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 (3 pp) |
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Authors: | Harald Färber Paul Jones John Giesy Magnus Engwall |
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Institution: | Dept. of Zoology, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg, Germany. |
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Abstract: | Background, Aim and Scope
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 mg/L. 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 only. These results provide a first indication that PFOS has the potential
to enhance the genotoxic action of CPP towards V79 cells, suggesting that 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 mg/L, 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.
Materials and Methods:
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Results:
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Discussion:
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Conclusions:
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Recommendations and Perspectives:
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Keywords: | PFOS Perfluorooctane sulfonate micronucleus assay genotoxicity alterations in cell membrane properties |
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