Abstract：
:Hydrophobic and volatile chemicals have proven to be difficult to dose in cell assays. Cosolvents are often needed to dissolve these chemicals in cell culture medium. Moreover, the free concentration of these chemicals in culture medium may diminish over time due to metabolism, evaporation, and nonspecific binding to well plate surfaces and serum constituents. The aim of this study was to develop a partition-controlled dosing system to maintain constant concentrations of benzo(a)pyrene, 1,2-dichlorobenzene, and 1,2,4-trichlorobenzene in an ethoxyresorufin-O-deethylase (EROD) assay and a cytotoxicity assay with the rainbow trout (Oncorhynchus mykiss) cell lines RTL-W1 and RTgill-W1. Polydimethylsiloxane (PDMS) sheets were loaded with test chemicals in a spiked methanol/water solution and placed in the wells, filled with culture medium, of a 24-well culture plate. Cells were grown on inserts and were subsequently added to the wells with the PDMS sheets. The system reached equilibrium within 24 h, even for the very hydrophobic chemical benzo(a)pyrene. The reservoir of test chemical in PDMS was large enough to compensate for the loss of >95% of the test chemical from the culture medium. The PDMS sheets maintained medium concentrations constant for >72 h. Nominal median effect concentrations (EC(50)) were 1.3-7.0 times lower in the partition-controlled dosing systems than in conventional assays spiked using dimethyl sulfoxide (DMSO) as a carrier solvent, thus indicating that the apparent sensitivity of the bioassay increased when controlled and constant exposure conditions could be assured. The EC(50) values of the test chemicals based on free concentrations were estimated in the partition-controlled dosing systems using measured PDMS-bare culture medium partition coefficients. Results indicated that 61, 70, and 99.8% of 1,2-diclorobenzene, 1,2,4-trichlorobenzene, and benzo(a)pyrene were bound to serum constituents in the culture medium.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Kramer NI,Busser FJ,Oosterwijk MT,Schirmer K,Escher BI,Hermens JLdoi
10.1021/tx1002595subject
Has Abstractpub_date
2010-11-15 00:00:00pages
1806-14issue
11eissn
0893-228Xissn
1520-5010journal_volume
23pub_type
杂志文章abstract：:The primary products of one-electron oxidation of clozapine and olanzapine, very effective atypical antipsychotic drugs, have been spectroscopically characterized. The oxidation process has been studied under glassy matrix conditions and by a pulse radiolysis technique in aqueous solution. The rate constants for the o...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx700128c
更新日期：2007-08-01 00:00:00
abstract：:Faithful replication of DNA is a critical aspect in maintaining genome integrity. DNA polymerases are responsible for replicating DNA, and high-fidelity polymerases do this rapidly and at low error rates. Upon exposure to exogenous or endogenous substances, DNA can become damaged and this can alter the speed and fidel...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/acs.chemrestox.7b00224
更新日期：2017-11-20 00:00:00
abstract：:NADPH in microsomes reduces the hydroxocob(III)alamin form of vitamin B12 to cob(II)alamin and the supernucleophilic cob(I)alamin, which are both highly reactive toward xenobiotic epoxides formed by mammalian metabolism of dienes such as the industrially important chemicals chloroprene and 1,3-butadiene. With styrene,...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0497898
更新日期：2004-12-01 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
pub_type： 杂志文章
doi：10.1021/tx300457f
更新日期：2013-03-18 00:00:00
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
doi：10.1021/tx020013l
更新日期：2002-10-01 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
pub_type： 杂志文章
doi：10.1021/tx400205n
更新日期：2013-08-19 00:00:00
abstract：:Epidemiological evidence suggests a lower incidence of Parkinson's disease in smokers than in nonsmokers. This evidence, together with the lower levels of brain monoamine oxidase (MAO) activity in smokers and the potential neuroprotective properties of MAO inhibitors, prompted studies which led to the isolation and ch...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx000224v
更新日期：2001-05-01 00:00:00
abstract：:The tumorigenic activity of manufactured gas plant residue (MGP) was evaluated in female A/J mice using a F0927 basal gel diet system. Adulterated diets containing MGP (0.10% or 0.25%) or benzo[a]pyrene (B[alpha]P; 16 or 98 ppm) were fed for 260 days. A negative control group was maintained on a nonadulterated basal g...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00049a008
更新日期：1995-10-01 00:00:00
abstract：:Today much is known about cytochrome P450 (P450) enzymes and their catalytic specificity, but the range of reactions catalyzed by each still continues to surprise. Historically, P450s had been considered to be involved in either the metabolism of xenobiotics or endogenous chemicals, in the former case playing a genera...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.6b00226
更新日期：2017-01-17 00:00:00
abstract：:All pesticides must go through a rigorous risk assessment process in order to show that they are safe for use.With respect to dermal risk assessment for re-entry workers, the absorption value applied to predict systemic dose from this external exposure is obtained by testing liquid forms of the pesticide in vivo and/o...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx500509z
更新日期：2015-02-16 00:00:00
abstract：:Deoxynivalenol (DON) is a trichothecene mycotoxin that is produced by several species of Fusarium, which may infect grain crops. DON, as well as other type-B trichothecenes, contain an α,β-unsaturated carbonyl group that may react with sulfhydryl groups in, for example, amino acids and peptides. Such conjugates have b...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00385
更新日期：2020-02-17 00:00:00
abstract：:It is well-known that aromatic diamino-, dihydroxy-, and amino-hydroxy compounds, with NH(2) and OH groups in ortho- or para-positions relative to each other, are strong skin sensitizers. In this paper, we analyze published potency and cross-reactivity data, whereby animals sensitized to one of these compounds are cha...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9000336
更新日期：2009-09-01 00:00:00
abstract：:The conformation of the crotonaldehyde-derived N(2)-[3-oxo-1(S)-methyl-propyl]-dG adduct in the oligodeoxynucleotide 5'-d(G(1)C(2)T(3)A(4)G(5)C(6)X(7)A(8)G(9)T(10)C(11)C(12))-3'.5'-d(G(13)G(14)A(15)C(16)T(17)C(18)G(19)C(20)T(21)A(22)G(23)C(2)(4))-3', where X = N(2)-[3-oxo-1(S)-methyl-propyl]-dG, is reported. This addu...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0600604
更新日期：2006-08-01 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：:The reduced transcriptomic approach allows full dose range testing of hundreds of chemicals or mixtures using human cells or zebrafish embryos. Points of departure of genes and pathways can be used for potency ranking and to classify chemicals by disrupted biological pathways. ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00104
更新日期：2018-07-16 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：:While considerable effort has been expended on determining the health effects of exposure to typical urban concentrations of O3, little is known about the chemical events responsible for toxicity. Phospholipids containing unsaturated fatty acids in the cell membranes of lung cells are likely reaction sites for inhaled...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00025a023
更新日期：1992-01-01 00:00:00
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
doi：10.1021/acs.chemrestox.5b00071
更新日期：2015-06-15 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
pub_type： 杂志文章
doi：10.1021/tx400098z
更新日期：2013-05-20 00:00:00
abstract：:Increasing exposure of biological systems to large amounts of polycyclic aromatic hydrocarbons is of great public concern. Organisms have an array of biological defense mechanisms, and it is believed that mucosal gel (which covers the respiratory system, the gastrointestinal tract, etc.) provides an effective chemical...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx100426s
更新日期：2011-03-21 00:00:00
abstract：:Hydroxyl radical can be induced from Fenton reaction or gamma radiolysis of water. It can add preferentially to the C5 position of thymidine to give the 5-hydroxy-5,6-dihydrothymidin-6-yl radical. In this report, we examined the independent generation and reactivity of this radical in oligodeoxyribonucleotides (ODNs)....
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx050195u
更新日期：2005-12-01 00:00:00
abstract：:Chloroethylnitrosoureas (CENUs) are bifunctional alkylating agents widely used for the clinical treatment of cancer. They exert anticancer activity by inducing DNA interstrand cross-links (ICLs) within GC base pairs to form dG-dC cross-links. This lesion inhibits DNA double strand separation during replication and tra...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx500143b
更新日期：2014-07-21 00:00:00
abstract：:Quantitative structure-activity relationships (QSAR's) are described for the rate of conjugation of a series of fluoronitrobenzenes with cytosolic as well as with two major alpha and mu class enzymes of rat and human liver, viz., glutathione S-transferases (GST) 1-1, 3-3, A1-1, and M1a-1a. For all purified enzymes stu...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9501804
更新日期：1996-04-01 00:00:00
abstract：:The seaweed Fucus vesiculosus is unusual when compared with other algal species, in that it can survive in toxic-metal-contaminated aquatic environments. The metallothionein gene has been identified in F. vesiculosus by Kille and co-workers (Morris, C. A., Nicolaus, B., Sampson, V., Harwood, J. L., and Kille, P. (1999...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx050206j
更新日期：2006-03-01 00:00:00
abstract：:Guidance from the Food and Drug Administration on drug interaction studies does not include a specific section on contributions of metabolites to observed inhibitory drug-drug interactions, and the quantitative role of drug metabolites in inhibitory drug-drug interactions is not presently known. The current work was u...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/tx800491e
更新日期：2009-02-01 00:00:00
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
更新日期：2012-03-19 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：:Metabolically formed dihydrodiol epoxides in the bay-region of polycyclic aromatic hydrocarbons are thought to be responsible for the genotoxic properties of these environmental pollutants. The hexacyclic aromatic hydrocarbon dibenzo[def,mno]chrysene (anthanthrene), although lacking this structural feature, was found ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx010131t
更新日期：2002-03-01 00:00:00
abstract：:Hydrazyl radical intermediates have been suggested as important intermediates in the biochemistry of hydrazides and hydrazines. Although spin-trapping studies have intercepted those species previously, there has been no report of the direct observation of the unstable hydrazyl radicals of isoniazid and iproniazid. We ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0341759
更新日期：2004-02-01 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
pub_type： 杂志文章
doi：10.1021/tx300505v
更新日期：2013-03-18 00:00:00
