Abstract:
:NADPH in microsomes reduces the hydroxocob(III)alamin form of vitamin B12 to cob(II)alamin and the supernucleophilic cob(I)alamin, which are both highly reactive toward xenobiotic epoxides formed by mammalian metabolism of dienes such as the industrially important chemicals chloroprene and 1,3-butadiene. With styrene, the metabolically formed styrene oxide is reactive toward cob(I)alamin but not cob(II)alamin. Such reactions in humans could lead to vitamin B12 deficiency, which is implicated in pernicious anemia, cancer, and degenerative diseases. However, glutathione inhibits the reduction of hydroxocob(III)alamin by formation of the 1:1 complex glutathionylcobalamin. This blocks reactions of the cobalamins with metabolically formed epoxides. The interaction between glutathione and vitamin B12 could protect against diseases related to vitamin B12 depletion.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Watson WP,Munter T,Golding BTdoi
10.1021/tx0497898subject
Has Abstractpub_date
2004-12-01 00:00:00pages
1562-7issue
12eissn
0893-228Xissn
1520-5010journal_volume
17pub_type
杂志文章abstract::N-Nitrosopyrrolidine (NPYR) is a well-established hepatocarcinogen in the rat. NPYR requires metabolic activation by cytochrome P450-catalyzed alpha-hydroxylation to express its carcinogenic activity. This produces alpha-hydroxyNPYR (2), which spontaneously ring opens to 4-oxobutanediazohydroxide (4), a highly reactiv...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx600332p
更新日期:2007-04-01 00:00:00
abstract::Anxiolytic kava products have been associated with rare but severe hepatotoxicity in humans. This adverse potential has never been captured in animal models, and the responsible compound(s) remains to be determined. The lack of such knowledge greatly hinders the preparation of a safer kava product and limits its benef...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5003194
更新日期:2014-10-20 00:00:00
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journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx200373u
更新日期:2012-01-13 00:00:00
abstract::Retinyl palmitate (RP) is frequently used as an ingredient in cosmetics and other retail products. We previously reported that, under UVA light irradiation, RP is facilely decomposed into multiple products, including anhydroretinol (AR) and 5,6-epoxyretinyl palmitate (5,6-epoxy-RP). We also determined that combined tr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0600907
更新日期:2006-11-01 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::Mitomycin C (MC), a cytotoxic anticancer drug and bifunctional DNA DNA alkylating agent, induces cross-linking of the complementary strands of DNA. The DNA interstrand cross-links (ICLs) are thought to be the critical cytotoxic lesions produced by MC. Decarbamoyl mitomycin C (DMC) has been regarded as a monofunctional...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx020044g
更新日期:2002-11-01 00:00:00
abstract::The Escherichia coli NarI restriction enzyme recognition site 5'G1G2C3G4C5C63' is a mutational hotspot for -2 deletions in E. coli plasmid pBR322, resulting in the sequence 5'GGCC3' when G4 is modified by the aromatic amine N-2-(acetyl)aminofluorene (AAF) [Burnouf, D., Koehl, P., and Fuchs, R. P. P. (1995) Proc. Natl....
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx980106w
更新日期:1998-11-01 00:00:00
abstract::The Adverse Outcome Pathway (AOP) paradigm details the existing knowledge that links the initial interaction between a chemical and a biological system, termed the molecular initiating event (MIE), through a series of intermediate events, to an adverse effect. An important example of a well-defined MIE is the formatio...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00099
更新日期:2016-06-20 00:00:00
abstract::3-Chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF) is a strong direct acting bacterial mutagen found in chlorine-disinfected drinking water. We studied the reaction of CMCF with 2-deoxyadenosine in buffered aqueous solutions and found that three main adducts were formed. The adducts were isolated and purified b...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx990116c
更新日期:1999-12-01 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.7b00184
更新日期:2017-10-16 00:00:00
abstract::Chemically reactive species formed from the metabolism of carboxylic acid-containing compounds have been proposed as mediators of their toxic side-effects. Two alternative metabolic pathways known to be involved in the generation of reactive acylating metabolites of carboxylic acids are acyl glucuronidation and acyl-C...
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::2,4-Dichlorophenol (2,4-DCP), an environmental pollutant, was reported to cause hepatotoxicity. The biochemical mechanisms of 2,4-DCP induced liver injury remain unknown. The present study showed that 2,4-DCP is chemically reactive and spontaneously reacts with GSH and bovine serum albumin to form GSH conjugates and B...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00118
更新日期:2020-09-21 00:00:00
abstract::Thiol conjugates of isothiocyanates (thiol-ITCs) are metabolites of ITCs formed in the mercapturic acid pathway in mammals. They are effective chemopreventive agents in mouse lung tumor bioassays and in other models. Thiol-ITCs are inhibitors of P450s, but it has not been determined if P450 inhibition is due to conjug...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx010029w
更新日期:2001-09-01 00:00:00
abstract::Pentachlorophenol (PCP) was shown to function as a reducing substrate for horseradish peroxidase (HRP) and to stimulate the HRP-catalyzed reduction of 5-phenyl-4-penten-1-yl hydroperoxide (PPHP) to 5-phenyl-4-penten-1-ol. HRP catalyzed the hydroperoxide-dependent oxidation of PCP, using H2O2, PPHP, or ethyl hydroperox...
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
abstract::2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic aromatic amine that is formed during the cooking of meats. PhIP is a potential human carcinogen: it undergoes metabolic activation to form electrophilic metabolites that bind to DNA and proteins, including serum albumin (SA). The structures of Ph...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300253j
更新日期:2012-10-15 00:00:00
abstract::A transient energy impairment with resultant release and subsequent reuptake of 5-hydroxytryptamine (5-HT) and NMDA receptor activation with consequent cytoplasmic superoxide (O(2)(-)(*)), nitric oxide (NO(*)), and peroxynitrite (ONOO(-)) generation have all been implicated in a neurotoxic cascade which ultimately lea...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx020029b
更新日期:2002-10-01 00:00:00
abstract::The reaction of chromium(VI) with hydrogen peroxide was studied in the presence of glutathione. In vitro, reaction of chromium(VI) with hydrogen peroxide alone led to production of hydroxyl radical as the significant reactive intermediate, while reaction of chromium(VI) with glutathione led to formation of two chromiu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00018a016
更新日期:1990-11-01 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:2000-05-01 00:00:00
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更新日期:2011-12-19 00:00:00
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更新日期:1996-04-01 00:00:00
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更新日期:2011-10-17 00:00:00
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更新日期:2002-09-01 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:2017-10-16 00:00:00
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更新日期:2001-09-01 00:00:00
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更新日期:2011-11-21 00:00:00
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更新日期:2015-03-16 00:00:00
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更新日期:2007-12-01 00:00:00
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更新日期:2001-04-01 00:00:00
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更新日期:1994-11-01 00:00:00