Abstract：
:Understanding the molecular basis of inorganic chemical toxicity has lagged behind the proliferation of detailed mechanisms that explain the biochemical toxicology of many organic xenobiotics. In this perspective, general barriers to explicating the bioinorganic chemistry of toxic metals are considered, followed by a detailed examination of these issues in relation to the toxicology of Cd2+. The hypothesis is evaluated that Cd2+ damages cells by replacing Zn2+ in key Zn proteins. An emerging methodology to assess the speciation of metals among cell proteins is described. Then, a more general hypothesis is suggested, namely, that the Zn proteome is also the toxicological target of other metals such as Pb2+ as well as NO and reactive oxygen species. The latter may damage cells by altering the structure and function of Zn2+ binding sites that include thiol ligands. In the process, labilized Zn2+ may also perturb cell biochemistry. Lastly, reactions of metal chelating ligands with the Zn proteome, including formation of ligand-Zn protein adducts, provide other potential avenues of biochemical toxicity.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Petering DHdoi
10.1021/acs.chemrestox.6b00328subject
Has Abstractpub_date
2017-01-17 00:00:00pages
189-202issue
1eissn
0893-228Xissn
1520-5010journal_volume
30pub_type
杂志文章abstract：:To reveal the roles of Y family DNA polymerases in the mutagenesis induced by oxidatively damaged DNA precursors, 2-hydroxy-dATP (2-OH-dATP) and 8-hydroxy-dGTP (8-OH-dGTP) were introduced into Escherichia coli strains deficient in the Y family polymerases, DNA polymerase IV (pol IV, encoded by the dinB gene) and DNA p...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx050046b
更新日期：2005-08-01 00:00:00
abstract：:Aryl radicals can react at the C8-site of 2'-deoxyguanosine (dG) to produce DNA adducts with a C8-C linkage (denoted C-linked). Such adducts are structurally distinct from those possessing a flexible amine (N-linked) or ether (O-linked) linkage, which separates the C8-aryl moiety from the guanine nucleobase. In the cu...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00233
更新日期：2015-08-17 00:00:00
abstract：:Hexavalent chromium is a human carcinogen activated primarily by direct reduction with cellular ascorbate and to a lesser extent, by glutathione. Cr(III), the final product of Cr(VI) reduction, forms six bonds allowing intermolecular cross-linking. In this work, we investigated the ability of Cr(VI) to cause interstra...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx400293s
更新日期：2013-10-21 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx1000283
更新日期：2010-05-17 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx700434v
更新日期：2008-04-01 00:00:00
abstract：:Purine deoxyribonucleoside 3'-phosphates were reacted separately with the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide. Products resulting from the cis and trans opening of the epoxide ring by the exocyclic amino groups of deoxyadenosine and deoxyguanosine 3'-phosphates were separat...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00029a015
更新日期：1992-09-01 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.9b00327
更新日期：2020-01-21 00:00:00
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 cu...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00009a006
更新日期：1989-05-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00424
更新日期：2015-12-21 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
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00398
更新日期：2016-06-20 00:00:00
abstract：:Prodrugs of 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine (90CE) are promising anticancer agents. The 90CE moiety is a readily latentiated, short-lived (t1/2 ∼ 30 s) chloroethylating agent that can generate high yields of oxophilic electrophiles responsible for the chloroethylation of the O-6 position of guanine ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx500197t
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/tx970170y
更新日期：1998-06-01 00:00:00
abstract：:Cholyl adenylate is a putative intermediate for biosynthesis of cholic acid-coenzyme A (CoA) thioester conjugates by acyl-CoA synthetase. Early studies showed the conjugated acid anhydride moiety of cholyl adenylate to be reactive, attacking proteins to form protein-cholic acid adducts. In the present study, to clarif...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx050159v
更新日期：2005-11-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00371
更新日期：2019-04-15 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00392
更新日期：2020-02-17 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9002808
更新日期：2010-03-15 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx8001737
更新日期：2008-08-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00013a004
更新日期：1990-01-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00029a003
更新日期：1992-09-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0256174
更新日期：2002-12-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00046a014
更新日期：1995-06-01 00:00:00
abstract：:The bay region epoxide of benzo[a]pyrene (anti-BPDE) alkylates DNA to form adducts with >98% trans stereochemistry. Halide ions catalyze this reaction; however, this pathway is characterized by the formation of adducts with altered cis stereochemistry. Bay region halohydrins are possible intermediates in these reactio...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx980056v
更新日期：1998-09-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9700073
更新日期：1997-06-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.7b00196
更新日期：2017-10-16 00:00:00
abstract：:The environmental contaminant benzo[c]phenanthrene (B[c]Ph) has weak carcinogenic activity in rodent bioassays; however, the fjord region diol epoxides of B[c]Ph, B[c]Ph-3,4-diol 1,2-epoxides (B[c]PhDE), are potent carcinogens. To determine the role of cytochrome P450 isozymes in the activation of B[c]Ph in MCF-7 cell...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx960174n
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/acs.chemrestox.9b00372
更新日期：2020-03-16 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx500377b
更新日期：2015-04-20 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00035a007
更新日期：1993-09-01 00:00:00
abstract：:To prevent the accumulation of reactive oxygen species and limit associated damage to biological macromolecules, cells express a variety of oxidant-detoxifying enzymes, including peroxiredoxins. In Saccharomyces cerevisiae, the peroxiredoxin Tsa1 plays a key role in peroxide clearance and maintenance of genome stabili...
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
