Abstract:
:The growth-promoting effects of estrogens in hormone-dependent tumor tissues involve receptor-mediated pathways that are well-recognized; however, the role of estrogens in tumor initiation remains controversial. Estrogen metabolites, primarily the catechol estrogens (CE's), have been implicated in tumor initiation via a redox cycling mechanism. We have developed metabolically stable CE analogues for the study of receptor versus redox cycling effects on DNA damage. Comparisons between hydroxy estradiols (HE2's), methoxy estradiols (ME2's), and hydroxymethyl estradiols (HME2) in potentiometric and DNA damaging studies were made. DNA damage was assessed in calf thymus DNA using 8-oxo-2'-deoxyguanosine (8-oxo-dG) as a genotoxic marker for oxidative stress. Increases in the number of 8-oxo-dG/10(5) dG were significant for each 2-HE2 and 4-HE2. Cu(II)SO4, a transition metal known to catalyze the redox cycling of o-quinones, substantially increased the amount of DNA damage caused by both CE's. However, DNA damage was only observed at concentrations of 10 microM or higher, much greater than what is found under physiologic conditions. Furthermore, the presence of endogenous antioxidants such as glutathione, SOD, and catalase drastically reduced the amount of DNA damage induced by high concentrations of 2-HE2. There was no DNA damage observed for the non-redox cycling HME2's, making these compounds useful probes in the study of receptor-mediated carcinogenesis. Thus, both 2-HE2 and 4-HE2 are capable of producing oxidative DNA damage at micromolar concentrations in vitro. However, since the amount of CE's has not been shown to surpass nanomolar levels in vivo, it is unlikely that free radical production via redox cycling of CE's is a causative factor in human tumorigenesis.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Mobley JA,Bhat AS,Brueggemeier RWdoi
10.1021/tx980128isubject
Has Abstractpub_date
1999-03-01 00:00:00pages
270-7issue
3eissn
0893-228Xissn
1520-5010pii
tx980128ijournal_volume
12pub_type
杂志文章abstract::Chlorophyllin (CHL), a food-grade derivative of the green plant pigment chlorophyll, has recently been shown in this laboratory to be a potent inhibitor in vivo of hepatic aflatoxin B1 (AFB1)-DNA adduction and hepatocarcinogenesis (Breinholt et al. (1995) Cancer Res. 55, 57-62). We report here that CHL forms a strong ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00046a004
更新日期:1995-06-01 00:00:00
abstract::Methylmercury (MeHg) reacts readily with GSH, leading to the formation of a MeHg-SG adduct that is excreted into extracellular space through multidrug-resistance-associated protein (MRP), which is regulated by the transcription factor Nrf2. We previously reported that MeHg covalently modifies Keap1 and activates Nrf2 ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5002332
更新日期:2014-10-20 00:00:00
abstract::Thioureas are oxygenated by flavin-containing monooxygenases (FMOs), forming reactive sulfenic and/or sulfinic acids. Sulfenic acids can reversibly react with GSH and drive oxidative stress through a redox cycle. For this reason, thiourea S-oxygenation is an example of FMO-dependent bioactivation of a xenobiotic. Func...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx034253s
更新日期:2004-05-01 00:00:00
abstract::The oral dipeptidyl peptidase 1 (DPP1) inhibitor AZD5248 showed aortic binding in a rat quantitative whole-body autoradiography (QWBA) study, and its development was terminated prior to human dosing. A mechanistic hypothesis for this finding was established invoking reactivity with aldehydes involved in the cross-link...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00236
更新日期:2015-10-19 00:00:00
abstract::Oxidized nucleobases represent one of the main classes of damage induced in DNA by ionizing radiation. Emphasis was placed in this work on the measurement of four oxidized pyrimidine bases, including 5-(hydroxymethyl)uracil (5-HMUra), 5-formyluracil (5-ForUra), 5-hydroxycytosine (5-OHCyt), and 5-hydroxyuracil (5-OHUra...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960095b
更新日期:1996-10-01 00:00:00
abstract::There is interest in the relative toxicities of emissions from electronic cigarettes and tobacco cigarettes. Lists of cigarette smoke priority toxicants have been developed to focus regulatory initiatives. However, a comprehensive assessment of e-cigarette chemical emissions including all tobacco smoke Harmful and Pot...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00188
更新日期:2016-10-17 00:00:00
abstract::Exposure of individual histone proteins (H1, H2A, H2B, H3, or H4) and histone octamers (consisting of two molecules each of H2A, H2B, H3, and H4) to hydroxyl radicals, generated by gamma-irradiation, in the presence of O(2) generates protein-bound hydroperoxides in a dose-dependent fashion; this is in accord with prev...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx000053u
更新日期:2000-07-01 00:00:00
abstract::The guidelines embodied in this document were revised by the editors of the Publication Division of the American Chemical Society in January 1994 and endorsed by the Society Committee on Publications. ...
journal_title:Chemical research in toxicology
pub_type: 指南,杂志文章
doi:
更新日期:1994-07-01 00:00:00
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journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00127
更新日期:2016-07-18 00:00:00
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journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00051
更新日期:2020-05-18 00:00:00
abstract::Nuclear magnetic resonance (NMR) spectroscopy has traditionally been considered as an indispensable tool in elucidating structures of metabolites. With the advent of Fourier transform (FT) spectrometers, along with improvements in software and hardware (such as high-field magnets, cryoprobes, versatile pulse sequences...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800251p
更新日期:2009-02-01 00:00:00
abstract::Double-strand breaks are widely accepted to be the most toxic form of DNA damage. Molecules that produce double-strand breaks via a single chemical event are typically very cytotoxic and far less common than those that form single-strand breaks. It was recently reported that a commonly formed C4'-radical produces doub...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00032
更新日期:2015-04-20 00:00:00
abstract::Cytochrome P450 enzymes (CYPs) metabolize alkyl- and arylamines, generating several different products. For the primary and secondary amines, some of these reactions result in hydroxylated amines, which may be toxic. Thus, when designing new drugs containing amine groups, it is important to be able to predict if a giv...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500371a
更新日期:2015-04-20 00:00:00
abstract::Ferroptosis is a form of cell death that requires phospholipid peroxidation and has attracted increased attention, both as a means to eradicate tumors resistant to standard chemotherapy and for its potential contribution to tissue damage such as in ischemia/reperfusion. The center stage taken by phospholipid peroxidat...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.8b00349
更新日期:2019-03-18 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
pub_type: 杂志文章
doi:10.1021/tx400041v
更新日期:2013-07-15 00:00:00
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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::Exposure to both endogenous and exogenous formaldehyde has been established to be carcinogenic, likely by virtue of forming nucleic acid and proteins adducts such as N6-formyllysine. To better assess N6-formyllysine as a biomarker of formaldehyde exposure, we studied accumulation of N6-formyllysine adducts in tissues ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.7b00075
更新日期:2017-08-21 00:00:00
abstract::The toxic alpha,beta-unsaturated aldehyde acrolein readily attacks proteins, generating adducts at cysteine, histidine, and lysine residues. In this study, rabbit antiserum was raised against acrolein-modified keyhole limpet hemocyanin in the expectation that it would allow immunodetection of adducted proteins in biol...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0341106
更新日期:2003-10-01 00:00:00
abstract::Our laboratory previously reported the identification and quantification of depurinating DNA adducts of dibenzo[a,l]pyrene (DB[a,l]P) in vitro, which comprise about 84% of all the DNA adducts that are formed [Li, K.-M., et al. (1995) Biochemistry 34, 8043-8049]. To determine a complete adduct profile and identify both...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx980203p
更新日期:1999-09-01 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
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journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.8b00345
更新日期:2019-02-18 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
pub_type: 杂志文章
doi:10.1021/tx300282k
更新日期:2013-01-18 00:00:00
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journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400408x
更新日期:2014-04-21 00:00:00
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journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900259v
更新日期:2009-11-01 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
pub_type: 杂志文章
doi:10.1021/tx400156a
更新日期:2013-07-15 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::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
更新日期:2004-10-01 00:00:00
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journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx000178z
更新日期:2001-01-01 00:00:00
abstract::Methylglyoxal is a mutagenic bis-electrophile that is produced endogenously from carbohydrate precursors. Methylglyoxal has been reported to induce DNA-protein cross-links (DPCs) in vitro and in cultured cells. Previous work suggests that these cross-links are formed between guanine and either lysine or cysteine side ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500068v
更新日期:2014-06-16 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
pub_type: 杂志文章
doi:10.1021/tx3001576
更新日期:2012-08-20 00:00:00