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 to cause an 85% depletion of neostriatal dopamine. Intrastriatal microdialysis in the rat with the corresponding 4-benzyl-1-methylpyridinium ion BMP+ for 60 min, however, causes nerve terminal destruction similar to that observed following a 15-min perfusion with the 1-methyl-4-phenylpyridinium ion MPP+, the monoamine oxidase B (MAO-B) generated metabolite derived from MPTP. With the aid of purified beef liver MAO-B and synthetic standards, we observed the efficient and quantitative conversion of BMTP to the corresponding 2,3-dihydropyridinium intermediate BMDP+, which underwent further, but incomplete, oxidation to BMP+. These MPTP-type properties point to in vivo effects, such as pharmacokinetic parameters and/or alternative metabolic pathways, to account for BMTP's lack of neurotoxicity.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Naiman N,Rollema H,Johnson E,Castagnoli N Jrdoi
10.1021/tx00014a008subject
Has Abstractpub_date
1990-03-01 00:00:00pages
133-8issue
2eissn
0893-228Xissn
1520-5010journal_volume
3pub_type
杂志文章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：:DNA damage and mutations are a major primary cause of cancer. Chemical bombardment of DNA is a major contributor to DNA damage. The Division of Chemical Toxicology recently hosted a panel of researchers who provided updates on the field of chemical toxicology at the nexus of DNA damage and repair. ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00438
更新日期：2021-01-28 00:00:00
abstract：:On the basis of a large number of reports concerning the detection of lipid peroxidation products as biomarkers in human diseases, there is no doubt that their steady-state levels increase under pathophysiological states associated with oxidative stress. The key question is whether they play any causative roles. This ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx600304n
更新日期：2007-01-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0601861
更新日期：2007-01-01 00:00:00
abstract：:The syntheses of potentially important metabolites of benzo[b]naphtho[2,1-d]thiophene ([2,1]BNT)--trans-1,2-dihydroxy-1,2-dihydrobenzo[b]naphtho[2,1- d]thiophene ([2,1]BNT-1,2-diol) and trans-3,4-dihydroxy-3,4-dihydrobenzo[b]naphtho[2,1-d]thiophene ([2,1]BNT-3,4-diol)--are described. The syntheses involved preparation...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00014a002
更新日期：1990-03-01 00:00:00
abstract：:We have previously reported that mono- and dichlorinated biphenyls (PCBs) can be metabolized to dihydroxy compounds and further oxidized to reactive metabolites which form adducts with nitrogen and sulfur nucleophiles including DNA [Amaro et al. (1966) Chem. Res. Toxicol. 9, 623-629; Oakley et al. (1996) Carcinogenesi...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx960103o
更新日期：1996-12-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx800185b
更新日期：2008-09-01 00:00:00
abstract：:alpha-Sulfate trans-tamoxifen and alpha-sulfate cis-tamoxifen were synthesized as proposed active metabolites of tamoxifen that react with DNA. alpha-Acetoxytamoxifen was prepared as a model-activated form to produce a reactive carbocation. Calf thymus DNA was reacted with alpha-hydroxytamoxifen or the activated forms...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx960114h
更新日期：1997-02-01 00:00:00
abstract：:DNA-DNA cross-linking by 1,2,3,4-diepoxybutane (DEB) is considered the molecular basis for its potent cytotoxic and genotoxic effects. DEB reactions with DNA initially lead to N7-(2'-hydroxy-3',4'-epoxybut-1'-yl)-guanine monoadducts, which can then alkylate neighboring DNA bases to form bifunctional lesions. We recent...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx060204e
更新日期：2007-02-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00013
更新日期：2020-06-15 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/tx100276f
更新日期：2010-12-20 00:00:00
abstract：:Acrolein is a highly toxic environmental pollutant that readily alkylates the epsilon-amino group of lysine residues in proteins. In model systems, such chemistry involves sequential addition of two acrolein molecules to a given nitrogen, forming bis-Michael-adducted species that undergo aldol condensation and dehydra...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0502387
更新日期：2005-11-01 00:00:00
abstract：:Exposure to polychlorinated biphenyls (PCBs) has been implicated in adverse human health effects, including developmental neurotoxicity. Several neurotoxic PCBs are chiral and undergo atropisomeric enrichment in vivo due to atropselective metabolism by cytochrome P450 enzymes. Here we study how the liver-specific dele...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00389
更新日期：2019-04-15 00:00:00
abstract：:The synthesis, toxicity, neuroprotection, and human acetylcholinesterase (hAChE)/ human butyrylcholinesterase (hBuChE) inhibition properties of β-naphthotacrines1-14 as new drugs for Alzheimer's disease (AD) potential treatment, are reported. β-Naphthotacrines1-14 showed lower toxicity than tacrine; moreover, at the h...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx400138s
更新日期：2013-06-17 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx800268f
更新日期：2008-12-01 00:00:00
abstract：:Diclofenac sodium (DFS), a nonsteroidal anti-inflammatory drug, is frequently used in ophthalmology, but it causes negative effects on corneas. The mechanisms underlying the toxicities to corneas remains unclear. The present study was designed to assess the cytotoxicity of DFS to human corneal epithelial (HCEP) cells ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00319
更新日期：2021-01-18 00:00:00
abstract：:Genotoxic chemicals act by causing DNA damage, which, if left unrepaired, can have deleterious consequences for cell survival. DNA damage response (DDR) gets activated to repair or mitigate the effects of DNA damage. Histone H2AX and H3 phosphorylation biomarkers (γ-H2AX and p-H3) have attracted great attention as the...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00104
更新日期：2020-08-17 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx400147c
更新日期：2013-08-19 00:00:00
abstract：:The efficacy of DNA-damaging anticancer drugs is highly influenced by cellular DNA repair capacity, and by inhibiting the relevant DNA repair pathway, efficacy of alkylating agents may be increased. Therefore, combining DNA repair inhibitors with anticancer agents that selectively target tumor tissue should improve ca...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
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更新日期：2013-11-18 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx980122t
更新日期：1998-11-01 00:00:00
abstract：:Trichloroethylene (TCE), a widely used industrial solvent, is a common environmental contaminant. We previously reported that TCE-induced changes in DNA methylation and miRNA expression contributed to the development of a liver tumor in mice. In this study, we investigated the role of long intergenic noncoding RNA (Li...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00382
更新日期：2020-06-15 00:00:00
abstract：:This study was designed to distinguish and evaluate the contribution of reactive metabolite and reactive oxygen species as the mechanism of metabolism-dependent valproic acid-induced in vitro cytotoxicity. The involvement of reactive oxygen species in the mechanism of in vitro cytotoxicity was examined by the addition...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9801864
更新日期：1999-04-01 00:00:00
abstract：:Exposure to the tobacco-related nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine is carcinogenic to humans. Metabolic activation of NNK leads to the formation of DNA adducts, which play a critical role in NNK carcinogenesis. Adducts specific to NNK result from covalent linkag...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx050028u
更新日期：2005-06-01 00:00:00
abstract：:A liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) method for the measurement of aflatoxin biomarkers in urine has been developed and validated. The two major aflatoxin-DNA adducts formed in rat tissues, aflatoxin N(7)-guanine and its imidazole ring opened derivative, 8,9-dihydro-8-(2,6-diami...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx010063a
更新日期：2001-07-01 00:00:00
abstract：:Magnesium is directly involved in the control of cell growth and survival, but its role in cancer biology and therapy is multifaceted; in particular, it is highly controversial whether magnesium levels can affect therapy outcomes. Here we investigated whether magnesium availability can modulate cellular responses to t...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00478
更新日期：2016-03-21 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx600344a
更新日期：2007-03-01 00:00:00
abstract：:The chlorofluorocarbon substitute 1,2-dichloro-1,1-difluoroethane (HCFC-132b) undergoes oxidative metabolism in rats to give a range of metabolites, including chlorodifluoroacetaldehyde [Harris and Anders (1991) Chem. Res. Toxicol. 4, 180]. The present experiments were undertaken after studies to characterize an unide...
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：:Exposure to fine particulate matter (PM2.5), of which secondary organic aerosol (SOA) is a major constituent, is linked to adverse health outcomes, including cardiovascular disease, lung cancer, and preterm birth. Atmospheric oxidation of isoprene, the most abundant nonmethane hydrocarbon emitted into Earth's atmosphe...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00322
更新日期：2020-02-17 00:00:00
abstract：:Taconite mining involves potential exposure to non-asbestiform amphibole mineral fiber. More recent studies have demonstrated increased mortality from respiratory cancers and heart disease among workers in the taconite industry. This finding is not consistent with recent exposure assessment findings, nor is the toxico...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00472
更新日期：2016-02-15 00:00:00
abstract：:Cryogenic (4-10 K) laser-induced vibrationless ground state and vibronic excited state fluorescence emission spectra of the adducts resulting from reaction in vitro of human serum albumin and the carcinogen (+-)-r-7,t-8-dihydroxy-c-9,c-10-epoxy-7,8,9,10- tetrahydrobenzo[a]-pyrene were recorded in order to determine th...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00025a012
更新日期：1992-01-01 00:00:00
