Abstract:
:The genotoxicity of the dihydrofurans aflatoxin B1 (AFB1), aflatoxin G1 (AFG1), and sterigmatocystin (STG) was examined in a bacterial system in which the induction of SOS repair is monitored with the umuC gene linked to a lacZ reporter gene in plasmid pSK1002. Human liver microsomal cytochrome P-450NF oxidized the dihydrofurans (in the presence of calf thymus DNA) to give guanyl-N7 adducts in the order AFB1 greater than STG greater than AFG1. The order of the umu response seen was STG greater than AFB1 greater than AFG1, when either the dihydrofurans were activated enzymatically or the synthetic epoxides of the dihydrofurans were added directly to the bacteria. Thus, the umu response per molecule of guanyl-N7 DNA adduct follows the order STG greater than AFB1 greater than AFG1. A similar pattern has been reported in the literature for Salmonella typhimurium base substitution dependent his reversions, but the pattern AFB1 greater than STG greater than AFG1 has been found for bacterial frame-shift-dependent mutagenesis and hepatocarcinogenesis. The guanyl-N7 adduct derived from AFG1 has considerably less of all of these biological activities per molecule. Neither guanine imidazole ring opening nor apurinic site formation appears to be a factor involved in the differential biological responses seen with the three guanyl-N7 adducts. These findings indicate that these structurally related guanyl-N7 DNA adducts have intrinsic differences which give rise to divergent biological responses.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Baertschi SW,Raney KD,Shimada T,Harris TM,Guengerich FPdoi
10.1021/tx00008a008subject
Has Abstractpub_date
1989-03-01 00:00:00pages
114-2issue
2eissn
0893-228Xissn
1520-5010journal_volume
2pub_type
杂志文章abstract::4-Hydroxy-2-nonenal (HNE), a major electrophilic byproduct of lipid peroxidation, is mutagenic and cytotoxic. The two pairs of HNE-derived diastereomeric 1,N2-propanodeoxyguanosine 3'-monophosphate adducts were synthesized from reaction of HNE with 2'-deoxyguanosine 3'-monophosphate. After HPLC separation, these adduc...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
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更新日期:1997-11-01 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
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abstract::Nickel(II) compounds are established human carcinogens, but the molecular mechanisms underlying their activity are only partially known. One mechanism may include mediation by nickel of promutagenic oxidative DNA damage that depends on Ni(II) binding to chromatin. To characterize such binding at the histone moiety of ...
journal_title:Chemical research in toxicology
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doi:10.1021/tx00047a007
更新日期:1995-07-01 00:00:00
abstract::p,p'-DDE, the main metabolite of DDT, is notorious for its persistent and bioaccumulation. It has detrimental effects on the nervous system, while the mechanism is unclear. We sought to investigate the mechanism of p,p'-DDE-induced neurocytic apoptosis in PC12 cells by cytoflow and screen the potential target gene by ...
journal_title:Chemical research in toxicology
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abstract::The diarrhetic shellfish toxin composition in the digestive glands of mussels from the northern Adriatic sea was investigated. Along with known yessotoxins, identified by comparison of their chromatographic and spectral properties with those reported in the literature, we isolated a new analogue of yessotoxin, 42,43,4...
journal_title:Chemical research in toxicology
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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
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journal_title:Chemical research in toxicology
pub_type: 杂志文章
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更新日期:1994-09-01 00:00:00
abstract::The metabolic fates of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its two-electron oxidation product, the 1-methyl-4-phenyl-2,3-dihydropyridinium species (MPDP+), have been examined in mouse brain and liver tissue fractions. Incubations of MPTP (50 microM and 1 mM) with mouse brain...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
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journal_title:Chemical research in toxicology
pub_type: 杂志文章
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更新日期:1996-01-01 00:00:00
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
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更新日期:2014-10-20 00:00:00
abstract::Cytochrome P-450 enzymes have been postulated to oxidize amines through a variety of mechanisms. One of the means of distinguishing among potential pathways involves the use of kinetic hydrogen isotope effects: low isotope effects are characteristic of aminium radical mechanisms while high values are consistent with h...
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
abstract::Human hemoglobin was alkylated with (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and then treated with aqueous (+/-)-3-amino-1,2-propanediol to convert alkylated carboxyl side chains to N-(2,3-dihydroxypropyl) amides. Tryptic peptides produced from the modified protein...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00021a016
更新日期:1991-05-01 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
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更新日期:2003-03-01 00:00:00
abstract::The tumorigenic activity of manufactured gas plant residue (MGP) was evaluated in female A/J mice using a F0927 basal gel diet system. Adulterated diets containing MGP (0.10% or 0.25%) or benzo[a]pyrene (B[alpha]P; 16 or 98 ppm) were fed for 260 days. A negative control group was maintained on a nonadulterated basal g...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00049a008
更新日期:1995-10-01 00:00:00
abstract::Basic research, exploring the hypothesis that 2-(ω-carboxyethyl)pyrrole (CEP) modifications of proteins are generated nonenzymatically in vivo is delivering a bonanza of molecular mechanistic insights into age-related macular degeneration, autism, cancer, and wound healing. CEPs are produced through covalent modificat...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx200206v
更新日期:2011-11-21 00:00:00
abstract::Lapatinib (LAP), an oral tyrosine kinase inhibitor for the treatment of metastatic breast cancer, has been associated with idiosyncractic hepatotoxicity. Recent investigations have implicated the importance of P450 3A4/5 enzymes in the formation of an electrophilic quinone imine (LAPQI) metabolite generated through fu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00524
更新日期:2016-05-16 00:00:00
abstract::The clinical use of the immunosuppressant calcineurin inhibitor cyclosporine is limited by its nephrotoxicity. This is enhanced when combined with the immunosuppressive mTOR inhibitor sirolimus. Nephrotoxicity of both drugs is not yet fully understood. The goal was to gain more detailed mechanistic insights into the t...
journal_title:Chemical research in toxicology
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更新日期:2009-01-01 00:00:00
abstract::N'-Nitrosonornicotine (NNN) and N-nitrosopiperidine (NPIP) are potent esophageal and nasal cavity carcinogens in rats and pulmonary carcinogens in mice. N-Nitrosopyrrolidine (NPYR) induces mainly liver tumors in rats and is a weak pulmonary carcinogen in mice. These nitrosamines may be causative agents in human cancer...
journal_title:Chemical research in toxicology
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更新日期:2005-01-01 00:00:00
abstract::The metabolic pathway of tetrodotoxin (TTX), a powerful and specific voltage-gated sodium channel blocker, has not been well-clarified either in TTX-poisoned patients or in puffer fish. 4-S-CysteinylTTX (4-CysTTX) was isolated from the liver of the puffer fish, Fugu pardalis, as the first adduct of TTX with thiol. The...
journal_title:Chemical research in toxicology
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journal_title:Chemical research in toxicology
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更新日期:1988-11-01 00:00:00
abstract::The initial step in the genesis of neuromelanin, a black polymeric pigment normally found in the cytoplasm of dopaminergic cell bodies in the substantia nigra (SN), is the autoxidation of dopamine (DA) to DA-o-quinone (1). In this investigation, it is demonstrated that in the presence of L-cysteine (CySH) o-quinone 1 ...
journal_title:Chemical research in toxicology
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更新日期:1996-06-01 00:00:00
abstract::N(6)-(2-Hydroxy-3-buten-1-yl)-2'-deoxyadenosine (N(6)-HB-dA I) and N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (N(6),N(6)-DHB-dA) are exocyclic DNA adducts formed upon alkylation of the N(6) position of adenine in DNA by epoxide metabolites of 1,3-butadiene (BD), a common industrial and environmental che...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00166
更新日期:2015-07-20 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::Thiacetazone (TAZ) and ethionamide (ETA) are, respectively, thiourea- and thioamide-containing second line antitubercular prodrugs for which there is an extensive clinical history of cross-resistance in Mycobacterium tuberculosis. EtaA, a recently identified flavin-containing monooxygenase (FMO), is responsible for th...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
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更新日期:2006-03-01 00:00:00
abstract::Quantum dots (QDs) are a novel class of inorganic fluorophores which are gaining widespread recognition as a result of their exceptional photophysical properties and their applications as a biomarker and in molecular biomedical imaging. The aim of this study was to evaluate the in vivo genotoxicity in mice exposed to ...
journal_title:Chemical research in toxicology
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更新日期:2011-05-16 00:00:00
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journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960002q
更新日期:1996-07-01 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:2015-04-20 00:00:00
abstract::Inhalation of environmental particulate matter (PM) is correlated with adverse health effects in humans, but gene products that couple detection with cellular responses, and the specific properties of PM that target different pathways, have not been fully elucidated. TRPA1 and V1 are two cation channels expressed by s...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
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更新日期:2011-06-20 00:00:00
abstract::Interstrand cross-links are minor components of the collection of products formed in DNA by ionizing radiation. Through their formation by other damaging agents, it is known that interstrand cross-links exert significant effects on replication and transcription. The structures of DNA interstrand cross-links produced a...
journal_title:Chemical research in toxicology
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更新日期:2007-11-01 00:00:00
abstract::Peroxynitrite (PN), a very reactive oxidant formed by the combination of superoxide and nitric oxide, appears to play a role in producing tissue damage in a number of inflammatory conditions. Pharmacological scavenging and decomposition of PN within these areas has therapeutic value in several tissue injury models. Re...
journal_title:Chemical research in toxicology
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更新日期:2000-04-01 00:00:00