Abstract：
:Estrogen exposure through early menarche, late menopause, and hormone replacement therapy increases the risk factor for hormone-dependent cancers. Although the molecular mechanisms are not completely established, DNA damage by quinone electrophilic reactive intermediates, derived from estrogen oxidative metabolism, is strongly implicated. A current hypothesis has 4-hydroxyestrone-o-quinone (4-OQE) acting as the proximal estrogen carcinogen, forming depurinating DNA adducts via Michael addition. One aspect of this hypothesis posits a key role for NAD(P)H-dependent quinone oxidoreductase (NQO1) in the reduction of 4-OQE and protection against estrogen carcinogenesis, despite two reports that 4-OQE is not a substrate for NQO1. 4-OQE is rapidly and efficiently trapped by GSH, allowing measurement of NADPH-dependent reduction of 4-OQE in the presence and absence of NQO1. 4-OQE was observed to be a substrate for NQO1, but the acceleration of NADPH-dependent reduction by NQO1 over the nonenzymic reaction is less than 10-fold and at more relevant nanomolar concentrations of substrate is less than 2-fold. An alternative detoxifying enzyme, glutathione-S-transferase, was observed to be a target for 4-OQE, rapidly undergoing covalent modification. These results indicate that a key role for NQO1 and GST in direct detoxification of 4-hydroxy-estrogen quinones is problematic.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Chandrasena RE,Edirisinghe PD,Bolton JL,Thatcher GRdoi
10.1021/tx8000797subject
Has Abstractpub_date
2008-07-01 00:00:00pages
1324-9issue
7eissn
0893-228Xissn
1520-5010journal_volume
21pub_type
杂志文章abstract：:Although many phenols and catechols found as polyphenol natural products are antioxidants and have putative disease-preventive properties, others have deleterious health effects. One possible route to toxicity is the bioactivation of the phenolic function to quinones that are electrophilic, redox-agents capable of mod...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx200140s
更新日期：2011-09-19 00:00:00
abstract：:Many herbal medicines such as epimedium have been reported to cause adverse effects, and icaritin is the common aglycone of many glucosides in epimedium. Our present work aimed at the clarification of the metabolic activation of icaritin possibly responsible for the adverse effects of epimedium. A quinone methide meta...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00418
更新日期：2019-06-17 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx034066u
更新日期：2003-08-01 00:00:00
abstract：:Deoxyribose oxidation in DNA represents a biologically important facet of oxidative DNA damage that gives rise to protein-DNA cross-links and base adducts. Toward the goal of quantifying deoxyribose oxidation chemistry in cells, we report a method for the quantification of 3'-phosphoglycolaldehyde (PGA) residues, whic...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0341198
更新日期：2003-12-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
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更新日期：2015-05-18 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0155101
更新日期：2001-09-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00085
更新日期：2019-06-17 00:00:00
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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：:Estrogens, including the natural hormones estrone (E(1)) and estradiol (E(2)), are thought to be involved in tumor induction. Specifically, catechol estrogen quinones (CEQs) derived from the catechol estrogens 4-hydroxyestrone (4-OHE(1)) and 4-hydroxyestradiol (4-OHE(2)) react with DNA and form DNA adducts (Cavalieri,...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx020088p
更新日期：2003-03-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx970010m
更新日期：1997-05-01 00:00:00
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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
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00039a005
更新日期：1994-05-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/tx400183y
更新日期：2013-08-19 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx020008h
更新日期：2002-08-01 00:00:00
abstract：:Xenobiotics may activate the estrogen receptor, resulting in alteration of normal endocrine functions in animals and humans. Consequently, this necessitates development of assay end points capable of identifying estrogenic xenobiotics. In the present study, we screened the potential estrogenicity of chemicals via thei...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx5002089
更新日期：2014-08-18 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00346
更新日期：2019-03-18 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00001a008
更新日期：1988-01-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00104
更新日期：2018-07-16 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx500341z
更新日期：2015-01-20 00:00:00
abstract：:A newly developed recombinant yeast strain, in which the human estrogen receptor has been stably integrated into the genome of the yeast, was used to gain information on the estrogenic activity of a large series of dietary flavonoids. Among 23 flavonoids investigated, 8 were found to markedly stimulate the transcripti...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx970170y
更新日期：1998-06-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00045a005
更新日期：1995-04-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0155956
更新日期：2002-05-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx7002905
更新日期：2008-02-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00518
更新日期：2016-04-18 00:00:00
abstract：:The efficacy of 3-tert-butyl-4-hydroxyanisole (BHA) as a chemopreventive agent against chemically induced cancer or toxicity may involve the direct modulation of cytochrome P-450 dependent monooxygenase function. This hypothesis was investigated by using purified rabbit cytochrome P-450IA2 and P-450IIB4 in a reconstit...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00021a004
更新日期：1991-05-01 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/tx700425n
更新日期：2008-03-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00014a013
更新日期：1990-03-01 00:00:00
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
更新日期：2008-07-01 00:00:00
abstract：:Oxidative stress is associated with the pathophysiology of many degenerative human diseases, including Alzheimer's disease, atherosclerosis, Parkinson's disease, and cancers. We discovered in our previous study that thioproline (SPro), a proline analogue, is generated in oxidant-exposed cells. With the prior observati...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00055
更新日期：2020-07-20 00:00:00
