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13. Anomalous behaviour in the phase transition and crystal structure of urea adducts with n-eicosane
- ej.iop.org
- Anomalous behaviour in the phase transition and crystal structure of urea adducts with n-eicosane .
- X-ray diffraction measurements are made for urea adducts with n-eicosane to investigate the arrangement of n-eicosane molecules in the channels formed by urea molecules. ... This kind of Bragg reflection has not been observed for other n-alkanes in urea adducts. ...
14. IWA Publishing - Water books, journals, & reports - Catalogue - Identification and Quantitation of DNA Adducts Derived From DBPs
- www.iwapublishing.com
- Identification and Quantitation of DNA Adducts Derived From DBPs .
- The research demonstrated that several carcinogenic DBPs do not form direct DNA adducts and do not enhance endogenous adducts. ...
15. Proteomic Analysis of Arginine Adducts on Glyoxal-modified Ribonuclease -- Cotham et al. 3 (12): 1145 -- Molecular & Cellular Proteomics
- www.mcponline.org
- Proteomic Analysis of Arginine Adducts on Glyoxal-modified Ribonuclease* .
- Arg39 and Arg85, which are closest to the active site of the enzyme, were identified as the primary sites of formation of the glyoxal-derived dihydroxyimidazolidine and hydroimidazolone adducts. ... We conclude that dihydroxyimidazolidine adducts are the primary products of modification of protein by glyoxal, that Arg39 and Arg85 are the primary sites of modification of RNase by glyoxal, and that modification of arginine residues during Maillard reactions of proteins is a highly selective process. ...
- Glucose and its oxidative degradation products, including glyoxal (13), are able to modify reactive side chains of amino acids in proteins under physiological conditions to form a diverse group of protein-bound adducts known as advanced glycation end-products (AGEs). ...
- Glyoxal and glycolaldehyde are products of autoxidation of glucose or glucose adducts to proteins. Other carbohydrates, such as fructose, arabinose, and ascorbate, may also degrade to glyoxal, possibly through intermediate adducts to protein. ...
- Formation of glyoxal-derived dihydroxyimidazolidines (G-DH1 and G-DH2), glyoxal-derived hydroimidazolones (G-H1, G-H2 and G-H3) and N-(carboxymethyl)arginine (CMA) adducts by reaction of glyoxal with arginine residues on protein.
- In previous work (11) on chemical modification of the model protein RNase by glucose, we concluded that CML was formed primarily by oxidation of Amadori adducts of glucose to protein and that free glyoxal, which was also formed in the reaction system, was not a significant precursor of CML. ...
- To investigate whether the modified peptide in the glyoxal incubations was G-DH or CMA or both adducts on Arg39 or CML on Lys41, protein from the 7-day 1 mM glyoxal reaction was incubated with a 5-fold molar excess (based on carbonyl groups) of HA. ...
- Thus, the discharge of G-DH adducts was dependent on reaction with HA. ...
- Site Specificity and Kinetics of Formation of G-DH and G-H Adducts.
- Peptides 8FK31 and 67NK98, containing, respectively, Arg10 and Arg85 modified to G-DH and G-H, were located by extracting ion chromatograms from the full-scan data, thus establishing the formation of both of these adducts at Arg10 and Arg85. ... Peptide 32SK37 with Arg33 modified to either G-DH or G-H was not detected in the RNase-glyoxal reactions, despite a strong signal for the native peptide 34NLTK37, indicating that Arg33 was not converted to these adducts in detectable amounts in the glyoxal incubations, even after 7 days in 5 mM glyoxal. ...
- The 3+ ions of the G-DH adducts of peptides 8FK31 and 67NK98, and the G-H adduct of peptide 38DK61 were also detected in the single combined spectrum that was extracted from the full-scan data of the glyoxal incubations, but not from the glucose incubations (Fig. 2, D, F, I, and K), and their retention times match those expected for these adducts. ...
- Arg39 and Arg85 are the main sites of formation of G-DH/CMA and G-H adducts when RNase is incubated with 1 mM glyoxal. Kinetics of (A) loss of unmodified peptides, (B) formation of G-DH/CMA adducts, (C) formation of G-H adducts. ...
16. Project: Redoxcycling and toxicity of catechol containing flavonoids and their glutathione adducts ()
- www.niwi.nl
- Project: Redoxcycling and toxicity of catechol containing flavonoids and their glutathione adducts.
- Redoxcycling and toxicity of catechol containing flavonoids and their glutathione adducts.
- The formation of these glutathionyl-flavonoid adducts provides evidence for the actual pro-oxidative formation of reactive quinone type metabolites from B ring catechol flavonoids in the selected cellular in vitro model using melanoma cells. ...
17. Altered Formation of Topotecan-Stabilized Topoisomerase I-DNA Adducts in Human Leukemia Cells -- Kaufmann et al. 89 (6): 2098 -- Blood
- www.bloodjournal.org
- Altered Formation of Topotecan-Stabilized Topoisomerase I-DNA Adducts in Human Leukemia Cells .
- In the present study, a band depletion assay was used to evaluate the ability of TPT to stabilize topo I-DNA adducts in human leukemia cell lines and in clinical leukemia samples ex vivo. ... These observations raise the possibility that formation of topo I-DNA adducts is diminished in many specimens of refractory/relapsed acute leukemia by a mechanism that might alter topo I sensitivity to TPT. ...
- Interaction of these topo I-DNA adducts with replication complexes results in the formation of small numbers of cytotoxic DNA double-strand breaks, which in turn set in motion events resulting in tumor cell apoptosis. ...
- 11-13 Second, cells with diminished topo I content form fewer topo I-DNA adducts and are resistant to this class of agents (reviewed in Slichenmyer et al,1 Chen and Liu,2 Potmesil,3 and Pommier et al4; see also Sorensen et al14 ). Finally, cells with alterations in topo I that affect the drug-induced stabilization of topo I-DNA adducts are resistant to this class of agents. ... However, Goldwasser et al15 have recently reported that the concentration of CPT required to stabilize topo I-DNA adducts varies dramatically among previously untreated colon cancer cell lines, even though the cell lines have similar CPT accumulation and similar topo I content. These observations raise the possibility that some other difference in topo I, possibly a posttranslational modification, might also affect the ability of this class of agents to stabilize topo I-DNA adducts. ...
- As an adjunct to two phase I trials of TPT in acute leukemia, we studied the formation of TPT-stabilized topo I-DNA adducts in marrow mononuclear cells from patients receiving TPT-containing reinduction chemotherapy. ... Accordingly, as increasing topo I-DNA adducts are formed in the presence of TPT, a corresponding decrease in the molecular weight (Mr ) ~100,000 signal for topo I is observed on immunoblots. ... Interestingly, sequential assays performed in cells from a single patient harvested before administration of TPT and 8 weeks later at the time of leukemic regrowth indicated that the TPT concentration required to stabilize topo I-DNA adducts was higher at relapse, even though the cellular topo I content and TPT accumulation did not decrease. ...
- A band depletion assay was used to study the TPT-induced stabilization of topo I-DNA adducts in intact leukemia cells. ...
- The band depletion assay was used to prospectively examine the formation of topo I-DNA adducts in leukemic marrow samples. ...
- Interestingly, comparison of these samples showed a marked increase in the TPT concentration required to stabilize topo I-DNA adducts at the time the leukemia regrew (Fig 4C). ...
- The requirement for elevated TPT concentrations to stabilize the topo I-DNA adducts might reflect diminished TPT accumulation or altered ability of TPT to stabilize topo I-DNA adducts. ... These results suggest that differences in TPT accumulation do not account for the 30-fold range of TPT concentrations required to stabilize topo I-DNA adducts in intact cells. ...
18. DNA adducts, detected by 32P postlabelling, in human cholangiocarcinoma -- Khan et al. 52 (4): 586 -- Gut
- gut.bmjjournals.com
- DNA adducts, detected by 32P postlabelling, in human cholangiocarcinoma .
- Aims: To investigate and compare tumour and tumour adjacent CCa tissue, and non-cancer control bile duct tissue, for DNA adducts as a biomarker of genotoxin exposure. ...
- Methods: DNA from 32 intrahepatic CCa patients (and in 28 cases DNA from adjacent non-tumour tissue) and from biliary ducts of seven non-cancer patients were investigated for the presence of DNA adducts using the nuclease P1 method of 32P postlabelling. DNA adduct levels (number of adducts/108 nucleotides) were quantified. ...
- Conclusion: Quantitative and qualitative differences in adducts between cancer and non-cancer patients support the hypothesis that genotoxins may play a role in the development of intrahepatic CCa. ...
- Keywords: cholangiocarcinoma; DNA adducts; 32P postlabelling.
- DNA adducts.
- DNA adducts are covalently modified bases resulting from binding of electrophilic carcinogens, or their metabolites, at the nucleotide level. ... 10 It is a key step in chemically induced carcinogenesis as mis- or unrepaired adducts can lead to mutation. 1012 As well as causing mutations, DNA adducts contribute to induction of carcinogenesis by chromosomal damage. The formation of DNA adducts in various human tissues has been extensively studied as a biomarker of exposure to occupational and other carcinogens in high risk populations. 1218 Most studies considering the association between cancer at different sites and adduct levels have shown that cancer cases have higher levels of adducts than non-cancer controls. ... Several studies have shown that DNA adducts are induced in human as well as rodent livers following exposure to carcinogenic chemicals. ... 25 DNA adducts have also been detected in human liver cells following exposure to steroid hormones26 and polychlorinated biphenyls. 27 Induction of DNA adducts has also been linked to the initiation of neoplasia leading to malignant change in haemachromatosis patients. ...
- In over 200 studies, DNA adducts have been detected in various human tissues, including the liver, lung, colon, bladder, breast, cervix, brain, blood lymphocytes, and stomach. ...
19. Ions and Radicals
- www.chem.qmw.ac.uk
- -adducts:.
- Adducts, involving a dipolar bond with electron donation from and/or to -orbitals. ...
- -complexes: See -adducts.
- Meisenheimer complexes/compounds/adducts:.
- pi-adducts: See -adducts under 'a'.
- pi-complexes: See -adducts under 'a'. ...
20. Cisplatin-DNA adducts inhibit translocation of the Ku subunits of DNA-PK -- Turchi et al. 28 (23): 4634 -- Nucleic Acids Research
- nar.oupjournals.org
- CisplatinDNA adducts inhibit translocation of the Ku subunits of DNA-PK .
- The Ku DNA binding subunits of DNA-PK display a reduced ability to translocate on duplex DNA containing cisplatinDNA adducts compared to control, undamaged duplex DNA. ... In addition to a decrease in DNA-PKcs association, the DNA-PKcs that is bound with Ku at a DNA end containing cisplatinDNA adducts has a reduced catalytic rate compared to heterotrimeric DNA-PK assembled on undamaged DNA. ... The presence of cisplatin adducts decreases the ability to translocate away from the terminus and results in the formation of inactive kinase complexes at the DNA terminus. ...
- Cisplatin is a DNA-damaging agent that forms coordinate covalent DNA adducts. The formation of cisplatinDNA adducts results in cell cycle arrest, inhibition of DNA replication and transcription, and eventually apoptosis. ...
- We have demonstrated previously that on short duplex DNA molecules 25 bp in length, the affinity of the Ku subunits of DNA-PK is not dramatically altered when the DNA contains various cisplatin DNA adducts (14). ... Upon the introduction of cisplatinDNA adducts (lanes 512), a clear change in the product distribution was observed. ... These data demonstrate that the presence of cisplatinDNA adducts results in a decrease in the number of Ku molecules that are bound to a single DNA substrate. ...
- The effect of cisplatinDNA adducts on the binding of Ku to a duplex 119 bp DNA. ...
- For these experiments a 59 bp duplex DNA was employed and was modified to contain six cisplatin 1,2-d(GpG) adducts at defined locations. ...
- Binding assays were performed with 50 fmol of undamaged DNA (lanes 15) or the same DNA containing six cisplatin d(GpG) adducts (lanes 610). ...
- Kinase activation using a 59 bp DNA substrate with multiple cisplatin adducts. ...
- To address this question, a series of DNA substrates were prepared with site-specific cisplatinDNA adducts at defined distances from the DNA termini. To facilitate the direct comparison of these DNA substrates, the adducts were placed an equal distance from each end on a given DNA molecule and the total length of the DNA was varied to allow for the different distances between the DNA termini and the adduct. Duplex substrates of size 30, 41 and 120 bp were prepared with centrally located cisplatin adducts such that the distances of the lesion from the termini was 14, 20 and 60 bases, respectively. ...
21. Nat'l Academies Press, Drinking Water and Health, Volume 9 (1989), 1 Biologic Significance of DNA Adducts and Protein Adducts
- books.nap.edu
- 1 Biologic Significance of DNA Abducts and Protein AdJucts Current evidence suggests associations between the occurrence of adducts formed by specific compounds and various types of toxicity, such as mu- tation, cancer, and developmental effects. ... DNA adducts form in many tissues, but some of them might be early markers of disease that could be reversed (NRC, 19871. This chapter 'describes what is known about mech- anisms and rates of DNA-adduct formation and removal, the significance of the adduct's position on the DNA, And the correlation of of adducts of certain specific compounds with toxic effects. In addition, protein adducts are dis- cussed as possible markers of exposure. Studies of laboratory animals and human chemotherapy patients have sug- gested that DNA adducts can serve as biologic dosimeters in providing es- timates of exposure, dose to the target tissue, and sometimes mutagenicity and carcinogenicity (Anderson, 1987; Wogan, 19881. ... And the use of DNA adducts could perhaps reduce the uncertainty in quantitative risk assessment by providing better dose in- formation for dose-response evaluation. The use of DNA adducts to measure biologically effective dose is scientifically appealing. DNA adducts can in- dicate a measurable dose at a target site and thus make it possible to bypass 6 .
- Biologic Significance of DNA Adducts and Protein Adducts 7 ~ 10-5 ~. ...
- Measuring DNA adducts provides one way to understand and even measure those differences. The following are examples: · Male mice produce different types of DNA adducts from, and more hepatocarcinomas than, female mice after exposure to the same doses of the hepatocarcinogen N-hydroxy-2-acetylaminofluorene (B Bland et al. ... · Rat hepatocytes have a much greater metabolic ability than hepatic sinusoidal cells to activate diethylnitrosamine and thus form DNA adducts (Lewis and Swenberg, 19831. ...
- Biologic Significance of DNA Adducts and Protein Adducts 9 of DNA abducts. ... Thus, higher concentrations of the compound do not necessarily result in greater numbers of adducts (Belinsky et al. ... , 1984) in forming DNA adducts and in binding covalently to DNA is greater per unit dose at high exposures, but in a nonlinear fashion. ... New unsensitive methods of detection make it possible to monitor DNA adducts in animals at exposures below those feasible in chronic bioassays and closer to those expected in the human population. ... Some problems in using DNA adducts to estimate human risks are related to differences between rodents and humans. We can calculate the risk as- sociated with DNA adducts in experimental animals, but interspecies ex- trapolations remain difficult to validate. Many experiments cannot ethically be performed in humans, and DNA adducts in human target cells or tissues would be expected to vary widely because of individual variations in DNA metabolism and repair. ... The overall estimation of DNA adducts might not be useful, unless one can determine the ratio of biologically important to unimportant adducts. ...
22. Hydroxynonenal inactivates cathepsin B by forming Michael adducts with active site residues -- Crabb et al. 11 (4): 831 -- Protein Science
- www.proteinscience.org
- Hydroxynonenal inactivates cathepsin B by forming Michael adducts with active site residues .
- Purified bovine cathepsin B treated briefly with 15 µM HNE lost 76% of its protease activity and also developed immunoreactivity with antibodies to HNE adducts in Western blot analysis. After stabilization of the potential Michael adducts by sodium borohydride reduction, modified amino acids were localized within the bovine cathepsin B protein structure by mass spectrometric analysis of tryptic peptides. Michael adducts were identified by tandem mass spectrometry at cathepsin B active site residues Cys 29 (mature A chain) and His 150 (mature B chain). ...
- Keywords: Oxidative damage; hydroxynonenal; cathepsin B; Michael adducts; mass spectrometry.
- 1) and forms Schiff base linkages with primary amino groups and Michael adducts with Lys, His, and Cys residues and also forms fluorescent cross-links (Esterbauer et al. ...
- HNE Michael adducts. HNE (4-hydroxy-2-nonenal) is generated by oxidative cleavage of linoleic (LA) and arachidonic acid (AA) containing phospholipids and can condense with lysine, cysteine, and histidine residues to form Michael adducts. Reduction with NaBH4 stabilizes Michael adducts. ...
- HNE inactivates purified bovine cathepsin B and generates covalent adducts.
- HNE treatment of cathepsin B was terminated after 15 min by addition of 8 M urea, and the preparation was subjected to sodium dodecyl (SDS)PAGE and Western analysis using an antibody that recognizes HNE Michael adducts (Uchida et al. ...
- Activated bovine cathepsin B was incubated for 1 h with 15 µM HNE and then subjected to SDS-PAGE (1 µg/lane) and Western analysis using a rabbit polyclonal antibody to HNE adducts (Uchida et al. ...
- Identification of Michael adducts in HNE treated cathepsin B.
- 1 is characteristic of reduced HNE Michael adducts (Fig. ... Both AT4 and BT10 also were detected without Michael adducts, indicating that the 8-min HNE treatment did not yield quantitative modification of the intact protein. No other peptides with Michael adducts were observed by LC ESMS. ...
23. Albumin Adducts of Benzene Oxide and 1,4-Benzoquinone as Measures of Human Benzene Metabolism -- Rappaport et al. 62 (5): 1330 -- Cancer Research
- cancerres.aacrjournals.org
- Albumin Adducts of Benzene Oxide and 1,4-Benzoquinone as Measures of Human Benzene Metabolism1 .
- Albumin adducts of benzene oxide (BO-Alb) and 1,4-benzoquinone (1,4-BQ-Alb) were investigated among 134 workers exposed to benzene and 51 unexposed controls in Tianjin, China. Concentrations of both adducts increased with benzene exposure range = 0. ... This study illustrates that Alb adducts can be used to investigate the dispositions of reactive metabolites of procarcinogens in humans, provided that exposures are adequately characterized in the month preceding blood collection. ...
- Because reactive metabolites are short lived, these studies have relied on Hb and Alb adducts to gain insight into the dispositions of the electrophilic intermediates, a strategy first suggested by Ehrenberg et al. ... Stable Alb and Hb adducts have mean residence times in exposed persons of 1 and 4 months, respectively (19). Unlike short-lived urinary metabolites, Alb and Hb adducts damp the variability in exposure from day to day thereby illuminating connections between biomarkers and exposure (20 , 21). ...
- Studies of protein adducts in benzene-exposed humans have focused primarily on cysteinyl binding of BO and 1,4-BQ with serum Alb (hereafter designated BO-Alb and 1,4-BQ-Alb, respectively) among heavily exposed workers. ... 7328 ppm), and detected background adducts (of unknown origin) among 44 unexposed subjects. ... In the current investigation we report levels of Alb adducts of BO and 1,4-BQ among 134 benzene-exposed workers (range: 0. ...
- To examine the inter- and intraindividual variation of Alb adducts, repeated blood samples were obtained from 11 exposed subjects (6 men and 5 women) from the glue factory on three consecutive Mondays (1 subject provided two samples). ...
- One sample was lost during processing, so plasma samples from a total of 184 exposed and control subjects were assayed for Alb adducts. ...
- Adducts were measured without knowledge of individual subjects or exposure status. ...
- Analysis of Alb Adducts.
- Median levels of exposures and adducts, aggregated by exposure status and/or gender, were compared with the Wilcoxon two sample test. ...
- The subject-specific GM levels of the two adducts (pmol/g Alb) and their difference, representing ln (1,4-BQ-Alb)/(BO-Alb) , were regressed on the corresponding subject-specific exposures to benzene and toluene. ...
24. Carcinogen macromolecular adducts and their measurement -- Poirier et al. 21 (3): 353 -- Carcinogenesis
- carcin.oupjournals.org
- Carcinogen macromolecular adducts and their measurement .
- DNA adducts.
- Protein adducts.
- Damage to DNA induced by carcinogenic chemicals reflects exposure and is directly related to tumor formation, whereas modification of protein provides relatively precise dosimetry for stable adducts of proteins with a known half-life. Sophisticated methods for the detection and quantitation of DNA and protein adducts have been developed during the last ~25 years. For DNA adducts the most widely used methods include electrochemical detection, mass spectrometry, fluorescence and phosphorescence spectroscopy, immunoassays and immunohistochemistry and 32P-post-labeling. ... Methods for the determination of protein adducts include immunoassay and a variety of elegant high-resolution mass spectrometry approaches. ... 1 fmol for protein adducts, is based primarily on method specificity and the availability of large quantities of sample material. ...
- DNA adducts.
- Protein adducts.
- The last two decades have witnessed the development of sophisticated assays for the measurement of DNA and protein adducts. Previously, macromolecular adduct measurements typically required administration of a radiolabeled carcinogen, and measurement of adducts in chronic exposure studies or in human tissues was extremely rare. ...
- Currently, a large body of literature validates the use of molecular dosimetry for both DNA adducts and protein adducts for many carcinogen exposures (17). ... This review will focus on some of the major advances in research on carcinogen macromolecular adducts that have been achieved in the last two decades. ...
- DNA adducts .
- DNA adducts.
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