Abstract:
:The efficacy of 3-tert-butyl-4-hydroxyanisole (BHA) as a chemopreventive agent against chemically induced cancer or toxicity may involve the direct modulation of cytochrome P-450 dependent monooxygenase function. This hypothesis was investigated by using purified rabbit cytochrome P-450IA2 and P-450IIB4 in a reconstitution system with purified NADPH:cytochrome P-450 oxidoreductase and L-alpha-dilauroylphosphatidylcholine. BHA caused a concentration-dependent decrease in cytochrome P-450IIB4 dependent 7-ethoxycoumarin O-deethylation, cyclohexane hydroxylation, and benzphetamine N-demethylation activities (IC50; 28, 75, and 290 microM, respectively) and in cytochrome P-450IA2 dependent 7-ethoxyresorufin O-deethylation and acetanilide para hydroxylation activities (IC50 approximately 225 microM). The inhibition of monooxygenation activity was accompanied by redox cycling due to the tert-butylquinone produced during BHA metabolism, as measured by increased NADPH and oxygen consumption or hydrogen peroxide and superoxide anion production. Glutathione was shown to reverse this redox cycling phenomenon but did not reverse the BHA-dependent inhibition of monooxygenation activity. Using standard steady-state kinetic analyses, BHA was shown to be a mixed-type competitive inhibitor of benzphetamine metabolism by cytochrome P-450IIB4, suggesting that BHA does not simply compete as an alternate substrate for the hemoprotein but must also bind to another catalytically functional form of cytochrome P-450. BHA was shown to bind as a ligand to both purified and microsomal cytochrome P-450IA2, resulting in a low to high (type I) spin-state perturbation.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Rodrigues AD,Fernandez D,Nosarzewski MA,Pierce WM Jr,Prough RAdoi
10.1021/tx00021a004subject
Has Abstractpub_date
1991-05-01 00:00:00pages
281-9issue
3eissn
0893-228Xissn
1520-5010journal_volume
4pub_type
杂志文章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
abstract::Chemical respiratory sensitization is an immunological process that manifests clinically mostly as occupational asthma and is responsible for 1 in 6 cases of adult asthma, although this may be an underestimate of the prevalence, as it is under-diagnosed. Occupational asthma results in unemployment for roughly one-thir...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00320
更新日期:2020-12-15 00:00:00
abstract::The present work aimed to elucidate whether the toxic effects of nickel oxide (NiO) nanoparticles (NPs) on the yeast Saccharomyces cerevisiae were associated with oxidative stress (OS) and what mechanisms may have contributed to this OS. Cells exposed to NiO NPs accumulated superoxide anions and hydrogen peroxide, whi...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00022
更新日期:2018-08-20 00:00:00
abstract::n-Hexane is metabolized to the gamma-diketone 2,5-hexanedione (2,5-HD), a derivative that covalently binds to lysine residues in neurofilament (NF) protein to yield 2,5-dimethylpyrrole adducts. Studies comparing the pyrrole-forming potential and neurotoxic potency of gamma-diketones have demonstrated that pyrrolylatio...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00047a017
更新日期:1995-07-01 00:00:00
abstract::Chloroprene (2-chloro-1,3-butadiene, 1) is an important industrial chemical, which is carcinogenic in experimental animals and possibly in humans. It is metabolized to the monoepoxides, 2-chloro-2-ethenyloxirane (2a,b) and (1-chloroethenyl)oxirane (3a,b), together with electrophilic chlorinated aldehydes and ketones. ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx034107m
更新日期:2003-10-01 00:00:00
abstract::A new method was developed to quantify the levels of 1,3-butadiene (BD), butadiene monoxide (BDO), and butadiene diepoxide (BDO2) in blood. The method was based on vacuum distillation of tissues followed by analysis of the distillates using multidimensional GC/MS. Metabolites isolated from blood by vacuum distillation...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00044a002
更新日期:1995-03-01 00:00:00
abstract::Thioredoxin reductase (TR), an NADPH-dependent flavoenzyme that catalyzes the reduction of many disulfide-containing substrates, plays an important role in the cellular response to oxidative stress. Trivalent arsenicals, especially methyl As that contains trivalent arsenic (MAs(III)), are potent noncompetitive inhibit...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0001878
更新日期:2001-03-01 00:00:00
abstract::Capillary liquid chromatography/microelectrospray mass spectrometry has been applied to the detection of deoxyribonucleoside adducts of the food-derived mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) from in vitro and in vivo sources. Constant neutral loss (CNL) and selective reaction monitoring (SRM) techniques...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx990060m
更新日期:1999-10-01 00:00:00
abstract::Nicking of the DNA strand immediately upstream of an internal abasic (AP) site produces 5'-terminal abasic (dRp) DNA. Both the intact and the nicked abasic species are reactive intermediates along the DNA base excision repair (BER) pathway and can be derailed by side reactions. Aberrant accumulation of the 5'-terminal...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.7b00057
更新日期:2017-06-19 00:00:00
abstract::The microsomal metabolism of the carcinogen N-nitrosodimethylamine (NDMA) was suggested to be initiated by hydrogen atom abstraction to form an alpha-nitrosamino radical, which either oxidizes further to an alpha-hydroxy nitrosamine as the initial product of the activating dealkylation pathway or fragments to the nitr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00010a006
更新日期:1989-07-01 00:00:00
abstract::Smokeless tobacco products, such as moist snuff or chewing tobacco, contain many of the same carcinogens as tobacco smoke; however, the impact on children of indirect exposure to tobacco constituents via parental smokeless tobacco use is unknown. As part of the California Childhood Leukemia Study, dust samples were co...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00040
更新日期:2015-05-18 00:00:00
abstract::Divinyl sulfone (DVS) is an important oxidative metabolic product of sulfur mustard (SM) in vitro and in vivo. Although DVS is not a classical blister agent, its high reactivity and toxicity induced by vinyl groups can also cause blisters like SM upon contact with the skin, eyes, and respiratory organs. The purpose of...
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::Many organic sulfides (mono-, di-, and polysulfides) are present in our environment. Simple derivatives are produced by some plants and animals, while complex sulfides are secondary metabolites of several genera of bacteria and fungi. Sulfides play an important role in the smell and taste of food, and many such compou...
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::Troglitazone (TGZ), a 2,4-thiazolidinedione antidiabetic, causes hepatotoxicity in 1.9% of patients. TGZ is an inducer of, and substrate for, hepatic P450 3A. Microsomal metabolism yields a benzoquinone (TGZQ) and reactive intermediates. Kassahun et al. [Kassahun et al. (2001) Chem. Res. Toxicol. 14, 62-70] have trapp...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0001981
更新日期:2001-08-01 00:00:00
abstract::The activity of three metabolically activated methylating agents, N-methyl-N-(acetoxymethyl)nitrosamine (DMN-OAc), methylnitrosourethane (MNUT), and (methylazoxy)methanol acetate (MAM-Ac), were determined in cell culture by using a P388 cell growth rate inhibition assay. Experiments were conducted with normal P388 cel...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00011a004
更新日期:1989-09-01 00:00:00
abstract::Tetrandrine, a bisbenzylisoquinoline alkaloid, has demonstrated promising pharmacologic activities. The alkaloid has a great potential for clinical use, so a careful, thorough toxicity evaluation of the alkaloid is required. In the present study, 24 h acute toxicity of tetrandrine was evaluated in CD-1 mice. Single in...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200290s
更新日期:2011-12-19 00:00:00
abstract::Nitric oxide can be introduced slowly and steadily into aqueous solutions, including cell culture media, over extended periods of time via semipermeable Silastic (a registered trademark of the Dow Corning Corp.) polymer membranes. The rates of introduction are predictable and reproducible and can approach rates of nit...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00036a021
更新日期:1993-11-01 00:00:00
abstract::Experimental and epidemiological data associate the exposure of estrogens to cancer development in several tissues, particularly, the breast, endometrium, liver, and kidney. One plausible mechanism of estrogen-mediated carcinogenicity is DNA damage by redox cycling of estrogen catechols. Reports have shown that metabo...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200356v
更新日期:2012-02-20 00:00:00
abstract::3-(2-Deoxy-beta-D-erythro-pentofuranosyl)-6-hydroxy-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one is formed in low yield by the reaction of acrolein with 2'-deoxyguanosine. The nucleoside and an oligodeoxynucleotide containing it have been synthesized. For preparation of the nucleoside 2'-deoxyguanosine was alkyla...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx010181y
更新日期:2002-05-01 00:00:00
abstract::During our ongoing studies of the reactions of toluene diisocyanate (2,4- and 2,6-diisocyanatotoluene, TDI) in vivo, it became apparent that reactive form(s) of these diisocyanates reach(es) the circulatory system after passage through the respiratory system. Based on recent work by others regarding the transcarbamoyl...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960201+
更新日期:1997-04-01 00:00:00
abstract::Covalent binding of drug reactive metabolites to neutrophils or their precursors is thought to play a role in the development of drug-induced agranulocytosis. In this study, we used immunochemical techniques to compare the covalent binding of clozapine, vesnarinone, and procainamide (three drugs associated with agranu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx050095o
更新日期:2005-09-01 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::Contact allergy is caused by a wide range of chemicals after skin contact. Its clinical manifestation, allergic contact dermatitis (ACD), is developed upon repeated contact with the allergen. This perspective focuses on two areas that have yielded new useful information during the last 20 years: (i) structure-activity...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx7002239
更新日期:2008-01-01 00:00:00
abstract::N-Methyl-N-nitrosourea (MNU) is a reactive, mutagenic methylating agent. MNU methylates DNA at various sites, including guanine N7, guanine O6, and adenine N3. Dixit and Gold [(1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8039-8043] reported that ellagic acid, a phenolic natural product, inhibited the mutagenicity of MNU i...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00015a002
更新日期:1990-05-01 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::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::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
pub_type: 杂志文章
doi:10.1021/tx4003963
更新日期:2014-04-21 00:00:00
abstract::The PI3K/Akt/mTOR pathway is considered to be an attractive target for the development of novel anticancer molecules. This paper reports for the first time that a small molecule, antrocin (MW = 234), from Antrodia camphorata was a potent antagonist in various cancer types, being highest in metastatic breast cancer MDA...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx100318m
更新日期:2011-02-18 00:00:00
abstract::Quantitation of DNA adducts could provide critical information on the relationship between exposure to tobacco smoke and cancer risk in smokers. In this study, we developed a robust and sensitive liquid chromatography-tandem mass spectrometry method for the analysis of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasin...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300282k
更新日期:2013-01-18 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