Abstract:
:Previous work has shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes porphyria, enhanced by iron, in C57BL/6J mice with marked accumulation in the liver of uroporphyrin I and III isomers and heptacarboxylic acid III and is one model of human porphyria cutanea tarda. Preliminary examination by HPLC also indicated the presence of some oxygenated side chain uroporphyrin derivatives. Here, the porphyrin constituents of TCDD-induced porphyric liver have been examined by HPLC/electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC/ESI-Q-TOFMS) to characterize the major and minor porphyrins present in hepatic tissue. As well as the major constituents uroporphyrins I and III, we identified the isomers of heptacarboxylic, hexacarboxylic, and pentacarboxylic acid porphyrins arising from intermediates in the stepwise decarboxylation of uroporphyrinogen I and III to coproporphyrinogens. In addition, monohydroxy analogues of uroporphyrin isomers were detected hydroxylated in the acetic acid and beta-positions of propionic acid side chains and in the meso ring position. Of particular note, for the first time for human and experimental porphyrias, we found chlorins (dihydroxy-, hydroxyspirolactone- ,and dihydroxyspirolactone-urochlorins) consistent with those derived from an epoxyurochlorin structure, formed by oxidation of the double bond of a pyrrole ring of uroporphyrinogen I and III isomers. The findings demonstrate that oxygen insertion into the pyrrole rings of uroporphyrinogens occurs under pathological circumstances in vivo and support the evidence for an oxidative cellular environment present in TCDD-treated porphyric tissue.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Lim CK,Danton M,Clothier B,Smith AGdoi
10.1021/tx060212vsubject
Has Abstractpub_date
2006-12-01 00:00:00pages
1660-7issue
12eissn
0893-228Xissn
1520-5010journal_volume
19pub_type
杂志文章abstract::Glyoxal is generated endogenously from the degradation of glucose and the oxidation of carbohydrates, lipids, and the 2-deoxyribose moieties of DNA. Glyoxal is also widely used in industry and is present in cigarette smoke and food. Glyoxal can conjugate with nucleobases and proteins to give advanced glycation end pro...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900286c
更新日期:2010-01-01 00:00:00
abstract::N,N-Bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil, 1) is an orally administrated drug widely used in the chemotherapy of chronic lymphocytic leukemia. We have recently described a new metabolic path for the decomposition of 1 in human gastric juice based on its reactions with saliva-derived thiocyanate io...
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::A predominant pathway of xenobiotic-induced toxicity is initiated by bioactivation. Characterizing reactive intermediates will provide information on the structure of reactive species, thereby defining a potential bioactivation mechanism. Because most reactive metabolites are not stable, it is difficult to detect them...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200033v
更新日期:2011-05-16 00:00:00
abstract::We have previously reported that the diuretic thiosteroid spironolactone (SPL) inactivates rat liver microsomal cytochromes P450 [P450 (P450 3A and P450 2C11)] in a in a mechanism-based fashion, and we have identified two polar SPL metabolites (SPL-sulfinic acid and -sulfonic acid), formed in a partition ratio of appr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00024a012
更新日期:1991-11-01 00:00:00
abstract::Among the cellular components that can react directly with peroxynitrite in the presence of physiological CO(2) concentrations are sulfur-, selenium-, and metal-containing proteins, in particular hemoproteins. We have previously shown that the reactions of peroxynitrite with oxymyoglobin (MbFeO(2)) and oxyhemoglobin p...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx025595l
更新日期:2003-03-01 00:00:00
abstract::The carcinogen 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) alkylates DNA at dGuo, dAdo, and dCyd. dCyd adducts, formed in small amounts, elute near the more abundant dGuo adducts. We isolated the dCyd adducts formed with dCMP. Each BPDE enantiomer forms three major adducts with dCMP, two...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0340201
更新日期:2004-04-01 00:00:00
abstract::Skin protein modification (haptenation) is thought to be a key step in the manifestation of sensitization to low molecular mass chemicals (<500 g/mol). For sensitizing chemicals that are not protein reactive, it is hypothesised that metabolic activation can convert such chemicals into protein reactive toxins within th...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0341456
更新日期:2004-03-01 00:00:00
abstract::Water samples from the Waka River, which runs through an area housing many chemical industry facilities in Wakayama, Japan, have been found to show significant mutagenicity, especially without a mammalian metabolic activation system (S9 mix) in the Salmonella typhimurium YG1024 strain. Mutagens in the river water were...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx010163g
更新日期:2002-03-01 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
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::The C2'-oxidized abasic lesion (C2-AP) is produced in DNA that is subjected to oxidative stress. The lesion disrupts replication and gives rise to mutations that are dependent upon the identity of the upstream nucleotide. Ape1 incises C2-AP, but the 5'-phosphorylated fragment is not a substrate for the lyase activity ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9003984
更新日期:2010-04-19 00:00:00
abstract::The preparation and DNA binding characteristics of a structural analog of Hoechst 33258 bearing two pyridinic nitrogen atoms are described. The 1H NMR signals of the complex formed between the new ligand 1 and decadeoxyribonucleotide d(CATGGCCATG)2 were assigned by employing one- and two-dimensional NMR techniques. In...
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
abstract::The nuclear receptor human pregnane X receptor (hPXR) is a ligand-regulated transcription factor that responds to a wide range of endogenous and xenobiotic molecules. Upon activation with ligands, hPXR can increase induction levels of metabolic enzymes. Therefore, hPXR plays a critical role in drug metabolism and excr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200310j
更新日期:2011-10-17 00:00:00
abstract::PAHs (polycyclic aromatic hydrocarbons) are suspect lung cancer carcinogens that must be metabolically converted into DNA-reactive metabolites. P4501A1/P4501B1 plus epoxide hydrolase activate PAH to (+/-)- anti-benzo[ a]pyrene diol epoxide ((+/-)- anti-BPDE), which causes bulky DNA adducts. Alternatively, aldo-keto re...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700404a
更新日期:2008-05-01 00:00:00
abstract::Human hepatocellular carcinoma cells, HepG2, are often used for drug mediated mitochondrial toxicity assessments. Glucose in HepG2 culture media is replaced by galactose to reveal drug-induced mitochondrial toxicity as a marked shift of drug IC50 values for the reduction of cellular ATP. It has been postulated that ga...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00033
更新日期:2019-08-19 00:00:00
abstract::The purpose of this study was to investigate the degree of chlorination of catechol (CAT) derivatives of pentachlorophenol (PCP) on the induction of cytotoxicity and DNA damaging effects in calf thymus DNA (ct-DNA) and in two human breast carcinoma cell lines. Results indicated that with the addition of the transition...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0498511
更新日期:2005-02-01 00:00:00
abstract::The skeleton is a target organ for most metals. This leads to their bioaccumulation, either as storage of useful oligoelements or as a protection against damage by toxic elements. The different events leading to their accumulation in this organ, under constant remodeling, are not fully understood, nor the full subsequ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx300064m
更新日期:2012-06-18 00:00:00
abstract::The rat esophagus is strikingly sensitive to tumor induction by nitrosamines, and it has been hypothesized that this tissue contains cytochrome P450 enzymes (P450s) which catalyze the metabolic activation of these carcinogens. The metabolic capacity of the esophagus is not well characterized. In the study described he...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx010065v
更新日期:2001-10-01 00:00:00
abstract::Chemical and structural alterations to lysozyme (LYSO), glucose 6-phosphate dehydrogenase (G6PD), and bovine eye lens proteins (BLP) promoted by peroxyl radicals generated by the thermal decomposition of 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) under aerobic conditions were investigated. SDS-PAGE analysis of...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300372t
更新日期:2013-01-18 00:00:00
abstract::To investigate the biological effects of the O(2)-alkylthymidines induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), we have replicated a plasmid containing O(2)-methylthymidine (O(2)-Me-dT) or O(2)-[4-(3-pyridyl-4-oxobut-1-yl]thymidine (O(2)-POB-dT) in Escherichia coli w...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200435d
更新日期:2011-11-21 00:00:00
abstract::Cells respond to stress by controlling gene expression at several levels, with little known about the role of translation. Here, we demonstrate a coordinated translational stress response system involving stress-specific reprogramming of tRNA wobble modifications that leads to selective translation of codon-biased mRN...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00004
更新日期:2015-05-18 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
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
abstract::The site specifically modified oligonucleotides 5'-d(TCCTCCTG1G2CCTCTC) (I) and 5'-d(CTATG1G2G3TATC) (II) were synthesized with single modified guanine residues at positions G1, G2, or G3, derived from the covalent binding reaction of 7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ((+)-anti-BPDE) with ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9501086
更新日期:1996-01-01 00:00:00
abstract::1,2,3,4-Diepoxybutane (DEB) is a prominent carcinogenic metabolite of 1,3-butadiene (1,3-BD), an important industrial chemical and an environmental pollutant found in cigarette smoke and automobile exhaust. DEB is capable of inducing a variety of genotoxic effects, including point mutations, large deletions, and chrom...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0498206
更新日期:2004-12-01 00:00:00
abstract::The metabolism of genistein (4',5,7-trihydroxyisoflavone), a phytoestrogen derived from soy products, was investigated using rat and human liver microsomes and recombinant human cytochrome P450 enzymes. Metabolism of genistein by microsomes obtained from rats treated with pyridine, phenobarbital, beta-naphthoflavone, ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9802320
更新日期:1999-07-01 00:00:00
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::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::Cyadox is a novel derivative of quinoxaline-1,4-dioxides (QdNOs) with the potential to be developed as a feed additive. However, the pharmacological and toxicological bioactive molecules of cyadox and the molecular mechanism of its pharmacological and toxic actions remain unclear. In the present study, cyadox and its ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00194
更新日期:2018-11-19 00:00:00
abstract::8-Hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, has been extensively studied to assess human exposure to carcinogenic compounds. Previous studies have associated levels of human urinary hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) with those of 8-OHdG. However, measurements of OH-...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200517h
更新日期:2012-02-20 00:00:00