Highly Predictive Reprogramming of tRNA Modifications Is Linked to Selective Expression of Codon-Biased Genes.


:Cells respond to stress by controlling gene expression at several levels, with little known about the role of translation. Here, we demonstrate a coordinated translational stress response system involving stress-specific reprogramming of tRNA wobble modifications that leads to selective translation of codon-biased mRNAs representing different classes of critical response proteins. In budding yeast exposed to four oxidants and five alkylating agents, tRNA modification patterns accurately distinguished among chemically similar stressors, with 14 modified ribonucleosides forming the basis for a data-driven model that predicts toxicant chemistry with >80% sensitivity and specificity. tRNA modification subpatterns also distinguish SN1 from SN2 alkylating agents, with SN2-induced increases in m(3)C in tRNA mechanistically linked to selective translation of threonine-rich membrane proteins from genes enriched with ACC and ACT degenerate codons for threonine. These results establish tRNA modifications as predictive biomarkers of exposure and illustrate a novel regulatory mechanism for translational control of cell stress response.


Chem Res Toxicol


Chan CT,Deng W,Li F,DeMott MS,Babu IR,Begley TJ,Dedon PC




Has Abstract


2015-05-18 00:00:00












  • Identification of colchicine in placental blood from patients using herbal medicines.

    abstract::While characterizing natural antiinflammatory substances in human placental blood, we discovered a factor that affected human neutrophils and their adherence. Rigorous chemical and stereochemical analyses revealed this factor to be the well-known alkaloid, colchicine. When samples from individual patients were analyze...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Petty HR,Fernando M,Kindzelskii AL,Zarewych BN,Ksebati MB,Hryhorczuk LM,Mobashery S

    更新日期:2001-09-01 00:00:00

  • Cytotoxicity of calcium rectorite micro/nanoparticles before and after organic modification.

    abstract::Organically modified rectorite (OREC) micro/nanoparticles can be synthesized by organic modification from calcium rectorite (Ca(2+)-REC or REC), a common form of rectorite in nature. Although REC and OREC have potential applications in food packing and drug delivery, their cytotoxicity is not clear. In the present stu...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Liu Y,Deng H,Xiao C,Xie C,Zhou X

    更新日期:2014-08-18 00:00:00

  • Cyclic imines: chemistry and mechanism of action: a review.

    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


    authors: Otero A,Chapela MJ,Atanassova M,Vieites JM,Cabado AG

    更新日期:2011-11-21 00:00:00

  • Quantitative component analysis of mixtures for risk assessment: application to eye irritation.

    abstract::A methodology called quantitative component analysis of mixtures (QCAM) was used to analyze an existing set of product formulation data to determine if the irritating ingredients in the mixtures could be identified. Eye irritation scores, based on a rat model, for 18 mixtures having a composite total of 37 components,...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Patel HC,Duca JS,Hopfinger AJ,Glendening CD,Thompson ED

    更新日期:1999-11-01 00:00:00

  • Synthesis and mutagenicity of trans-dihydrodiol metabolites of benzo[b]naphtho[2,1-d]thiophene.

    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


    authors: Misra B,Amin S

    更新日期:1990-03-01 00:00:00

  • Influence of glutathione and glutathione S-transferases on DNA interstrand cross-link formation by 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine, the active anticancer moiety generated by laromustine.

    abstract::Prodrugs of 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine (90CE) are promising anticancer agents. The 90CE moiety is a readily latentiated, short-lived (t1/2 ∼ 30 s) chloroethylating agent that can generate high yields of oxophilic electrophiles responsible for the chloroethylation of the O-6 position of guanine ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Penketh PG,Patridge E,Shyam K,Baumann RP,Zhu R,Ishiguro K,Sartorelli AC

    更新日期:2014-08-18 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


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

    更新日期:2014-07-21 00:00:00

  • The design of agents to control DNA methylation adducts. Enhanced major groove methylation of DNA by an N-methyl-N-nitrosourea functionalized phenyl neutral red intercalator.

    abstract::An N-methyl-N-nitrosourea (MNU) moiety [CH3N(N=O)C(=O)NH-] linked to the C4'-position of the 5-substituted phenyl ring of phenyl neutral red (PNR), 2-methyl-3-amino-5-[p-[[2-[(N-nitroso-N-methylcarbamoyl)amino]ethy l] carbamoyl]phenyl]-7-(dimethylamino)phenazenium chloride (MNU-PNR), has been synthesized as an approac...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Mehta P,Church K,Williams J,Chen FX,Encell L,Shuker DE,Gold B

    更新日期:1996-09-01 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

  • Comparison of crystal structure and theory for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

    abstract::The crystal structure of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) has been determined by single-crystal X-ray crystallography. Crystals grown by evaporation of an aqueous solution form in the monoclinic space group P2(1)/n with two molecules of PhIP per asymmetric unit, along with six w...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Parkin S,Marsch GA,Hope H,Whitney E,Winter NW,Colvin ME,Felton JS,Turteltaub KW

    更新日期:1996-04-01 00:00:00

  • Formation of deoxyguanosine cross-links from calf thymus DNA treated with acrolein and 4-hydroxy-2-nonenal.

    abstract::Acrolein (AC) and 4-hydroxy-2-nonenal (HNE) are endogenous bis-electrophiles that arise from the oxidation of polyunsaturated fatty acids. AC is also found in high concentrations in cigarette smoke and automobile exhaust. These reactive α,β-unsaturated aldehyde (enal) covalently modify nucleic acids, to form exocyclic...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Kozekov ID,Turesky RJ,Alas GR,Harris CM,Harris TM,Rizzo CJ

    更新日期:2010-11-15 00:00:00

  • Comparative Toxicogenomic Responses to the Flame Retardant mITP in Developing Zebrafish.

    abstract::Monosubstituted isopropylated triaryl phosphate (mITP) is a major component of Firemaster 550, an additive flame retardant mixture commonly used in polyurethane foams. Developmental toxicity studies in zebrafish established mITP as the most toxic component of FM 550, which causes pericardial edema and heart looping fa...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Haggard DE,Das SR,Tanguay RL

    更新日期:2017-02-20 00:00:00

  • Epoxide ring opening and related reactivities of cyclopenta polycyclic aromatic hydrocarbons: quantum mechanical studies.

    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 A...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Rabinowitz JR,Little SB

    更新日期:1992-03-01 00:00:00

  • Benzo[a]pyrene diol epoxide forms covalent adducts with deoxycytidylic acid by alkylation at both exocyclic amino N(4) and ring imino N-3 positions.

    abstract::The carcinogen 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) alkylates DNA at dGuo, dAdo, and dCyd. dCyd adducts, formed in small amounts, elute near the more abundant dGuo adducts. We isolated the dCyd adducts formed with dCMP. Each BPDE enantiomer forms three major adducts with dCMP, two...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Wolfe AR,Smith TJ,Meehan T

    更新日期:2004-04-01 00:00:00

  • Peroxynitrite-dependent tryptophan nitration.

    abstract::Peroxynitrite (ONOO-), the reaction product of superoxide (O2.-) and nitric oxide (.NO), nitrates tyrosine and other phenolics. We report herein that tryptophan is also nitrated by peroxynitrite in the absence of transition metals to one predominant isomer of nitrotryptophan, as determined from spectral characteristic...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Alvarez B,Rubbo H,Kirk M,Barnes S,Freeman BA,Radi R

    更新日期:1996-03-01 00:00:00

  • Surface modification of quartz inhibits toxicity, particle uptake, and oxidative DNA damage in human lung epithelial cells.

    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


    authors: Schins RP,Duffin R,Höhr D,Knaapen AM,Shi T,Weishaupt C,Stone V,Donaldson K,Borm PJ

    更新日期:2002-09-01 00:00:00

  • Human glutathione transferases catalyzing the conjugation of the hepatoxin microcystin-LR.

    abstract::Many cyanobacterial species are able to produce cyanotoxins as secondary metabolites. Among them, microcystins (MC) are a group of around 80 congeners of toxic cyclic heptapeptides. MC-LR is the most studied MC congener, in view of its high acute hepatotoxicity and tumor promoting activity. Humans may be exposed to cy...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Buratti FM,Scardala S,Funari E,Testai E

    更新日期:2011-06-20 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

  • Profiling the reactive metabolites of xenobiotics using metabolomic technologies.

    abstract::A predominant pathway of xenobiotic-induced toxicity is initiated by bioactivation. Characterizing reactive intermediates will provide information on the structure of reactive species, thereby defining a potential bioactivation mechanism. Because most reactive metabolites are not stable, it is difficult to detect them...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Li F,Lu J,Ma X

    更新日期:2011-05-16 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


    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

  • Molecular Signatures Associated with Treatment of Triple-Negative MDA-MB231 Breast Cancer Cells with Histone Deacetylase Inhibitors JAHA and SAHA.

    abstract::Jay Amin hydroxamic acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA's cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Librizzi M,Caradonna F,Cruciata I,Dębski J,Sansook S,Dadlez M,Spencer J,Luparello C

    更新日期:2017-12-18 00:00:00

  • Increased levels of inosine in a mouse model of inflammation.

    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

    pub_type: 杂志文章


    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

  • Oxidation of N-hydroxynorzimeldine to a stable nitrone by hepatic monooxygenases.

    abstract::Liver microsomes from uninduced hogs catalyzed the NADPH-dependent N-oxidation of the hydroxylamine (Z)-3-(4-bromophenyl)-N-hydroxy-N-methyl-3-(3-pyridyl)allylamine. The conjugated nitrone N-[(2Z)-3-(4-bromophenyl)-3-(3-pyridyl)-2-propenylidene]methylamin e N-oxide was the principal product and accounted for 90-95% of...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Cashman JR,Yang ZC,Högberg T

    更新日期:1990-09-01 00:00:00

  • Isoprene-Derived Secondary Organic Aerosol Induces the Expression of MicroRNAs Associated with Inflammatory/Oxidative Stress Response in Lung Cells.

    abstract::Exposure to fine particulate matter (PM2.5), of which secondary organic aerosol (SOA) is a major constituent, is linked to adverse health outcomes, including cardiovascular disease, lung cancer, and preterm birth. Atmospheric oxidation of isoprene, the most abundant nonmethane hydrocarbon emitted into Earth's atmosphe...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Eaves LA,Smeester L,Hartwell HJ,Lin YH,Arashiro M,Zhang Z,Gold A,Surratt JD,Fry RC

    更新日期:2020-02-17 00:00:00

  • Structure-activity relationships for contact allergenic potential of gamma,gamma-dimethyl-gamma-butyrolactone derivatives. 1. Synthesis and electrophilic reactivity studies of alpha-(omega-substituted-alkyl)-gamma,gamma-dimethyl-gamma-butyrolacton es and

    abstract::A series of alpha-(X-substituted-methyl)-gamma,gamma-dimethyl-gamma-butyrolactones (series 1), a series of alpha-(2-X-substituted-ethyl)-gamma,gamma-dimethyl-gamma-butyrolactones (series 2), where X is a leaving group, and the compound alpha-(3-bromopropyl)-gamma,gamma-butyrolactone (3) were synthesized. Their reactio...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Franot C,Roberts DW,Smith RG,Basketter DA,Benezra C,Lepoittevin JP

    更新日期:1994-05-01 00:00:00

  • Complexation of arsenic species in rabbit erythrocytes.

    abstract::The binding of arsenite, As(III), and arsenate, As(V), by molecules in the intracellular compartment of rabbit erythrocytes has been studied by 1H- and 31P-NMR spectroscopy, uptake of 73As, and ultrafiltration experiments. For intact erythrocytes to which 0.1-0.4 mM arsenite was added, direct evidence was obtained for...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Delnomdedieu M,Basti MM,Styblo M,Otvos JD,Thomas DJ

    更新日期:1994-09-01 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


    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

  • Role of quinones in toxicology.

    abstract::Quinones represent a class of toxicological intermediates which can create a variety of hazardous effects in vivo, including acute cytotoxicity, immunotoxicity, and carcinogenesis. The mechanisms by which quinones cause these effects can be quite complex. Quinones are Michael acceptors, and cellular damage can occur t...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章,评审


    authors: Bolton JL,Trush MA,Penning TM,Dryhurst G,Monks TJ

    更新日期:2000-03-01 00:00:00

  • Enzymatic reduction of 3-nitrotyrosine generates superoxide.

    abstract::Spin-trapping with 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) was used to demonstrate that 3-nitrotyrosine (nitrotyrosine) promotes the formation of substantial amounts of reactive oxygen species (O2.- and *OH), when incubated with NAD(H)-cytochrome c reductase and a corresponding electron donor. Spin adduct formation is...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Krainev AG,Williams TD,Bigelow DJ

    更新日期:1998-05-01 00:00:00

  • Oxidation of aflatoxins and sterigmatocystin by human liver microsomes: significance of aflatoxin Q1 as a detoxication product of aflatoxin B1.

    abstract::Aflatoxin Q1 8,9-oxide was synthesized and found to yield lower levels of N7-guanyl adducts than obtained from aflatoxin B1 8,9-oxide when mixed with calf thymus DNA or Salmonella typhimurium TA 98 cells. However, when S. typhimurium TA 98 was treated with the (analogous) epoxides of aflatoxin B1, aflatoxin G1, aflato...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Raney KD,Shimada T,Kim DH,Groopman JD,Harris TM,Guengerich FP

    更新日期:1992-03-01 00:00:00