The in vitro PIG-A gene mutation assay: glycosylphosphatidylinositol (GPI)-related genotype-to-phenotype relationship in TK6 cells

@article{Krger2016TheIV,
  title={The in vitro PIG-A gene mutation assay: glycosylphosphatidylinositol (GPI)-related genotype-to-phenotype relationship in TK6 cells},
  author={Christopher T. Kr{\"u}ger and Bettina Fischer and Olivier Armant and Volker Morath and Uwe Str{\"a}hle and Andrea Hartwig},
  journal={Archives of Toxicology},
  year={2016},
  volume={90},
  pages={1729-1736}
}
In our previous work, we established an in vitro variant of the currently developed in vivo PIG-A assay as promising mutagenicity test system. We applied the human B-lymphoblastoid cell line TK6 for the in vitro assay development, which is based on the cellular glycosylphosphatidylinositol (GPI) status. At least 22 genes are involved in GPI biosynthesis, leading to the complex situation that, in principle, multiple genes could induce a GPI-deficient phenotype by acquiring inactivating mutations… 
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TLDR
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TLDR
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TLDR
The results confirm the existence of previously described mutations in the Tk1 and Trp53 genes and catalog millions of other mutations, many of which impair the function of genes with key roles in cell physiology and genetic toxicology.
A statistical approach for analyzing data from the in vivo Pig-a gene mutation assay.
TLDR
A statistical strategy based on a two factor model involving 'treatment' and 'time' incl.
Analysis of mutation in the rat Pig‐a assay: I) studies with bone marrow erythroid cells
TLDR
It is suggested that CD59‐deficient erythrocytes measured in the flow cytometry‐based pig‐a assay develop from BMEs containing mutations in the Pig‐a gene, which are precursors of peripheral red blood cells.
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TLDR
In this study, a corresponding in vitro variant of the PIG-A assay is established applying B-lymphoblastoid TK6 cells to demonstrate the mutagenicity of ethyl methanesulfonate, 4-nitroquinoline 1-oxide and UV-C irradiation in a dose-dependent and statistically significant manner.
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