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- Jernbro, Susanne, et al.
(författare)
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Perfluorooctane Sulfonate Increases the Genotoxicity of Cyclophosphamide in the Micronucleus Assay with V79 Cells : Further Proof of Alterations in Cell Membrane Properties Caused by PFOS
- 2007
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Ingår i: Environmental Science and Pollution Research. - : Ecomed. - 0944-1344 .- 1614-7499. ; 14:2, s. 85-87
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Tidskriftsartikel (refereegranskat)abstract
- Perfluorooctane sulfonate (PFOS; C8F17SO3–) is a fully fluorinated organic compound which has been manufactured for decades and was used widely in industrial and commercial products. The recent toxicological knowledge of PFOS mainly concerns mono-substance exposures of PFOS to biological systems, leaving the potential interactive effects of PFOS with other compounds as an area where understanding is significantly lacking. However, a recent study, reported the potential of PFOS to enhance the toxicity of two compounds by increasing cell membrane permeability. This is of particular concern since PFOS has been reported to be widely distributed in the environment where contaminants are known to occur in complex mixtures. In this study, PFOS was evaluated alone and in combination with cyclophosphamide (CPP) to investigate whether a presence of PFOS leads to an increased genotoxic potential of CPP towards hamster lung V79 cells. Genotoxicity was investigated using the micronucleus(MN) assay according to the recent draft ISO/DIS 21427-2 method. PFOS alone demonstrated no genotoxicity up to a concentration of 12.5 μg/ml. However, PFOS combined with two different concentrations of CPP, with metabolic activation, caused a significant increase in the number of micronucleated cells compared to treatments with CPP alone. These results provide a first indication that PFOS has the potential to enhance the genotoxic action of CPP towards V79 cells, suggesting, together with the alterations in cell membrane properties shown previously, that genotoxicity of complex mixtures may be increased significantly by changes in chemical uptake. Together with an earlier study performed by the own working group, it can be concluded that PFOS alone is not genotoxic in this bioassay using V79 cells up to 12.5 μg/ml, but that further investigations are needed to assess the potential interaction between PFOS and other substances, in particular regarding the impact of membrane alterations on the uptake of toxic substances.
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| 3. |
- Keiter, Susanne, et al.
(författare)
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Does perfluorooctane sulfonate (PFOS) act as chemosensitizer in zebrafish embryos?
- 2016
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 548-549, s. 317-324
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Tidskriftsartikel (refereegranskat)abstract
- Earlier studies have shown that perfluorooctane sulfonate (PFOS) increases the toxicity of other chemicals by enhancing their uptake by cells and tissues. The present study aimed at testing whether the underlying mechanism of enhanced uptake of chemicals by zebrafish (Danio rerio) embryos in the presence of PFOS is by interference of this compound with the cellular efflux transporter Abcb4. Modifications of uptake/clearance and toxicity of two Abcb4 substrates, the fluorescent dye rhodamine B (RhB) and vinblastine, by PFOS were evaluated using 24 and 48. h post-fertilization (hpf) embryos. Upon 90. min exposure of 24. hpf embryos to 1. μM RhB and different PFOS concentrations (3-300. μM) accumulation of RhB in zebrafish was increased by up to 11.9-fold compared to controls, whereas RhB increases in verapamil treatments were 1.7-fold. Co-administration of PFOS and vinblastine in exposures from 0 to 48. hpf resulted in higher vinblastine-caused mortalities in zebrafish embryos indicating increased uptake of this compound. Interference of PFOS with zebrafish Abcb4 activity was further studied using recombinant protein obtained with the baculovirus expression system. PFOS lead to a concentration-dependent decrease of the verapamil-stimulated Abcb4 ATPase activity; at higher PFOS concentrations (250, 500. μM), also the basal ATPase activity was lowered indicating PFOS to be an Abcb4 inhibitor. In exposures of 48. hpf embryos to a very high RhB concentration (200. μM), accumulation of RhB in embryo tissue and adsorption to the chorion were increased in the presence of 50 or 100. μM PFOS. In conclusion, the results indicate that PFOS acts as inhibitor of zebrafish Abcb4; however, the exceptionally large PFOS-caused effect amplitude of RhB accumulation in the 1. μM RhB experiments and the clear PFOS effects in the experiments with 200. μM RhB suggest that an additional mechanism appears to be responsible for the potential of PFOS to enhance uptake of Abcb4 substrates.
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