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1.
2.
Cadmium (Cd) is a non-essential, highly toxic heavy metal and a ubiquitous environmental contaminant. Evidence exists that Cd can affect parameters which are of great importance in the response towards xenobiotics. However, there is a lack of information about the mechanisms that take place at the cellular and molecular levels upon dual exposure to Cd and other toxins. The purpose of the present work was therefore to examine the biochemical interactions between Cd and a well-known genotoxic hepatocarcinogen, 2-acetylaminofluorene (AAF) in isolated rat hepatocytes. The cells were incubated for 10 hr with a sub-cytotoxic concentration (0.22 M) of 109Cd. This was followed by a 10 hr exposure to 1 M [3H]AAF. Cellular distribution of Cd and 3H was determined. Sephadex G-75 elution profiles of the cytosol showed that Cd was almost entirely associated with the intermediate molecular weight (IMW) fractions containing metallothionein (MT) (>80%), and with high molecular weight proteins. In parallel, the highest proportion of 3H was found in the low molecular weight components. Further analysis of IMW fractions by DEAE A-25 anion-exchange chromatography revealed that, in addition to Cd, there was some 3H which coeluted along with MT-I and MT-II isoforms, but preferentially with MT-I. Moreover, Cd pretreatment caused a 1.6-fold increase in MT level, as measured by the silver-saturation assay. Under these conditions, there was a 17% lower binding of 3H to the DNA. This reduced binding was neither accompanied by diminished AAF uptake nor by inhibition of cytochrome P-450 activity. Taken together, these results suggest that Cd exposure has a protective effect against the genotoxicity of AAF. MT, whose synthesis is induced, could play a role in the Cd-AAF interaction through scavenging of reactive metabolites.Abbreviations AAF
2-acetylaminofluorene
- Cd
cadmium
- DMSO
dimethyl sulfoxide
- HBSS
Hank's balanced salt solution
- LDH
lactate dehydrogenase
- MT
metallothionein
- UDS
unscheduled DNA synthesis 相似文献
3.
Francine Denizeau Michel Marion Gaston Chevalier Michel G. Cote 《Cell biology and toxicology》1985,1(2):23-32
The biological activity of natural and synthetic mineral fibers has been examined. Natural attapulgite [(Mg, Al)2Si4O10(OH).4H20], synthetic xonotlite [Ca3Si3O8(OH)2] and natural sepiolite [Mg2Si3O8.2H2O] were selected. Genotoxic effects were investigated by means of a well established cellular model based upon the measurement of unscheduled DNA synthesis (UDS) in rat hepatocytes in primary culture. The intrinsic capacity of the fibers (1 and 10 µ/ml) to induce UDS was first tested. None of the fiber types showed detectable UDS-eliciting activity. Also, the possible modulation of the cellular response to genotoxic agents by the materials was examined by exposing the cells to mixtures of 2-acetylaminofluorene (AAF) (0.05 and 0.25 µg/ml) and fibers (1 and 10 µg/ml). In these experiments, the UDS response was significantly diminished in the presence of xonotlite. This phenomenon may reflect changes in the uptake and/or metabolism of AAF or may result from an inhibition of DNA repair processes, the latter suggesting a possible cocarcinogenic potential for this synthetic silicate. These results point to the immediate necessity of studying more extensively the biological effects of fibrous materials that can be used as substitutes for asbestos.Abbreviations AAF
2-acetylaminofluorene
- DMSO
dimethyl-sulfoxide
- FBS
fetal bovine serum
- IRDA
Institut de Recherche et de Développement sur l'Amiante
- LDH
lactate dehydrogenase
- UDS
unscheduled
- DNA
synthesis
- WME
Williams' Medium E
This work was supported by the Institut de Recherche et de Développement sur l'Amiante (IRDA), Sherbrooke, Canada. 相似文献
4.
5.
Identification and expression of water stress- and abscisic acid-regulated genes in a drought-tolerant sunflower genotype 总被引:17,自引:0,他引:17
6.
Corné M. J. Pieterse Anne-Marie C. E. Derksen Jindra Folders Francine Govers 《Molecular & general genetics : MGG》1994,244(3):269-277
The ipiB and ipiO genes of the potato late blight fungus Phytophthora infestans (Mont.) de Bary were isolated from a genomic library in a screen for genes induced in planta. Expression of these genes was studied during pathogenesis on various host tissues and different host plants, some of which show specific resistance against P. infestans infection. During pathogenesis on leaves and tubers of the fully susceptible potato cultivar (cv.) Ajax and on leaves of the fully susceptible tomato cv. Moneymaker, the P. infestans ipiB and ipiO genes show a transient expression pattern with highest mRNA levels in the early stages of infection. During the interaction with leaves of the partially resistant potato cv. Pimpernel, the expression is also transient but accumulation and disappearance of the mRNAs is delayed. Also in P. infestans inoculated onto a race-specific resistant potato cultivar and onto the nonhost Solanum nigrum, ipiB and ipiO mRNA is detectable during the initial stages of infection. Apparently, the expression of the ipiB and the ipiO genes is activated in compatible, incompatible and nonhost interactions. In encysted zoospores, ipiB and ipiO mRNA accumulation was not detectable, but during cyst germination and appressorium formation on an artificial surface the genes are highly expressed. Expression studies in mycelium grown in vitro revealed that during nutrient starvation the expression of the ipiB and ipiO genes is induced. For ipiO gene expression, carbon deprivation appeared to be sufficient. The ipiO gene promoters contain a sequence motif that functions as a glucose repression element in yeast and this motif might be involved in the regulation of ipiO gene expression. 相似文献
7.
8.
J Rocourt P Boerlin F Grimont C Jacquet J C Piffaretti 《International journal of systematic bacteriology》1992,42(1):171-174
The genomic relatedness between Listeria grayi and Listeria murrayi was reevaluated by using DNA-DNA hybridization, multilocus enzyme electrophoresis, and rRNA restriction fragment length polymorphism techniques. The high levels of similarity observed between the strains of these two species confirmed the data published since 1973 and indicated that they should be considered members of a single species. On grounds of priority, the species should be named L. grayi. 相似文献
9.
Andrea Villarino Marie-No?lle Rager Patrick A D Grimont Odile M M Bouvet 《European journal of biochemistry》2003,270(12):2689-2695
Cells that have lost the ability to grow in culture could be defined operationally as either alive or dead depending on the method used to determine cell viability. As a consequence, the interpretation of the state of 'nonculturable' cells is often ambiguous. Escherichia coli K12 cells inactivated by UV-irradiation with a low (UV1) and a high (UV2) dose were used as a model of nonculturable cells. Cells inactivated by the UV1 dose lost 'culturability' but they were not lysed and maintained the capacity to respond to nutrient addition by protein synthesis and cell wall synthesis. The cells also retained both a high level of glucose transport and the capacity for metabolizing glucose. Moreover, during glucose incorporation, UV1-treated cells showed the capacity to respond to aeration conditions modifying their metabolic flux through the Embden-Meyerhof and pentose-phosphate pathways. However, nonculturable cells obtained by irradiation with the high UV2 dose showed several levels of metabolic imbalance and retained only residual metabolic activities. Nonculturable cells obtained by irradiation with UV1 and UV2 doses were diagnosed as active and inactive (dying) cells, respectively. 相似文献
10.
B. Gallois Béatrice Langlois d'Estaintot Marie-Anges Michaux Alain Dautant Thierry Granier Gilles Précigoux José-Antonio Soruco Francine Roland Octavío Chavas-Alba Adelina Herbas Robert R. Crichton 《Journal of biological inorganic chemistry》1997,2(3):360-367
The X-ray structure of recombinant horse L-chain (rL) apoferritin, solved at 2.0?Å resolution with a final R factor of 17.9%, gives evidence that the residue at position 93 in the sequence is a proline and not a leucine, as found in earlier sequencing studies. The structure is isomorphous with other apoferritin structures, and we thus draw particular attention to those structural features which can be related to the stability and function of the protein. Analysis of hydrogen bonding and salt bridge interactions shows that dimers and tetramers are the most stable molecular entities within the protein shell: a result confirming earlier biophysical experiments. The stability of horse rL apoferritin to both dissociation into subunits at acidic pH values and to complete unfolding in guanidine chloride solutions is compared with that of other apoferritins. This emphasizes the role played by the salt bridge in the stability of this protein family. The horse rL apoferritin is significantly more resistant to denaturation than horse spleen ferritin, which in turn is more resistant than any human rH apoferritins, even those for which a salt bridge is restored. Finally, this structure determination not only establishes that a preformed pocket exists in L-chain apoferritin, at a site known to be able to bind porphyrin, but also underlines the particular function of a cluster of glutamic acids (E53, E56, E57 and E60) located at the entrance of this porphyrin-binding pocket. 相似文献