当前位置： SCI文献检索 > CHEMICAL RESEARCH IN TOXICOLOGY期刊下所有文献 > Intracellular activation of cytotoxic agents: kinetic models for methylnitrosoureas and N-methyl-N'-nitro-N-nitrosoguanidine in cell culture.

Intracellular activation of cytotoxic agents: kinetic models for methylnitrosoureas and N-methyl-N'-nitro-N-nitrosoguanidine in cell culture.

Abstract：

:The cytotoxic activity of N-methyl-N-nitrosourea (MNU), streptozotocin, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was determined in cell culture by using a P388 cell growth rate inhibition assay. These agents appear to have very different activities when inhibition is related to the agent concentration in the culture medium: ED50(C0) = 40 microM for MNNG to 875 microM for streptozotocin. The mechanism of action of these three agents involves conversion to the active methanediazonium ion and subsequent methylation of cellular macromolecules. As a consequence, the rates of conversion of the parent agent to the methylating species in the medium and within the cell are important parameters that also need to be considered to reach a more detailed understanding of the mechanism of action. In order to do this, a kinetic model has been developed to calculate the concentration of drug that is converted to active methylating species within the cell during the assay incubation period. The use of cell culture kinetic models was extended from simple compounds activated through solvolytic reactions (nitrosoureas) to an agent that undergoes selective intracellular activation (MNNG). By use of measured values for initial drug concentration, incubation time, and cell volume, as well as extracellular and intracellular chemical activation rate constants, the intracellular concentration, [P4], which represents the cumulative intracellular reaction products formed during the incubation period, was calculated and related to cytotoxicity. All three agents showed an ED50[P4] between 140 and 180 microM, and for MNNG, this ED50 was independent of extracellular sulfhydryl concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Chem Res Toxicol

journal_title

Chemical research in toxicology

authors

Weinkam RJ,Dolan ME

doi

10.1021/tx00009a006

subject

Has Abstract

pub_date

1989-05-01 00:00:00

pages

157-61

issue

3

eissn

0893-228X

issn

1520-5010

journal_volume

2

pub_type

杂志文章

相关文献

CHEMICAL RESEARCH IN TOXICOLOGY文献大全
  • 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

    doi：10.1021/tx010065v

    authors： von Weymarn LB,Murphy SE

    更新日期：2001-10-01 00:00:00

  • Bisphenol A activates the Nrf1/2-antioxidant response element pathway in HEK 293 cells.

    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

    pub_type： 杂志文章

    doi：10.1021/tx400036v

    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

  • 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

  • Sulfur-containing arsenical mistaken for dimethylarsinous acid [DMA(III)] and identified as a natural metabolite in urine: major implications for studies on arsenic metabolism and toxicity.

    abstract：:It is vital that methylated trivalent arsenicals [MA(III) and DMA(III)] are described and characterized unequivocally due to their high toxicity. Two different ways of generating the methylated trivalent arsenicals have been practiced-reduction of the methylated pentavalent arsenical either by the sodium-metabisulfite...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx049978q

    authors： Hansen HR,Raab A,Jaspars M,Milne BF,Feldmann J

    更新日期：2004-08-01 00:00:00

  • Internalization of carbon black and maghemite iron oxide nanoparticle mixtures leads to oxidant production.

    abstract：:The risk of potential human exposure to mixed nanomaterials in consumer, occupational, and medicinal settings is increasing as nanomaterials enter both the workplace and the marketplace. In this study, we investigated the toxicity of mixed engineered carbon black (ECB) and maghemite iron oxide (Fe(2)O(3)) nanoparticle...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx100307h

    authors： Berg JM,Ho S,Hwang W,Zebda R,Cummins K,Soriaga MP,Taylor R,Guo B,Sayes CM

    更新日期：2010-12-20 00:00:00

  • Toxicant Deposition and Transport in Alveolus: A Classical Density Functional Prediction.

    abstract：:The deposition and transport of toxicants on pulmonary surfactant are important processes in human health and medical care. We have introduced classical density functional theory (CDFT) to provide insight into this process. Nine typical toxicants in PM2.5 were considered, and their free energy and structural informati...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.8b00272

    authors： Liu H,Liu Y,Shang Y,Liu H

    更新日期：2018-12-17 00:00:00

  • Unveiling the Variability of "Quartz Hazard" in Light of Recent Toxicological Findings.

    abstract：:The variability of quartz hazard stands as one of the most puzzling issues in particle toxicology, notwithstanding the fact that silicosis, the most ancient occupational disease, was the very topic from which the study of the toxicity of particulates developed. Over the years, other adverse effects of silica particles...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.6b00409

    authors： Pavan C,Fubini B

    更新日期：2017-01-17 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

    doi：10.1021/tx0002278

    authors： Liang Q,Dedon PC

    更新日期：2001-04-01 00:00:00

  • Bioactivation of the selective estrogen receptor modulator desmethylated arzoxifene to quinoids: 4'-fluoro substitution prevents quinoid formation.

    abstract：:Although selective estrogen receptor modulators (SERMs) are useful in the treatment and prevention of breast cancer, the SERM tamoxifen has been associated with an increased risk of endometrial cancer possibly due to metabolism to electrophilic quinoids. Another SERM, arzoxifene is currently in clinical trials for the...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx049776u

    authors： Liu H,Liu J,van Breemen RB,Thatcher GR,Bolton JL

    更新日期：2005-02-01 00:00:00

  • Oxidation of polychlorinated biphenyls by liver tissue slices from phenobarbital-pretreated mice is congener-specific and atropselective.

    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

    pub_type： 杂志文章

    doi：10.1021/tx400229e

    authors： Wu X,Duffel M,Lehmler HJ

    更新日期：2013-11-18 00:00:00

  • Mapping serum albumin adducts of the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by data-dependent tandem mass spectrometry.

    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

    pub_type： 杂志文章

    doi：10.1021/tx300253j

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

    更新日期：2012-10-15 00:00:00

  • Enzyme-linked immunosorbent assay for the specific detection of the mercapturic acid metabolites of naphthalene.

    abstract：:The measurement of metabolites constitutes a useful tool for detection of exposure and in pharmacokinetic studies. Epoxidation with subsequent glutathione conjugation and mercapturic acid formation is an important deactivation pathway for naphthalene, a toxin which presumably causes lung disease. The mercapturic acid ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00033a006

    authors： Marco MP,Nasiri M,Kurth MJ,Hammock BD

    更新日期：1993-05-01 00:00:00

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

    abstract：: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 ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx4003963

    authors： Wang C,Zhang Q,Qian Y,Zhao M

    更新日期：2014-04-21 00:00:00

  • DNA adducts from nitroreduction of 2,7-dinitrofluorene, a mammary gland carcinogen, catalyzed by rat liver or mammary gland cytosol.

    abstract：:Nitrofluorenes are mutagenic and carcinogenic environmental pollutants arising chiefly from combustion of fossil fuels. Nitro aromatic compounds undergo nitroreduction to N-hydroxy arylamines that bind to DNA directly or after O-esterification. This study analyzes the DNA binding and adducts from the in vitro nitrored...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx010172p

    authors： Ritter CL,Culp SJ,Freeman JP,Marques MM,Beland FA,Malejka-Giganti D

    更新日期：2002-04-01 00:00:00

  • Studies on 4-benzyl-1-methyl-1,2,3,6-tetrahydropyridine, a nonneurotoxic analogue of the parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

    abstract：:Previous reports indicate that 4-benzyl-1-methyl-1,2,3,6-tetrahydropyridine (BMTP), the benzyl analogue of the Parkinsonian inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is not neurotoxic in the C-57 black mouse even when administered at a dose 10 times greater than the dose of MPTP required...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00014a008

    authors： Naiman N,Rollema H,Johnson E,Castagnoli N Jr

    更新日期：1990-03-01 00:00:00

  • Potent mutagenicity of 3-methylindole requires pulmonary cytochrome P450-mediated bioactivation: a comparison to the prototype cigarette smoke mutagens B(a)P and NNK.

    abstract：:3-Methylindole (3MI) is a preferential pneumotoxicant found in cigarette smoke. A number of lung-expressed human cytochrome P450 enzymes, including 1A1, 2F1, and 2A13, catalyze the metabolism of 3MI to reactive intermediates that fragment DNA, measured with the Comet assay to assess DNA damage, in a cytochrome P450-de...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx100147z

    authors： Weems JM,Lamb JG,D'Agostino J,Ding X,Yost GS

    更新日期：2010-11-15 00:00:00

  • Assessment of Single-Photon Ionization Mass Spectrometry for Online Monitoring of in Vitro Aerosol Exposure Experiments.

    abstract：:Chemical and physical characterization of transported evolving aerosols in an in vitro system is complex. The challenges include appropriate sampling sensitivity, measurement capabilities, and performing online measurements of constituents in the flowing aerosol during exposure. We assessed the performance of single-p...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.9b00381

    authors： Frege C,Asgari M,Steiner S,Ferreira S,Majeed S,Lucci F,Frentzel S,Hoeng J,Kuczaj AK

    更新日期：2020-02-17 00:00:00

  • Inactivation of the cytotoxic activity of repin, a sesquiterpene lactone from Centaurea repens.

    abstract：:Prolonged ingestion of Yellow Starthistle (Centaurea solstitialis) and Russian Knapweed (Centaurea repens) by horses has been shown to result in a fatal neurodegenerative disorder called equine nigropallidal encephalomalacia (ENE). Bioassay-guided fractionation of extracts from Centaurea species using the PC12 cell li...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx049864e

    authors： Tukov FF,Anand S,Gadepalli RS,Gunatilaka AA,Matthews JC,Rimoldi JM

    更新日期：2004-09-01 00:00:00

  • Carbon Disulfide Induces Embryo Implantation Disorder by Disturbing the Polarization of Macrophages in Mice Uteri.

    abstract：:Carbon disulfide (CS2) induces embryo implantation disorders. Macrophages participate in the process of pregnancy. Therefore, we want to explore the effects of CS2 exposure on polarization and immune function of macrophages in pregnant mice uteri. The exposure times were gestation days 3 (GD3), 4 (GD4), and 5 (GD5), a...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.9b00119

    authors： Zhang T,Hu C,Wu Y,Wang S,Liu X,Zhang D,Huang F,Gao H,Wang Z

    更新日期：2019-10-21 00:00:00

  • Determination of glycated nucleobases in human urine by a new monoclonal antibody specific for N2-carboxyethyl-2'-deoxyguanosine.

    abstract：:Sugars and sugar degradation products react in vivo readily with proteins (glycation) resulting in the formation of a heterogeneous group of reaction products, which are called advanced glycation end products (AGEs). AGEs notably change the structure and function of proteins so that extended protein-AGE formation is l...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx049929d

    authors： Schneider M,Thoss G,Hübner-Parajsz C,Kientsch-Engel R,Stahl P,Pischetsrieder M

    更新日期：2004-10-01 00:00:00

  • Proteins modified by the lipid peroxidation aldehyde 9,12-dioxo-10(E)-dodecenoic acid in MCF7 breast cancer cells.

    abstract：:The hydroperoxide of linoleic acid (13-HPODE) degrades to 9,12-dioxo-10(E)-dodecenoic acid (DODE), which readily modifies proteins. This study identified the major proteins in MCF7 cells modified by DODE. To reduce false positives, three methods were used to identify DODE-modified proteins. First, cells were treated w...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx9002808

    authors： Slade PG,Williams MV,Brahmbhatt V,Dash A,Wishnok JS,Tannenbaum SR

    更新日期：2010-03-15 00:00:00

  • Detoxication pathways involving glutathione and epoxide hydrolase in the in vitro metabolism of chloroprene.

    abstract：:Chloroprene (2-chloro-1,3-butadiene, 1) is an important industrial chemical, which is carcinogenic in experimental animals and possibly in humans. It is metabolized to the monoepoxides, 2-chloro-2-ethenyloxirane (2a,b) and (1-chloroethenyl)oxirane (3a,b), together with electrophilic chlorinated aldehydes and ketones. ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx034107m

    authors： Munter T,Cottrell L,Golding BT,Watson WP

    更新日期：2003-10-01 00:00:00

  • Tobacco alkaloids and tobacco-specific nitrosamines in dust from homes of smokeless tobacco users, active smokers, and nontobacco users.

    abstract：:Smokeless tobacco products, such as moist snuff or chewing tobacco, contain many of the same carcinogens as tobacco smoke; however, the impact on children of indirect exposure to tobacco constituents via parental smokeless tobacco use is unknown. As part of the California Childhood Leukemia Study, dust samples were co...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.5b00040

    authors： Whitehead TP,Havel C,Metayer C,Benowitz NL,Jacob P 3rd

    更新日期：2015-05-18 00:00:00

  • Synthesis and characterization of enantiomeric anti-2-fluorobenzo[a]pyrene-7,8-dihydrodiol-9,10-epoxides and their 2'-deoxyguanosine and oligodeoxynucleotide adducts.

    abstract：:Benzo[a]pyrene diol epoxides (BPDEs) are the ultimate carcinogenic species of benzo[a]pyrene, a prototype polycyclic aromatic hydrocarbon (PAH). BPDE-modified DNA duplexes can adopt multiple conformations depending on the nature of the modified bases, the stereochemistry at the location of the covalent linkage, and th...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx050308+

    authors： Yang T,Huang Y,Cho BP

    更新日期：2006-02-01 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

    doi：10.1021/tx960007n

    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

  • Arsenic-induced carcinogenesis--oxidative stress as a possible mode of action and future research needs for more biologically based risk assessment.

    abstract：:Exposure to inorganic arsenic (iAs) induces cancer in human lungs, urinary bladder, skin, kidney, and liver, with the majority of deaths from lung and bladder cancer. To date, cancer risk assessments for iAs have not relied on mechanistic data, as we have lacked sufficient understanding of arsenic's pharmacokinetics a...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章,评审

    doi：10.1021/tx900343d

    authors： Kitchin KT,Conolly R

    更新日期：2010-02-15 00:00:00

  • Particulate depleted uranium is cytotoxic and clastogenic to human lung cells.

    abstract：:Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and non-combatants is potentially frequent and widespread. DU is considered a suspected human carcinogen, affecting the bronchial cells of the lung. However, few investigations have studied DU in human bronchial cell...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx700026r

    authors： Wise SS,Thompson WD,Aboueissa AM,Mason MD,Wise JP Sr

    更新日期：2007-05-01 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

    doi：10.1021/tx2000976

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

    更新日期：2011-06-20 00:00:00

  • Low-density lipoprotein has an enormous capacity to bind (E)-4-hydroxynon-2-enal (HNE): detection and characterization of lysyl and histidyl adducts containing multiple molecules of HNE.

    abstract：:( E)-4-Hydroxynon-2-enal (HNE), an electrophilic bifunctional cytotoxic lipid peroxidation product, forms covalent adducts with nucleophilic side chains of amino acid residues. HNE-derived adducts have been implicated in many pathophysiological processes including atherosclerosis, diabetes, and Alzheimer's disease. Tr...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx8000303

    authors： Annangudi SP,Deng Y,Gu X,Zhang W,Crabb JW,Salomon RG

    更新日期：2008-07-01 00:00:00

  • Mechanism of cytochrome P450-catalyzed aromatic hydroxylation of estrogens.

    abstract：:The mechanism of aromatic hydroxylation of estrogens by cytochrome P450 enzymes has been examined by comparing the oxidation of estrone with that of substrates carrying additional aromaticity such as equilenin and the structural analog 2-naphthol. Hamster liver microsomes preferentially catalyzed the conversion of est...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx970021f

    authors： Sarabia SF,Zhu BT,Kurosawa T,Tohma M,Liehr JG

    更新日期：1997-07-01 00:00:00