Comparison of chlorambucil and streptonigrin (NSC-45383) in the treatment of malignant lymphomas.
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Instant coffee exhibits genotoxic activity upon nitrosation at acidic pH values in the Ames tester strain TA100. Using adsorption chromatography (Amberlit XAD-2) it was observed that the major fraction of molecules responsible for the genotoxic activity upon nitrosation was not retained on this resin, suggesting that the polar molecules present in instant coffee could be responsible for the genotoxicity observed upon nitrosation. Some phenolic molecules present in instant coffee (catechol, caffeic acid, and chlorogenic acid) were also genotoxic upon nitrosation under the same experimental conditions. The concentrations of nitrosatable phenolic compounds in the studied coffee were determined by HPLC and their contributions to the total genotoxicity observed were studied. The results obtained suggest that besides phenolic compounds other molecules were also involved in the genotoxicity of this beverage upon nitrosation. Teratogenesis Carcinog. Mutagen. 20:241-249, 2000.
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Four new compounds, 3-(4-hydroxy-3,5-dimethoxyphenyl)propyl formate (1), 2,6-dimethoxy-4-[(1S)-3-methoxypropyl]phenol (2), (1R,2R)-4-[(3R)-3-hydroxybutyl]-3,3,5-trimethylcyclohex-4-ene-1,2-diol (3), and (1S,3R,3aR,6S,7S,9aR)-decahydro-1-(hydroxymethyl)-1,7-dimethyl-3a,7-methano-3aH-cyclopentacyclooctene (4) were isolated from the leaves of Acer truncatum, together with twelve known compounds. Their structures were elucidated on the basis of extensive spectroscopic techniques. The absolute configuration of compound 3 was established by the modified Mosher's method. All compounds were evaluated for antibacterial activities.
A method is reported for studying the effects of several factors at room temperature on the oxygen permeability of soft gelatin capsule shell films. The method involves the use of a permeability cell assembly and the spectrophotometric determïnation of oxygen with an alkaline pyrogallic acid solution. Factors investigated were relative humidity, plasticizers, equilibrium water, an insoluble additive, and film thickness. Results from the effects of film thickness and oxygen partial pressure correlated well with the permeability equation. For greatest stability of encapsulated oxygen-labile materials, it is recommended that the soft gelatin capsule shells be prepared with a low plasticizer concentration and that the finished capsules be stored at low relative humidity.
Myristicin, or methoxysafrole, is the principal aromatic constituent of the volatile oil of nutmeg, the dried ripe seed of Myristica fragrans. Myristicin is also found in several members of the carrot family (Umbelliferae). Several intoxications have been reported after an ingestion of approximately 5 g of nutmeg, corresponding to 1-2 mg myristicin/kg body weight (b.w.). Although these intoxications may be ascribed to the actions of myristicin, it is likely that other components of nutmeg may also be involved. The metabolism of myristicin resembles that of safrole. No information is available, however, concerning the quantitative importance of the different metabolic pathways. The acute toxicity of myristicin appears to be low. No toxic effects were observed in rats administered myristicin perorally at a dose of 10 mg/kg b.w., while 6-7 mg/kg b.w. may be enough to cause psychopharmacological effects in man. A weak DNA-binding capacity has been demonstrated, but there are no indications that myristicin exerts carcinogenic activity in short-term assays using mice. Intake estimations indicate that nonalcoholic drinks may be the most important single source of myristicin intake. Based on available data, it seems unlikely that the intake of myristicin from essential oils and spices in food, estimated to a few mg per person and day in this report, would cause adverse effects in humans. It is, however, at present not possible to make a complete risk assessment, as studies regarding genotoxicity and chronic toxicity, including reproductive toxicity and carcinogenicity, are still lacking.
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The white-rot fungus Phellinus ribis produced a single form of laccase, which was purified to apparent electrophoretic homogeneity from cultures induced with 2,5-xylidine. This protein was a dimer, consisting of two subunits of 76 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Carbohydrate analysis revealed that the enzyme contained about 28% carbohydrate content. The laccase appeared to be different from other known laccases by the UV-visible absorption spectrum analysis. One enzyme molecule contained one copper, one manganese, and two zinc atoms. The laccase showed optimal activity at pH 4.0-6.0, 5.0, and 6.0 with 2,6-dimethoxyphenol, ABTS [2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)], and syringaldazine, respectively. The enzyme preferably oxidized dimethoxyphenol and aromatic amine compounds. The stability of the laccase was low at acidic pH, whereas it showed high stability at neutral pH and mild temperature. The N-terminal amino acid sequence revealed a very low homology with other microbial laccases. With some substrates, the addition of manganese and H2O2 resulted in a remarkable increase in the oxidation rate. Without an appropriate phenolic substrate, the enzyme could not oxidize Mn(II) in the presence of H2O2 or pyrophosphate.
Mice given one of several widely consumed cola drinks in place of drinking water for up to 8 weeks developed significant levels of covalent liver DNA adducts in a time dependent manner, as measured by 32P-postlabeling. These adducts were not detected in mice given tap water or one of 3 non-cola beverages. Adducts chromatographically identical to those induced by cola drinks were detected in mice treated with extracts of nutmeg or mace, spices from the nutmeg tree (Myristica fragrans Houttuyn), or with myristicin (1-allyl-5-methoxy-3,4-methylenedioxybenzene), the major spice constituent of nutmeg. In addition, small amounts of adducts derived from the hepatocarcinogen safrole (1-allyl-3,4-methylenedioxybenzene), a minor constituent of nutmeg, were observed. Liver DNA adducts were also detected in fetal liver when pregnant mice were intubated with myristicin. Possible implications of these findings for human health are discussed.
The effect of myristicin on the expression of liver cytochrome P450s and its mRNA levels was examined in rats. Treatment of rats with myristicin (i.p., 500 mumol/kg) caused 2-20 fold increases in liver P450 1A1/2, 2B1/2, and 2E1 enzyme activities relative to controls. Immunoblot analysis using anti-rat liver P450 1A, 2B, and 2E1 showed that the increases in each of P450 protein levels by myristicin were consistent with those in enzyme activity levels. When increased levels of P450 mRNA by myristicin were examined by Northern blot analysis, levels of mRNA of P450 1A1/2 and 2B1/2 also increased. However, the level of P4502E1 mRNA did not increase. The total amount of spectrally detectable P450, also increased about 1.5-fold following treatment of myristicin. These results demonstrate that myristicin is an inducer of rat liver P450 1A1/2, 2B1/2, and 2E1, and that the induction involves increases in mRNA levels except in the case of P4502E1.
Mouse hepatoma Hepa-1c1c7 (Hepa-1) cells were treated with myristicin to assess the role of myristicin in the process of Cyp1a-1 induction. Treatment of Hepa-1 cells with myristicin increased Cyp1a-1 transcription in a dose-dependent manner as shown by analysis of 7-ethoxyresorufin O-deethylase activity, Cyp1a-1 protein level, and Cyp1a-1 mRNA. Myristicin, however, did not competitively displace [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin from the Hepa-1 cytosolic aryl hydrocarbon (Ah) receptor in a competitive Ah receptor binding analysis using sucrose density gradient sedimentation and did not affect formation of DNA-protein complexes between the Ah receptor and its DRE target in a gel mobility shift assay using oligonucleotides corresponding to DRE 3 of the Cyp1a-1. These results suggest that the induction of Cyp1a-1 gene expression by myristicin in Hepa-1 cells might occur through an Ah receptor-independent pathway.
The present studies were undertaken to elucidate the mechanism of induction of glutathione S-transferase (GST) in mouse liver by myristicin, an active constituent of parsley leaf. A/J albino mice, given 5 to 50 mg doses of myristicin, showed 4- to 14-fold increase in liver GST specific activity over the control. GST purified from equal amounts of control and myristicin-treated livers indicated a marked increase in the GST activity. A relatively higher increase in GST activity towards 2,4-dichloronitrobenzene and a profound increase in the levels of GST mu on Western blot analysis of the myristicin-treated mouse liver suggest a preferential induction of GST mu. Results of the study also indicate that out of the two mu class GST subunits (Mr. 26,500 and Mr. 25,000) expressed in liver only one (Mr. 26,500) is significantly elevated. Myristicin treatment caused a slight change in the GST pi levels while the levels of GST alpha showed a modest increase. These results suggest that myristicin could be an effective chemopreventive agent, particularly for carcinogens that are detoxified by the mu class GST.
L-arginine supplementation is hypothesized to reduce endothelial dysfunction and atherogenesis via increased biosynthesis of nitric oxide. Here we describe superoxide scavenging properties of arginine as an additional aspect which needs to be considered. Furthermore, arginine reduced copper-induced lipid peroxidation, indicating that superoxide anions essentially contribute to this process. In intact endothelial cells, L-arginine but not D-arginine diminished superoxide release and reduced cell-mediated breakdown of nitric oxide. Our data indicate that the reported vascular effects of L-arginine supplementation might involve an increased bioavailability of nitric oxide due to its superoxide scavenging properties beside a potential increased NO biosynthesis.
The putative multi-copper oxidase CueO had previously been implicated in intrinsic copper resistance in Escherichia coli. In this report we showed that the presence of CueO in the periplasm protected alkaline phosphatase from copper-induced damage. CueO contained four copper atoms per molecule and displayed spectroscopic properties typical of blue copper oxidases. CueO catalyzed the oxidation of p-phenylenediamine (pPD), 2,6-dimethoxyphenol (DMP) and exhibited ferroxidase activity in vitro.
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