title：Chemical research in toxicology

authors： Esquivias-Pérez M,Maalej E,Romero A,Chabchoub F,Samadi A,Marco-Contelles J,Oset-Gasque MJ

更新日期：2013-06-17 00:00:00

abstract：:Nevirapine (NVP) treatment is associated with a significant incidence of skin rash in humans, and it also causes a similar immune-mediated skin rash in Brown Norway (BN) rats. We have shown that the sulfate of a major oxidative metabolite, 12-OH-NVP, covalently binds in the skin. The fact that the sulfate metabolite i...

journal_title：Chemical research in toxicology

authors： Sharma AM,Novalen M,Tanino T,Uetrecht JP

更新日期：2013-05-20 00:00:00

abstract：:Concerns have been raised that diacetyl (DA) might be a respiratory sensitizer based on its LUMO energy similar to that of the respiratory allergen toluene-2,4-diisocyanate (TDI) and results of a local lymph node assay (LLNA) that reported an EC3 of 1.9%. To better understand the concerns, we performed a systematic li...

journal_title：Chemical research in toxicology

authors： Dworak JJ,Roberts DW,Calter MA,Fields CA,Borak J

更新日期：2013-05-20 00:00:00

abstract：:One possible mechanism linking inflammation with cancer involves the generation of reactive oxygen, nitrogen, and halogen species by activated macrophages and neutrophils infiltrating sites of infection or tissue damage, with these chemical mediators causing damage that ultimately leads to cell death and mutation. To ...

journal_title：Chemical research in toxicology

authors： Prestwich EG,Mangerich A,Pang B,McFaline JL,Lonkar P,Sullivan MR,Trudel LJ,Taghizedeh K,Dedon PC

更新日期：2013-04-15 00:00:00

abstract：:Bisphenol A (BPA) is used in the production of polycarbonate plastics and epoxy resins for baby bottles, liners of canned food, and many other consumer products. Previously, BPA has been shown to reduce the activity of several antioxidant enzymes, which may contribute to oxidative stress. However, the underlying mecha...

journal_title：Chemical research in toxicology

authors： Chepelev NL,Enikanolaiye MI,Chepelev LL,Almohaisen A,Chen Q,Scoggan KA,Coughlan MC,Cao XL,Jin X,Willmore WG

更新日期：2013-03-18 00:00:00

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

authors： Németi B,Gregus Z

更新日期：2013-03-18 00:00:00

abstract：:The trichothecene mycotoxin T-2 toxin, which is produced by fungi of the Fusarium species, is a worldwide occurring contaminant of cereal based food and feed. The cytotoxic properties of T-2 toxin are already well described with apoptosis being a major mechanism of action in various cell lines as well as in primary ce...

journal_title：Chemical research in toxicology

authors： Weidner M,Lenczyk M,Schwerdt G,Gekle M,Humpf HU

更新日期：2013-03-18 00:00:00

abstract：:So far, there is limited information on biotransformation mechanisms and products of polar contaminants in freshwater crustaceans. In the present study, metabolites of biocides and pharmaceuticals formed in Gammarus pulex and Daphnia magna were identified using liquid chromatography-high resolution mass spectrometry. ...

journal_title：Chemical research in toxicology

authors： Jeon J,Kurth D,Hollender J

更新日期：2013-03-18 00:00:00

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

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

更新日期：2013-01-18 00:00:00

abstract：:Quantitation of DNA adducts could provide critical information on the relationship between exposure to tobacco smoke and cancer risk in smokers. In this study, we developed a robust and sensitive liquid chromatography-tandem mass spectrometry method for the analysis of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasin...

journal_title：Chemical research in toxicology

authors： Stepanov I,Muzic J,Le CT,Sebero E,Villalta P,Ma B,Jensen J,Hatsukami D,Hecht SS

更新日期：2013-01-18 00:00:00

abstract：:Derivatives of methyl 3-(1-methyl-5-(1-methyl-5-(propylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl)-1H-pyrrol-3-ylamino)-3-oxopropane-1-sulfonate (1), a peptide-based DNA minor groove binding methylating agent, were synthesized and characterized. In all cases, the N-terminus was appended with an O-methyl sulfonate ester, while...

journal_title：Chemical research in toxicology

authors： Iyer P,Srinivasan A,Singh SK,Mascara GP,Zayitova S,Sidone B,Fouquerel E,Svilar D,Sobol RW,Bobola MS,Silber JR,Gold B

更新日期：2013-01-18 00:00:00

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 ...

journal_title：Chemical research in toxicology

authors： Li H,Engström K,Vahter M,Broberg K

更新日期：2012-11-19 00:00:00

abstract：:8-Oxo-2'-deoxyguanosine (OdG) is an abundant DNA lesion produced during oxidative damage to DNA. It can form relatively stable base pairs with both dC and dA that mimic natural dG:dC and dT:dA base pairs, respectively. Thus, when in the template strand, OdG can direct the insertion of either dCTP or dATP during replic...

journal_title：Chemical research in toxicology

authors： Hamm ML,Crowley KA,Ghio M,Lindell MA,McFadden EJ,Silberg JS,Weaver AM

更新日期：2012-11-19 00:00:00

abstract：:Nucleotide excision repair (NER) removes lesions caused by environmental mutagens or UV light from DNA. A hallmark of NER is the extraordinarily wide substrate specificity, raising the question of how one set of proteins is able to recognize structurally diverse lesions. Two key features of good NER substrates are tha...

journal_title：Chemical research in toxicology

authors： Yeo JE,Khoo A,Fagbemi AF,Schärer OD

更新日期：2012-11-19 00:00:00

abstract：:Drug-induced liver injury is the most common cause of market withdrawal of pharmaceuticals, and thus, there is considerable need for better prediction models for DILI early in drug discovery. We present a study involving 223 marketed drugs (51% associated with clinical hepatotoxicity; 49% non-hepatotoxic) to assess th...

journal_title：Chemical research in toxicology

authors： Sakatis MZ,Reese MJ,Harrell AW,Taylor MA,Baines IA,Chen L,Bloomer JC,Yang EY,Ellens HM,Ambroso JL,Lovatt CA,Ayrton AD,Clarke SE

更新日期：2012-10-15 00:00:00

abstract：:Skin sensitizers chemically modify skin proteins rendering them immunogenic. Sensitizing chemicals have been divided into applicability domains according to their suspected reaction mechanism. The widely accepted Schiff base applicability domain covers aldehydes and ketones, and detailed structure-activity-modeling fo...

journal_title：Chemical research in toxicology

authors： Natsch A,Gfeller H,Haupt T,Brunner G

更新日期：2012-10-15 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

authors： Chowdhury R,Godoy LC,Thiantanawat A,Trudel LJ,Deen WM,Wogan GN

更新日期：2012-10-15 00:00:00

abstract：:2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic aromatic amine that is formed during the cooking of meats. PhIP is a potential human carcinogen: it undergoes metabolic activation to form electrophilic metabolites that bind to DNA and proteins, including serum albumin (SA). The structures of Ph...

journal_title：Chemical research in toxicology

authors： Peng L,Dasari S,Tabb DL,Turesky RJ

更新日期：2012-10-15 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

authors： Hassuneh MR,Albini MA,Talib WH

更新日期：2012-10-15 00:00:00

abstract：:Cytochrome P450 2F1 (P450 2F1) is expressed exclusively in the human respiratory tract and is implicated in 3-methylindole (3MI)-induced pneumotoxicity via dehydrogenation of 3MI to a reactive electrophilic intermediate, 3-methyleneindolenine (3-MEI). Studies of P450 2F1 to date have been limited by the failure to exp...

journal_title：Chemical research in toxicology

authors： Behrendorff JB,Moore CD,Kim KH,Kim DH,Smith CA,Johnston WA,Yun CH,Yost GS,Gillam EM

更新日期：2012-09-17 00:00:00

abstract：:The formation of 8-oxo-7,8-dihydroguanine (G(O), 8-hydroxyguanine) in DNA and in the nucleotide pool results in G:C→T:A and A:T→C:G substitution mutations, respectively, since G(O) can pair with both C and A. In this study, the role of DNA polymerase κ in the mutagenicity of G(O) was investigated, using a supF shuttle...

journal_title：Chemical research in toxicology

authors： Kamiya H,Kurokawa M

更新日期：2012-08-20 00:00:00

abstract：:Reactive oxygen species (ROS), which can be produced during normal aerobic metabolism, can induce the formation of tandem DNA lesions, including 8,5'-cyclo-2'-deoxyadenosine (cyclo-dA) and 8,5'-cyclo-2'-deoxyguanosine (cyclo-dG). Previous studies have shown that cyclo-dA and cyclo-dG accumulate in cells and can block ...

journal_title：Chemical research in toxicology

authors： Swanson AL,Wang J,Wang Y

更新日期：2012-08-20 00:00:00

abstract：:1-{4-[(4-Phenyl-5-trifluoromethyl-2-thienyl)methoxy]benzyl}azetidine-3-carboxylic acid (MRL-A) is a potent sphingosine-1-phosphate-1 receptor agonist, with potential application as an immunosuppressant in organ transplantation or for the treatment of autoimmune diseases. When administered orally to rats, radiolabeled ...

journal_title：Chemical research in toxicology

authors： Aloysius H,Tong VW,Yabut J,Bradley SA,Shang J,Zou Y,Tschirret-Guth RA

更新日期：2012-07-16 00:00:00

abstract：:The toxicity of CuO nanoparticles (NPs) to human lung epithelial (A549) cells was investigated in this study. CuO NPs (10-100 mg/L) had significant toxicity to A549 cells, whereas CuO bulk particles (BPs) showed much lower toxicity (24 h IC(50), 58 and 15 mg/L for CuO BPs and NPs, respectively). Transmission electron ...

journal_title：Chemical research in toxicology

authors： Wang Z,Li N,Zhao J,White JC,Qu P,Xing B

更新日期：2012-07-16 00:00:00

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

authors： Vidaud C,Bourgeois D,Meyer D

更新日期：2012-06-18 00:00:00

abstract：:Nitric oxide (NO(•); nitrogen monoxide) is known to be a critical regulator of cell and tissue function through mechanisms that utilize its unique physicochemical properties as a small and uncharged free radical with limited reactivity. Here, the basic chemistry and biochemistry of NO(•) are summarized through the des...

journal_title：Chemical research in toxicology

authors： Toledo JC Jr,Augusto O

更新日期：2012-05-21 00:00:00

abstract：:Nanoparticles can reach the blood and cause inflammation, suggesting that nanoparticles-endothelial cells interactions may be pathogenically relevant. We evaluated the effect of titanium dioxide nanoparticles (TiO₂) on proliferation, death, and responses related with inflammatory processes such as monocytic adhesion a...

journal_title：Chemical research in toxicology

authors： Montiel-Dávalos A,Ventura-Gallegos JL,Alfaro-Moreno E,Soria-Castro E,García-Latorre E,Cabañas-Moreno JG,del Pilar Ramos-Godinez M,López-Marure R

更新日期：2012-04-16 00:00:00