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1.
Aflatoxin B1-2,3-oxide: evidence for its formation in rat liver in vivo and by human liver microsomes in vitro 总被引:12,自引:0,他引:12
D H Swenson E C Miller J A Miller 《Biochemical and biophysical research communications》1974,60(3):1036-1043
Injection of [3H]aflatoxin B1 into rats yielded covalently bound derivatives in hepatic DNA, rRNA, and protein. Mild acid hydrolysis of the DNA and rRNA adducts formed a derivative indistinguishable from 2,3-dihydro-2,3-dihydroxy-aflatoxin B1. The data indicate that approximately 60% of the nucleic acid adducts were derived from reactions with aflatoxin B1-2,3-oxide. Acid hydrolysis of rRNA-[3Haflatoxin B1 adduct formed by human liver microsomes also liberated the dihydrodiol in significant amount. The 2,3-oxide of aflatoxin B1 is a probable ultimate carcinogenic metabolite. 相似文献
2.
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
3.
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
4.
S Lemaire L Chouinard D Denis M Panico H R Morris 《Biochemical and biophysical research communications》1982,108(1):51-58
Deliberate miscompartmentalization of liver outer mitochondrial membrane (OMM) proteins and liver mitochondrial proteins has been achieved by polyethylene-glycol mediated OMM vesicle-hepatocyte or mitochondrial-hepatocyte fusion. Reductively methylated OMM and mitochondrial proteins (3H) are destroyed at rates remarkably similar to those for OMM (, 60–70 h) or mitochondrial proteins (, 84–104 h) in liver when studied over 4–5 days in hepatocyte monolayers cultured in conditions giving stabilized endogenous protein catabolic rates mimicking endogenous rates. Destruction of transplanted OMM proteins is partially sensitive to chloroquine, supporting some lysosomally mediated autophagic destruction of long-lived transplanted OMM proteins in hepatocyte monolayers. 相似文献
5.
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
6.
7.
At low concentrations (i.e., 10?12–10?9 mol/l), PGF1α and PGF2α very intensely stimulated both the DNA-synthetic and mitotic activities of hepatocytes in 4-day-old primary cultures of neonatral rat liver. DNA replication was more intensely enhanced by PGF2α than by PGF1α, whereas mitotic activity was nearly equally affected by the two prostaglandins. On the whole, the growth-promoting activity of PGF1α used by itself or in equimolar mixtures with other prostaglandins (. ., A1, E1, .) mimicked that of arachidonic acid we previously reported (1). On a molar basis, PGF2α by itself stimulated hepatocytes′ DNA synthesis is more powerfully than arachidonate did, and when used in equimolar mixtures with other prostaglandins was at least as potent as arachidonic acid. These observations establish prostaglandins of the F series as quite powerful commitment factors and, though by a lesser degree, also intracycle regulators for neonatal rat hepatocytes in primary culture. However, the understanding of the role(s) of prostaglandins of F and other series in the physiological control of hepatocytes′ proliferative activation must wait the clarification of their interaction(s) with other arachidonate derivative(s) and polypeptide growth factor(s) which also may be involved in the process. 相似文献
8.
The cellular distribution of 35S from 35S- thioacetamide was determined in rabbit liver subcellular fractions following its administration. Of the various fractions isolated, only the nucleolar fraction contained 35S counts that were insoluble in 10% trichloroacetic acid but soluble in trichloroacetic acid if the fraction was treated with trypsin but not RNase or DNase. These results demonstrate that a protein bound form of thioacetamide is present in the nucleolus following administration of this drug. 相似文献
9.
J Marie L Tichonicky J C Dreyfus A Kahn 《Biochemical and biophysical research communications》1979,87(3):862-868
Ribosomal proteins of were labelled with 32PO4. Three acid phosphoproteins were observed in the large subunit, while two basic ones were present in the small subunit. Ribosomal phosphoprotein S3 accounted for 70% of the total radioactivity and may be equivalent to S6 from rat liver. 相似文献
10.
G M Ledda A Columbano P M Rao S Rajalakshmi D S Sarma 《Biochemical and biophysical research communications》1980,95(2):816-821
In order to characterize rat liver DNA replicated on a carcinogen-damaged template, the replicated DNA was treated with S1-nuclease and the release of (14C)-dimethyl-nitrosamine induced 06-methylguanine, a lesion associated with miscoding and N-7-methylguanine, a lesion that does not miscode were monitored. The results indicated that both the methylated guanines became susceptible to S1-nuclease upon replication. However, a greater percentage of 06-methylguanine (22% of the total 06-methylguanine present in the DNA) compared to N-7-methylguanine (4% of the total N-7-methylguanine present in the DNA) was rendered acid soluble by S1-nuclease. The preferential release of 06-methylguanine compared to N-7-methylguanine from replicated DNA was interpreted to indicate its occurrence in local denatured regions probably generated as a result of misbase pairing. 相似文献
11.
The hypoglycemic agent, 2-tetradecylglycidic acid (TDGA), administered in vivo lowered the concentration of plasma glucose and ketone bodies but raised the concentration of liver and plasma triglycerides in 10-day-old suckling rats. Phospholipid and cholesterol content of the plasma and liver were unaffected by drug treatment. TDGA inhibited the in vivo oxidation of [1-14C]palmitate but not that of [1-14C]decanoate. In suckling rat liver perfusion, TDGA totally inhibited ketone body formation from palmitate and depressed ketone body production from decanoate by 20%. Liver ATP and ADP content in the presence of TDGA decreased although this was probably a reflection of the increased triglyceride content of the liver since the was the same as control livers. The results are discussed in relation to the diet and to the inhibition of carnitine acyl transferase in suckling rats. 相似文献
12.
C Hedgcoth K Thomas K Scheets S Allen 《Biochemical and biophysical research communications》1980,95(2):880-886
When murine sarcoma virus-transformed cells are labeled with [3H]lysine for various periods, 5 of 6 isoaccepting lysine tRNAs separable by RPC-5 chromatography are aminoacylated in 1 hr to the same extent that they are aminoacylated . The sixth isoacceptor, tRNA6Lys, is not aminoacylated to a measurable extent in 1 hr, although it is present in the tRNA prepared from the cells. All six isoacceptors are aminoacylated with [3H]lysine when the labeling period is 2 or 3 hr. These results further show that correlations of the amount of tRNA4Lys with cell division accurately reflect the situation . Results of differential centrifugation indicate that tRNA6Lys occurs in mitochondria. 相似文献
13.
M J Duchesne A A Attallah J B Lee 《Biochemical and biophysical research communications》1975,64(1):196-203
PGA1 was incubated with rabbit renal cortical homogenates containing HSA (0–4.5%). The ability of this tissue to readily metabolize PGA1 progressively decreased with increasing HSA levels in the incubates The rate of disappearance of 3H-PGA1 was twice as rapid in rats treated with salicylic acid (S. A.) in comparison to control animals; since only 30% of the injected radioactivity was bound to the plasma of the S.A. treated rats, as compared to 90% bound to control plasma, an association may exist between the degree of binding of 3H-PGA1 and its rate of clearance. The studies indicate that PGA1 interaction with HSA decreases its metabolism , and slows down its clearance , implicating HSA as a possible factor in prostaglandins metabolism . 相似文献
14.
C.D. Eskelson M. Chvapil M. LaFranconi K. Brendel S. Solomon E. Barker J.J. Vostal 《Life sciences》1981,29(25):2659-2665
A hepatocyte lipogehic system which uses 14C-acetate as a lipogenic precursor was used. Phosphatidylethanolamine is biosynthesized the most in this newly established lipogenic system. Cholesterol, triacylglycerols, free fatty acids, lecithin and other phospholipids are also biosynthesized in the system.When a lung mince is added to hepatocytes biosynthesizing lipids from 14C-acetate, an increase in lecithin (PC) formation greater than that of lung mince alone and hepatocyte alone is detected.This study not only supports the concept that the lung has the capacity to stimulate the liver for lecithin synthesis but also indicates that lung minces have the ability to produce a prostaglandin (s) which is/are inhibitory to lipogenesis in hepatocytes. Lung minces from rats given indomethacin also stimulated lecithin formation in hepatocytes. 相似文献
15.
Seung-ki Lee Richard A. Jungmann 《Biochemical and biophysical research communications》1981,102(1):538-544
The phosphorylation of RNA polymerase II after isoproterenol stimulation of confluent rat C6 glioma cell cultures has been investigated. Glioma cells were incubated in the presence of Na2H32PO4 and stimulated for 1 hour with the β-adrenergic agonist isoproterenol. The phosphorylation pattern was analyzed after purification of RNA polymerase II by immunoprecipitation, SDS-polyacrylamide gel electrophoresis and autoradiography. Isoproterenol markedly increased [32P]phosphate incorporation into the 214,000 dalton RNA polymerase subunit. Analysis of the phosphate acceptor amino acid revealed the presence of only [32P]phosphoserine. The data demonstrates an isoproterenol-induced structural modification of RNA polymerase II. 相似文献
16.
Phosphorylation of high mobility group proteins 14 and 17 by nuclear protein kinase NII in rat O6 glioma cells 总被引:1,自引:0,他引:1
J J Harrison R A Jungmann 《Biochemical and biophysical research communications》1982,108(3):1204-1209
High mobility group (HMG) proteins 14 and 17 of rat C6 glioma cells are phosphorylated on both serine and threonine. In HMG 14 about 60% of the total [32P]phosphate was identified as phosphoserine and 40% as phosphothreonine. In HMG 17, there was 88% phosphoserine and 12% phosphothreonine. Glioma cell nuclear protein kinase NII phosphorylates HMG 14 and 17 on serine as well as threonine and the relative percentages of [32P]phosphoamino acid are similar to those seen . Nuclear protein kinase NI and the type I and II cAMP-dependent protein kinases exhibit only minor phosphorylating activity towards HMG 14 and 17. We conclude that nuclear protein kinase NII is responsible for the phosphorylation of HMG 14 and 17 . 相似文献
17.
J R Benemann K Miyamoto P C Hallenbeck M A Murry 《Biochemical and biophysical research communications》1982,106(4):1196-1202
Hydrogenase activity in the thermophilic cyanobacterium, was studied both and hydrogen consumption required oxygen but not light, was about ten-fold higher than in mesophilic cyanobacteria, and was relatively insensitive to carbon monoxide. H2-supported acetylene reduction in reductant-limited cultures was a light-dependent, but O2-independent reaction. hydrogen evolution was unaffected by carbon monoxide, and this activity could be partially purified using a procedure developed for . 相似文献
18.
In previous reports from various laboratories, the levels of the microsomal cytochromes b5 and P-450 in hepatocytes in primary culture have been found to be very low and difficult to measure. The studies reported in this paper demonstrate that cytochromes b5 and P-450 in hepatocytes cultured on floating collagen membranes for periods of at least 10 days are maintained at levels readily measured by conventional techniques and comparable to those of liver . Addition of high levels of hydrocortisone (10?4M) to the culture medium for periods up to 10 days resulted in further increases in the levels of these cytochromes. Cells cultured in the presence of hydrocortisone exhibited the appearance of cytochrome P-448, in contrast to the cells cultured in the absence of hydrocortisone, where cytochrome P-450 was maintained. 相似文献
19.
David Scicchitano Anthony E. Pegg 《Biochemical and biophysical research communications》1982,109(3):995-1001
The demethylation of O6-methylguanine in double stranded DNA catalyzed by rat liver O6-methylguanine-DNA transmethylase was found to proceed much more rapidly when the DNA substrate was methylated to a high extent. When the content of O6-methylguanine in DNA was equal to 1 in 2000 guanines, the reaction was 90% complete within 2 min, but when the content was 1 in 500,000 it required 27 min at 37°C. These results suggest that the repair protein either moves along the DNA substrate or else has little selectivity for binding specifically to the sites containing O6-methylguanine rather than to the normal DNA. The repair of O6-methylguanine in rat liver occurred at rates comparable to those seen with the substrates alkylated to low extents and was virtually complete within 3 hours. These results provide strong evidence that this protein is the factor responsible for O6-methylguanine removal and explain the wide variation in time courses reported in the literature since substrates methylated to greatly different extents have been used for such experiments. 相似文献
20.
Gel filtration chromatography demonstrated the presence of two peaks of glutathione peroxidase activity assayed with cumene hydroperoxide in the soluble fraction of rat liver, brain, kidney, and testis. The peak with an approximate molecular weight of 45,000 (GSH-Px II) was purified from rat liver labeled with Na275SeO3. Chromatography on DEAE-cellulose, Sephadex G-150, DEAE-cellulose, and CM-cellulose resulted in the co-purification of glutathione-S-transferase activity measured with 1-chloro-2,4-dinitrobenzene and glutathione peroxidase activity assayed with cumene hydroperoxide, and in the removal of all detectable 75Se. Studies on GSH-Px II indicated that the apparent Km for both cumene and t-butyl hydroperoxides was considerably higher than that for purified seleno-glutathione peroxidase. The Vmax estimated with cumene hydroperoxide was only of that determined for the selenoenzyme at pH 7.5 and with 1 mM GSH. 相似文献