The Experts below are selected from a list of 3429 Experts worldwide ranked by ideXlab platform
Michael M Gottesman - One of the best experts on this subject based on the ideXlab platform.
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cross resistance to methotrexate and metals in human cisplatin resistant cell lines results from a pleiotropic defect in accumulation of these compounds associated with reduced plasma membrane binding proteins
1998Co-Authors: Dingwu Shen, Ira Pastan, Michael M GottesmanAbstract:Abstract Cross-resistance to a wide array of toxic chemicals is a common phenomenon in cisplatin-resistant cell lines. In this study, two independently isolated cisplatin-resistant cell lines derived from a human hepatoma and a cervical adenocarcinoma were shown to be cross-resistant to methotrexate (MTX) and several metal salts, such as Sodium Arsenite, Sodium arsenate, antimony potassium tartrate, and cadmium chloride. A pleiotropic defect resulting in reduced accumulation of cisplatin, 3[H]MTX, 73As3+, and 73As5+ was found in both cisplatin-resistant cell lines. Analysis by immunoblot, indirect immunofluorescence, and Northern hybridization showed dramatically reduced expression of the folate binding protein that mediates MTX uptake in both human cisplatin-resistant cell lines. By photoaffinity labeling with UV irradiation, specific binding proteins of Mr 230,000 and Mr 48,000 for 73As3+ and Mr 190,000 for 73As5+ were found in enriched plasma membrane of both human cisplatin-sensitive parental cell lines. Expression of these specific binding proteins was decreased in cells selected for cisplatin resistance. A protein band at Mr 36,000 that binds to 73As3+ was overexpressed in both human cisplatin-resistant cell lines. The finding of loss of distinct binding proteins for MTX, arsenate, and Arsenite in association with decreased accumulation of these agents in cisplatin-resistant cells suggests a pleiotropic, possibly regulatory, alteration in these cells.
Ricardo Marcos - One of the best experts on this subject based on the ideXlab platform.
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in vitro dna damage by arsenic compounds in a human lymphoblastoid cell line tk6 assessed by the alkaline comet assay
2004Co-Authors: Emma Guillamet, A Creus, Jessica Ponti, E Sabbioni, Salvador Fortaner, Ricardo MarcosAbstract:Arsenic is classified as a carcinogen for humans, but as a possible genotoxic agent. Thus, taking into account the controversial data about how arsenic compounds are able to induce genetic damage, we investigated the possible genotoxic activity of different arsenic compounds in the TK6 human lymphoblastoid cell line using the alkaline Comet assay. Eight different inorganic and organic arsenical compounds have been selected as follows: three inorganic (Sodium Arsenite, Sodium arsenate and Sodium hexafluorarsenate) and five organic (monomethylarsonic and dimethylarsinic acids, arsenobetaine, tetramethylarsonium iodide and tetraphenylarsonium chloride). According to their toxicity and genotoxicity, the highest concentration tested was 10 mM, and the duration of the treatments was 30 min or 3 h. The results indicate that some compounds belonging to both the organic and inorganic species were able to induce significant increases in the tail moment, the parameter used to determine genotoxicity. Thus, the inorganic compounds Sodium Arsenite and Sodium arsenate (but not Sodium hexafluoroarsenate) were genotoxic, while among the organoarsenic species tested only tetramethylarsonium iodide and tetraphenylarsonium chloride compounds (but not monomethylarsonic, dimethylarsinic acids and arsenobetaine) induced significant increases in the tail moment. Nevertheless, genotoxic induction was generally only observed at the highest doses tested.
Dingwu Shen - One of the best experts on this subject based on the ideXlab platform.
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cross resistance to methotrexate and metals in human cisplatin resistant cell lines results from a pleiotropic defect in accumulation of these compounds associated with reduced plasma membrane binding proteins
1998Co-Authors: Dingwu Shen, Ira Pastan, Michael M GottesmanAbstract:Abstract Cross-resistance to a wide array of toxic chemicals is a common phenomenon in cisplatin-resistant cell lines. In this study, two independently isolated cisplatin-resistant cell lines derived from a human hepatoma and a cervical adenocarcinoma were shown to be cross-resistant to methotrexate (MTX) and several metal salts, such as Sodium Arsenite, Sodium arsenate, antimony potassium tartrate, and cadmium chloride. A pleiotropic defect resulting in reduced accumulation of cisplatin, 3[H]MTX, 73As3+, and 73As5+ was found in both cisplatin-resistant cell lines. Analysis by immunoblot, indirect immunofluorescence, and Northern hybridization showed dramatically reduced expression of the folate binding protein that mediates MTX uptake in both human cisplatin-resistant cell lines. By photoaffinity labeling with UV irradiation, specific binding proteins of Mr 230,000 and Mr 48,000 for 73As3+ and Mr 190,000 for 73As5+ were found in enriched plasma membrane of both human cisplatin-sensitive parental cell lines. Expression of these specific binding proteins was decreased in cells selected for cisplatin resistance. A protein band at Mr 36,000 that binds to 73As3+ was overexpressed in both human cisplatin-resistant cell lines. The finding of loss of distinct binding proteins for MTX, arsenate, and Arsenite in association with decreased accumulation of these agents in cisplatin-resistant cells suggests a pleiotropic, possibly regulatory, alteration in these cells.
Emma Guillamet - One of the best experts on this subject based on the ideXlab platform.
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in vitro dna damage by arsenic compounds in a human lymphoblastoid cell line tk6 assessed by the alkaline comet assay
2004Co-Authors: Emma Guillamet, A Creus, Jessica Ponti, E Sabbioni, Salvador Fortaner, Ricardo MarcosAbstract:Arsenic is classified as a carcinogen for humans, but as a possible genotoxic agent. Thus, taking into account the controversial data about how arsenic compounds are able to induce genetic damage, we investigated the possible genotoxic activity of different arsenic compounds in the TK6 human lymphoblastoid cell line using the alkaline Comet assay. Eight different inorganic and organic arsenical compounds have been selected as follows: three inorganic (Sodium Arsenite, Sodium arsenate and Sodium hexafluorarsenate) and five organic (monomethylarsonic and dimethylarsinic acids, arsenobetaine, tetramethylarsonium iodide and tetraphenylarsonium chloride). According to their toxicity and genotoxicity, the highest concentration tested was 10 mM, and the duration of the treatments was 30 min or 3 h. The results indicate that some compounds belonging to both the organic and inorganic species were able to induce significant increases in the tail moment, the parameter used to determine genotoxicity. Thus, the inorganic compounds Sodium Arsenite and Sodium arsenate (but not Sodium hexafluoroarsenate) were genotoxic, while among the organoarsenic species tested only tetramethylarsonium iodide and tetraphenylarsonium chloride compounds (but not monomethylarsonic, dimethylarsinic acids and arsenobetaine) induced significant increases in the tail moment. Nevertheless, genotoxic induction was generally only observed at the highest doses tested.
Janice W. Yager - One of the best experts on this subject based on the ideXlab platform.
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Lung retention and bioavailability of arsenic after single intratracheal administration of Sodium Arsenite, Sodium arsenate, fly ash and copper smelter dust in the hamster
1995Co-Authors: Jean P. Buchet, Robert R. Lauwerys, Janice W. YagerAbstract:Arsenic is present in airborne particulate material released by coal-fired power plants and non-ferrous metal smelters. We have assessed whether the physico-chemical properties of arsenic in such particles play a role in its lung retention and uptake by the body. Female hamsters were given a single intratracheal instillation of fly ash or copper smelter dust suspensions (at doses of 50 or 100 μg As kg^−1) or identical amounts of soluble tri- and pentavalent arsenic, in the presence or absence of an inert dust material (tungsten carbide). The concentration of the element was measured in a 24 hour urine sample collected on the 1st, 2nd and 6th day after treatment and arsenic remaining in lung tissue was determined at the end of the same time periods. Both lung retention and urinary As excretion indicate a prolonged contact of the lung tissue with particulate As in contrast to soluble As salts. In addition to the effect of solubility described here, more research is needed to determine the effect of particle size and lung loading on retention, as well as the potential differences in the lung inflammatory response using arsenic-rich particulates from various sources.