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91.
Bermudo E Busquets R Barceló-Barrachina E Puignou L Santos FJ Galceran MT 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,802(1):61-68
The present paper describes the preparation of a suitable laboratory reference material (LRM) to validate analytical methods for the determination of heterocyclic amines (HAs) in foods. Three different lots of reference material were prepared using a beef extract which was contaminated with a well-known quantity of amines at different levels ranging from 10 to 75 ng/g. These materials were then lyophilised under determined conditions and, after grinding and sieving, homogenised and, finally, bottled and labelled. Homogeneity and stability studies were performed and no statistical differences were observed in the analysis of variances for within- and between-bottle results, thus demonstrating the homogeneity of the material. Stability at different storage temperatures (-18, +4, +25 and +40 degrees C) and times (1, 2, 3 and 6 months) was also tested. Therefore, the material can be considered homogeneous and stable and can be proposed for use in inter-comparison exercises for the determination of HAs. 相似文献
92.
Murkovic M 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,802(1):3-10
Heterocyclic aromatic amines (HAs) are mutagenic and carcinogenic substances that are formed in significant amounts during heating of meat or fish at temperatures of at least 150 degrees C. To investigate the chemistry lying behind the formation of these harmful substances model systems were established. The first aim was to identify the naturally occurring precursors, namely creatinine, amino acids and carbohydrates. Later these model systems were used to develop strategies for a reduction of the content of the heterocyclic aromatic amines and for the evaluation of the reaction mechanisms that lead to the formation of these substances. All these aspects are discussed in this review. 相似文献
93.
Vitaglione P Fogliano V 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,802(1):189-199
Heterocyclic amines (HAs) are mutagenic/carcinogenic compounds formed in meat during cooking. Several efforts have been made to minimize the risk associated to HA human exposure. Supplementation with antioxidants is considered a promising measure to reduce HA exposure because of their ability as inhibitors of HA formation or as blocking/suppressing agents on HA biotransformation/metabolism. The aim of this review is to present the current knowledge on the capability of synthetic and natural antioxidants to modulate HA-induced mutagenicity/carcinogenicity. Data show a general trend towards a reduction of HA formation both in model systems and in real foods as well as an effective modulation of biotransformation and metabolism. Phenolic compounds, particularly those from tea and olive oil, seem to be the most effective, although a great variability is observed because of the concentration-dependent pro- and antioxidant effects. 相似文献
94.
Boyce A Doehmer J Gooderham NJ 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,802(1):217-223
Resveratrol is a phytoalexin, that belongs to a family of naturally occurring stilbenes. It has been reported that resveratrol can inhibit chemical carcinogenesis in experimental animals and although the mechanisms involved are unknown, an anti-mutagen mechanism has been proposed. We have explored this hypothesis using mutagenicity assays based on bacterial (Salmonella typhimurium) and eukaryotic cells (Chinese hamster V79 cells). We found resveratrol to be potent in both systems, blocking the mutagenicity of the food-derived heterocyclic amines (HA) 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) at micromolar concentrations. Furthermore, in cells capable of activating 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine to cytotoxic derivatives, resveratrol was able to attenuate cytotoxicity. Paradoxically, in cells lacking the ability to activate PhIP, resveratrol itself was toxic and co-incubation with PhIP reduced this toxicity. Our data confirm the potent anti-mutagenic activity of resveratrol and support its potential as a chemopreventative. 相似文献
95.
Protein profiles of Mycobacterium vanbaalenii PYR-1 grown in the presence of high-molecular-weight polycyclic aromatic hydrocarbons (HMW PAHs) were examined by two-dimensional gel electrophoresis (2-DE). Cultures of M. vanbaalenii PYR-1 were incubated with pyrene, pyrene-4,5-quinone (PQ), phenanthrene, anthracene, and fluoranthene. Soluble cellular protein fractions were analyzed and compared, using immobilized pH gradient (IPG) strips. More than 1000 gel-separated proteins were detected using a 2-DE analysis program within the window of isoelectric point (pI) 4-7 and a molecular mass range of 10-100 kDa. We observed variations in the protein composition showing the upregulation of multiple proteins for the five PAH treatments compared with the uninduced control sample. By N-terminal sequencing or mass spectrometry, we further analyzed the proteins separated by 2-DE. Due to the lack of genome sequence information for this species, protein identification provided an analytical challenge. Several PAH-induced proteins were identified including a catalase-peroxidase, a putative monooxygenase, a dioxygenase small subunit, a small subunit of naphthalene-inducible dioxygenase, and aldehyde dehydrogenase. We also identified proteins related to carbohydrate metabolism (enolase, 6-phosphogluconate dehydrogenase, indole-3-glycerol phosphate synthase, and fumarase), DNA translation (probable elongation factor Tsf), heat shock proteins, and energy production (ATP synthase). Many proteins from M. vanbaalenii PYR-1 showed similarity with protein sequences from M. tuberculosis and M. leprae. Some proteins were detected uniquely upon exposure to a specific PAH whereas others were common to more than one PAH, which indicates that induction triggers not only specific responses but a common response in this strain. 相似文献
96.
Effectiveness of phytoremediation as a secondary treatment for polycyclic aromatic hydrocarbons (PAHs) in composted soil 总被引:5,自引:0,他引:5
A greenhouse study was conducted over a 12-month period to investigate the fate of polycyclic aromatic hydrocarbons (PAHs) in soil using phytoremediation as a secondary treatment. The soil was pretreated by composting for 12 weeks, then planted with tall fescue (Festuca arundinacea), annual ryegrass (Lolium multiflorum), and yellow sweet clover (Melilotus officinalis). Two sets of unvegetated controls also were evaluated, one fertilized and one unfertilized. Total PAH concentrations decreased in the tall fescue, annual ryegrass, and yellow sweet clover treatments by 23.9%, 15.3%, and 9.1%, respectively, whereas the control was reduced by less than 5%. The smaller two- and most of the three-ringed compounds--naphthalene, acenaphthylene, acenaphthene, fluorene, and anthracene--were not found in detectable concentrations in any of the treatments. The most probable number analysis for microbial PAH degraders did not show any statistically significant differences among treatments. There were significant differences among treatments (p < 0.05) for the residual concentrations of five of the target PAHs. Root surface area measurements indicated that tall fescue and annual ryegrass both had significantly higher root surface area than yellow sweet clover, although the two species were not significantly different from each other. The tall fescue treatment resulted in the highest root and shoot biomass, followed by annual ryegrass and yellow sweet clover, and also had the highest percent of contaminant removal after 12 months. These results imply a positive relationship between plant biomass development and PAH biodegradation. 相似文献
97.
由于在帕金森病中合成多巴胺所需的酪氨酸羟化酶(tyrosine hydroxylase,TH)和左旋芳香族氨基酸脱羧酶(aromatic L-amino acid decarboxylase,AADC)活性明显降低,所以补充多巴胺合成酶成为基因治疗帕金森病研究的主要手段。我们分别构建了重组逆转录病毒载体pLHCX/TH及pLNCX2/AADC,通过脂质体介导将带有目的基因的载体分别转到包装细胞PA317中,经筛选得到产病毒的细胞PA317/TH和PA317/AADC,采用免疫组化、原位杂交方法检测目的基因表达;细胞经裂解后进行的酶促反应产物多巴胺以高压液相电化学方法检测证明所克隆的T‘H及AADC基因具有功能活性;这两种基因工程改造细胞可以完成酶促动力学的功能,使L-dopa及多巴胺产生明显增加。本研究为用TH和AADC双基因对帕金森病进行基因治疗提供了一定的依据。 相似文献
98.
The constrained backbone torsion angle of a proline (Pro) residue has usually been invoked to explain its three-dimensional context in proteins. Here we show that specific interactions involving the pyrrolidine ring atoms also contribute to its location in a given secondary structure and its binding to another molecule. It is adept at participating in two rather non-conventional interactions, C-H...pi and C-H...O. The geometry of interaction between the pyrrolidine and aromatic rings, vis-à-vis the occurrence of the C-H...pi interactions has been elucidated. Some of the secondary structural elements stabilized by Pro-aromatic interactions are beta-turns, where a Pro can interact with an adjacent aromatic residue, and in antiparallel beta-sheet, where a Pro in an edge strand can interact with an aromatic residue in the adjacent strand at a non-hydrogen-bonded site. The C-H groups at the Calpha and Cdelta positions can form strong C-H...O interactions (as seen from the clustering of points) and such interactions involving a Pro residue at C' position relative to an alpha-helix can cap the hydrogen bond forming potentials of the free carbonyl groups at the helix C terminus. Functionally important Pro residues occurring at the binding site of a protein almost invariably engage aromatic residues (with one of them being held by C-H...pi interaction) from the partner molecule in the complex, and such aromatic residues are highly conserved during evolution. 相似文献
99.
Hydroxylation of benzylic methyl carbon atoms on drugs and carcinogenic polycyclic aromatic hydrocarbons (PAHs) forms benzylic alcohols. Many carcinogenic and mutagenic PAHs bear a primary or secondary benzylic hydroxyl group attached to the meso-region of the molecule. According to the unified theory, PAHs bearing a benzylic hydroxyl group are proximate carcinogenic metabolites. This paper demonstrates that carcinogenic benz[a]anthracenes bearing a formyl group at the meso-region undergo enzymatic reductive metabolism to the corresponding carcinogenic benzylic alcohol in vitro and in vivo. The unified theory would then predict sulfuric acid esterification of such benzylic alcohols as the final common step in their metabolic activation to generate ultimate electrophilic benzylic carbocations. Finally, oxidative metabolism of 7-formylbenz[a]anthracenes gives rise to corresponding carboxylic acids and other oxygenated metabolites that are carcinogenically inert. Thus, oxidative metabolism of meso-region formyl compounds represents an avenue for the elimination of the carcinogen in a detoxified form. 相似文献
100.
Chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile, TCIN, CAS 1897-45-6) is a broad range spectrum fungicide whose fungitoxic action has been associated with the rapid formation of conjugated chlorothalonil–cellular thiol derivatives, specifically with thiol-rich enzymes such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and with glutathione (GSH). The biotransformation reaction sequence between enzyme-activated glutathione (GSH) and chlorothalonil depletes cellular glutathione reserves. The conjugation of glutathione with chlorothalonil via nucleophilic aromatic substitution was modeled for an isolated reacting species using semiempirical self-consistent field molecular orbital (SCF-MO) theory at the PM3 level. The potential energy hypersurface at each of the three possible chlorinated attack sites on chlorothalonil was elaborated using a thiolate (CH3S–) anion as a model for an enzyme-activated glutathione molecule. Calculated free energies of activation for formation of mono-RSH conjugates suggest that the order of nucleophilic attack on chlorine positions in TCIN is 2>4, 6>5 although energy differences are small (on the order of 1–2 kcal mol–1). Meisenheimer or -complexes have been isolated as true intermediates on the hypersurface for each reaction, suggesting that the mechanism follows a two-step pathway.Electronic Supplementary Material available. 相似文献