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1.
The involvement of a non-'bay-region' diol-epoxide in the formation of benz(a)anthracene-DNA adducts in a rat-liver microsomal system 总被引:1,自引:0,他引:1
A D MacNicoll C S Cooper O Ribeiro P G Gervasi A Hewer C Walsh P L Grover P Sims 《Biochemical and biophysical research communications》1979,91(2):490-497
The metabolic activation of benz(a)anthracene was investigated by incubating [3H]-benz(a)anthracene with DNA, a NADPH-generating system and rat-liver microsomes. When hydrolysates of the DNA were chromatographed on Sephadex LH20 columns, three hydrocarbon-nucleoside adduct peaks were resolved and these were further examined using HPLC. One adduct probably results from the reaction of the non-bay-region diol-epoxide -8,-9-dihydroxy--10,11-oxy-8,9,10,11-tetrahydrobenz(a)anthracene -BA-8,9-diol 10,11-oxide) with DNA. The other two adducts did not co-chromatograph with adducts formed from any of the four possible isomeric diolepoxides that can be formed in the 8,9,10,11-ring of benz(a)anthracene. 相似文献
2.
D H Swenson J A Miller E C Miller 《Biochemical and biophysical research communications》1973,53(4):1260-1267
Fortified hamster and rat liver microsomes bind the carcinogen aflatoxin B1 (AFB1), but not its much less carcinogenic 2,3-dihydro derivative (aflatoxin B2), to RNA in vitro. Mild acid hydrolysis of the RNA-AFB1 adduct yields a product indistinguishable from synthetic 2,3-dihydro-2,3-dihydroxy-AFB1 in (a) its UV absorption spectra in neutral and alkaline solution, (b) its thin layer chromatography in several solvent systems, and (c) the mass spectra of the acetonide and diacetyl derivatives. AFB1-2,3-oxide is the probable reactive precursor of the RNA-AFB1 adduct. This epoxide merits consideration as a candidate ultimate carcinogenic metabolite of AFB1. 相似文献
3.
14C-Sterigmatocystin isolated from cultures of supplemented with (1-14C)acetate was shown to be efficiently converted to aflatoxin B1 by the resting mycelium of . The experimental results may indicate a biosynthetic pathway leading from 5-hydroxysterigmatocystin to sterigmatocystin and then to aflatoxin B1. 相似文献
4.
Comparative metabolic conversion of aflatoxin B1 to M1 and Q1 by monkey, rat and chicken liver 总被引:1,自引:0,他引:1
We studied the metabolish of flatoxin B1 by liver microsomal preparations from monkey, rat and chicken. With all these species, both the previously recognized metabolite aflatoxin M1 as well as the newly identified aflatoxin Q1 were produced from the aflatoxin B1 substrate. Aflatoxin Q1 is an isomer of aflatoxin M1 (with the hydroxyl on the carbon β to the carbonyl of the cyclopentenone ring) which we discovered recently in rat and monkey liver incubations with aflatoxin B1. In our incubations we did not detect aflatoxin P1 which has been reported as a major metabolite of aflatoxin B1 in the monkey.In general the conversion to aflatoxin M1 was comparable among the different species (1–3% of the substrate) except in the chicken in which it was lower (0.1–0.3%). Also the conversion to Q1 was comparable to or slightly higher than the conversion to M1 with rat and chicken liver but the conversion to Q1 with the monkey liver was outstandingly high, accounting for 19–52% of the substrate in three species of monkeys tested. 相似文献
5.
R E Catalán M P Castillón V G Corces C Avila 《Biochemical and biophysical research communications》1977,74(1):279-284
The cytochrome P-450 content of primary hepatocyte cultures was maintained at levels close to those found by using a defined medium containing testosterone, thyroxine, hydrocortisone, estradiol, glucagon, insulin, linoleic acid and oleic acid. Using these cultures, [14C]aflatoxin B1, a potent liver carcinogen, was metabolized primarily to water-soluble metabolites. In agreement with results, aflatoxin M1 was the only nonpolar metabolite detected. In addition, a significant portion of radioactivity was covalently bound to cell constituents. These results suggest that primary hepatocyte cultures may be a good model of the liver for studying the metabolism and mechanism of action of toxic chemicals. 相似文献
6.
B F Coles J R Smith R C Garner 《Biochemical and biophysical research communications》1977,76(3):888-892
Racemic 3a,8a-dihydrofuro[2,3-b]benzofuran has been chemically synthesized as a model of the vinyl ether structure of aflatoxin B1 (AFB1) and tested for mutagenicity. In the presence of 9000g rat liver supernatant fraction the compound induced his+ revertant colonies in TA 100 but with only one five-thousandth the activity of AFB1. No mutagenicity was found when strain TA98 was used. Omission of the rat liver preparation abolished mutagenic activity. The reduced compound, tetrahydrofurobenzofuran, was inactive as a mutagen either in the presence or absence of the rat liver supernatant. 相似文献
7.
Sun-Shine Yuan 《Steroids》1982,39(3):279-289
A-ring enollactones , or derived from 4-cholesten-3-one, testosterone benzoate or 3-oxo-4-estren-17β-yl benzoate were condensed with [1,2-13C2]acetyl chloride to give intermediates , or . and were cyclized by acid or base to give 3,4-13C2-labeled 4-cholesten-3-one and testosterone, respectively. [3,4-13C2]4-Cholesten-3-one was converted via reduction of its trimethylsilyl enol ether to [3,4-13C2]cholesterol. Acetyl enollactone was cyclized in acetic acid to [3,4-13C2]3-oxo-4-estren-17β-yl benzoate followed by aromatization and hydrolysis to produce [3,4-13C2]estradiol-17β. Alternatively, cyclization of with base afforded [3,4-13C2]3-oxo-4-estren-17β-ol directly, which was then oxidized and aromatized to yield [3,4-13C2]estrone. Ozonolysis of progesterone, conversion to the diketal ester and acylation followed by acid hydrolysis furnished [3,4-13C2]progesterone. 相似文献
8.
A nuclear exoribonuclease from Novikoff ascites cells was used to study the hydrolysis of single-stranded heteropolymers containing [14C]adenylic acid and either uridylic acid or cytidylic acid and heteropolymers of [14C]adenylic acid and one of the corresponding 2′--methylated nucleotides. The results of these studies indicate that both the rate and extent of hydrolysis are greatly inhibited by the presence of 2′--methylated nucleotides. Restriction of exonuclease activity by 2′--methylated nucleotides provides a possible mechanism for rRNA processing. 相似文献
9.
Avermectin B1a, an antihelminthic macrocyclic lactone, has been previously shown to reduce muscle membrane resistance by stimulating γ-aminobutyric acid-mediated chloride conductance. Since the benzodiazepine receptor is coupled to a receptor for γ-aminobutyric acid and related chloride ionophore, the effects of Avermectin B1a on [3H]diazepam binding to the benzodiazepine receptor were studied. In well-washed membrane fragments from rat cerebral cortex, Avermectin B1a markedly increased the binding of [3H]diazepam to benzodiazepine receptors. This effect was qualitatively similar to that observed with either γ-aminobutyric acid or chloride ion and was partially reversed by the γ-aminobutyric acid receptor antagonist, bicuculline. In contrast to the effects of γ-aminobutyric acid and chloride, the enhanced binding of [3H]benzodiazepine elicited by Avermectin B1a was reversed by extensive washing of the membrane preparation. Avermectin B1a appears to irreversibly modify benzodiazepine receptors at a γ-aminobutyric acid-chloride recognition site and may be valuable in biochemical studies of the regulation of benzodiazepine receptor function. 相似文献
10.
Thomas W. Kensler William F. Busby Nancy E. Davidson Gerald N. Wogan 《Biochimica et Biophysica Acta (BBA)/General Subjects》1976,437(1):200-210
The effect of aflatoxin B1 on the binding capacity of rat liver cytoplasmic glucocorticoid receptors and the nuclear binding of the activated receptor complex was investigated. No alterations in the kinetics of [3H]dexamethasonccytosol receptor complex formation were noted 2 h after treatment with 1 mg/kg aflatoxin B1. However, a 33% decrease in the concentration of nuclear acceptor sites and a 24% decrease in the glucocorticoid receptor-nuclear binding equilibrium constant of dissociation was observed. This response was near maximal at 2 h and persisted for at least 36 h. Inhibition of nuclear binding capacity was directly related to aflatoxin B1 dose, with a correlation coefficient of 0.99. Actinomycin D treatment (0.1 mg/kg) resulted in a slight reduction (16%) in the concentration of nuclear acceptor sites but had no effect on the nuclear binding dissociation constant.Administration of [3H]dexamethasone to aflatoxin B1-treated rats produced a similar pattern of glucocortocoid binding distribution in vivo to that observed in vitro. No differences in [3H]dexamethasone-cytoplasmic receptor binding between control and aflatoxin B1-treated rats were found, whereas nuclear [3H]dexamethasone binding was reduced 34% by aflatoxin B1 treatment. 相似文献
11.
A direct assay method is described for l-pipecolate oxidase. The assay uses NaHSO3 to trap the δ-semialdehyde (AAS) formed as a direct reaction product of l-pipecolate oxidase from l-[3H]pipecolic acid. The adduct so formed was separated from the substrate on Dowex 50 (H+) column. The product was identified as [3H]AAS by amino acid analysis after breaking down the adduct by boiling under acidic conditions. The assay is simpler and more specific than fluorometric methods; it is also more sensitive; requiring at most 16 μg of liver peroxisome-enriched protein per assay. We have used this assay procedure to detect l-pipecolate oxidase in skin fibroblasts obtained from a control subject and from patients of hyperpipecolic acidaemia and Zellweger syndrome and found that this enzyme activity is present in the control, but absent or decreased in the patients with the peroxisomal disorders. 相似文献
12.
Conversion of aflatoxin B1 to its demethylated derivative, aflatoxin P1, has been achieved by treatment of the parent substance with lithium -butylmercaptide in hexamethyl phosphoramide for 2 hours at 75°C. A preliminary toxicologic evaluation in newborn mice showed aflatoxin P1 to cause some mortality at 150 mg/kg, whereas aflatoxin B1 had an LD5 0 of 9.5 mg/kg under comparable conditions. 相似文献
13.
Conditions for the production of a complementary DNA sequence for use in studies of ribosomal RNA are described. . DNA polymerase I is used to transcribe highly purified 28S ribosomal RNA from rat liver. The reaction is sensitive to the tertiary structure of the rRNA template-primer. The complementary DNA hybridizes to its rRNA template with a of 0.02. The hybrid formed between 28S ribosomal RNA and complementary DNA has a Tm of 73°C. The probe reacts with total rat nuclear RNA with a of 1.0. 相似文献
14.
Microsome-mediated metabolic activation of aflatoxin B1 (AFB1) and benzo[a]-pyrene (BP), as determined by the formation of DNA binding metabolites, was studied, using hepatic microsomes from untreated, phenobarbital (PB)-treated and 3-methylcholanthrene (MC)-treated male rats. Contrasting results were obtained for the two substrates: in the case of AFB1, microsomes from PB-treated rats were twice as active as microsomes from untreated and MC-treated rats, whereas, in the case of BP, microsomes from MC-treated rats were several fold more active than microsomes from untreated and PB-treated rats. These data strongly suggests enzyme multiplicity of microsomal mixed function oxygenase for the activation of carcinogens, especially AFB1 and BP whose reactive metabolites are believed to be epoxides. 相似文献
15.
Evidence for the formation of a gamma-phosphorylated glutamyl residue in the Escherichia coli acetate kinase reaction 总被引:5,自引:0,他引:5
Studies of phosphorylated acetate kinase, which has been reduced with [3H]sodium borohydride and subjected to acid hydrolysis, suggest that [3H] α-amino-δ-hydroxyvaleric acid is formed with a 20–25% overall yield. This finding is compatible with the formation of a γ-phosphorylated glutamyl residue upon incubation of enzyme with acetyl-P. 相似文献
16.
Acetylcholine stimulates hydrolysis of 32 P-labeled phosphatidic acid in guinea pig synaptosomes 总被引:3,自引:0,他引:3
[3H]-inositol or [3H]-arachidonate was injected intracerebrally into guinea pigs. Labeled nerve endings were incubated with Ach1 or CCh, both of which stimulate labeling of PhA and PhI from 32Pi by > 100% and 70% respectively. Their addition did not affect the labeled phosphatidyl-[3H]-inositol or [3H]-arachidonyl-diglyceride and -PhI. Enhanced hydrolysis of [3H]-inositol-PhiP and -PhIP2 in the presence of ACh, CCh or choline was not reversed by atropine. In a two-step experiment, PhA was labeled with 32Pi, and DNP was added to block further formation. Addition of ACh stimulated an atropine-sensitive in [32P]-PhA. 相似文献
17.
Hydrophobic anions of dipicrylamine and of sodium tetraphenylborate have been employed as probes of interfacial dipole potential variations in lipid bilayer membranes. Systematic variation of dipole potentials has been achieved by introduction of compounds incorporating N+ and B? charge centers. Distribution of hydrophilic and and hydrophobic groups relative to these charge centers has been shown to control the orientation in the membrane/solution interface of the electric dipole moment formed by these centers. Thus triphenyl-[4-trimethylphenylammonium] borate orients with the B? center, surrounded by phenyl groups, embedded in the membrane, while the smaller methylated N+ center is directed toward the aqueous phases. This orientation has been confirmed using dipicrylamine probe ions. Results obtained in this system have been interpreted quantitatively using a previously developed model incorporating discrete charge effects. A second class of compounds, borane (TnAB) complexes having the generic formula (CnH)3N+B?H3, have also been synthesized for this study, using even-carbon alkyls ranging from ethyl to decyl. Molecular orientation of the complex is with the N+ center and its associated alkyl groups directed into the membranes, while the protonated B? center is directed toward the aqueous phases, as confirmed by use of tetraphenylborate ions as probes. 相似文献
18.
Gennady A. Belitsky Elizabeth M. Khovanova Irene V. Budunova Helen G. Sharuptis 《Cell biology and toxicology》1985,1(3):133-143
Thegenotoxic activity of four mycotoxins has been studied. A high level of somatic mutagenesis in imaginal disks of Drosophila melanogaster larvae and DNA repair synthesis in human embryo and adult rat liver cell cultures was induced only by the strong carcinogen aflatoxin B1. Patulin somewhat elevated the level of somatic mutations in D. melanogaster, but did not elicit DNA repair synthesis. Citrinin and stachybotryotoxin were inactive in both systems.Abbreviations AFB1
aflatoxin B1
- DMSO
dimethylsulfoxide
-
3HTdR
tritiated thymidine
- SCE
sisterchromatid exchange
- UDS
unscheduled DNA synthesis 相似文献
19.
Eric R. Taylor 《Journal of biomolecular structure & dynamics》2013,31(3):533-550
Abstract An alternate model for surface noncovalent and surface covalent binding of aflatoxin B1 to N(7) of guanine in DNA is proposed. This model considers the out-of-plane motions of C(8) of aflatoxin B1 in those interactions. The covalent intercalated fit of aflatoxin B1 into DNA arises from steric adjustments made by DNA at the covalent intercalation site as well as local strain in the bond angles about N(7) of guanine and C(8) of aflatoxin B1. The bond angle about N(7) deviates modestly from the sp2 value toward the sp3 value. This study suggests that the surface covalent aflatoxin B1 -DNA complex serves only a minor role in aflatoxin's precarcinogenic interaction with DNA and is a likely correctable error. 相似文献
20.
In vivo biosynthesis of -linolenic acid in plants 总被引:6,自引:0,他引:6
C G Kannangara B S Jacobson P K Stumpf 《Biochemical and biophysical research communications》1973,52(2):648-655
[1-14C]acetate was readily incorporated into unsaturated fatty acids by leaf slices of spinach, barley and whole cells of and . In these systems the [14C] label in newly synthesized oleate and linoleate was approximately equally distributed in the C1–9 and the C10–18 fragments obtained by reductive ozonolysis of these acids, whereas in a-linolenic acid over 90% of the total [14C] was localized in the C1–9 fragment. While [1-14C]oleic acid was converted by whole cells of to [1-14C]linoleic and [1-14C]linolenic acids, [U-14C]oleic acid yielded [U-14C]linoleic acid but a-linolenic acid was labeled only in the carboxyl terminal carbon atoms. When spinach leaf slices were supplied with carboxyl labeled octanoic, decanoic, dodecanoic, tetradecanoic and octadecanoic acids, only the first three acids were converted to a-linolenic acids while the last two acids were ineffective. Thus we suggest that (a) linoleic acid is not the precursor of a-linolenic acid and (b) 12:3(3, 6, 9) is the earliest permissible trienoic acid which is then elongated to a-linolenic acid. 相似文献