Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 434122
Title Transcriptomics analysis of primary mouse thymocytes exposed to bis(tri-n-butyltin)dioxide (TBTO)
Author(s) Kol, S.W.M.; Hendriksen, P.J.M.; Loveren, H. van; Peijnenburg, A.A.C.M.
Source Toxicology 296 (2012)1-3. - ISSN 0300-483X - p. 37 - 47.
DOI https://doi.org/10.1016/j.tox.2012.03.002
Department(s) RIKILT - BU Toxicology Bioassays & Novel Foods
RIKILT - Business Unit Safety & Health
Publication type Refereed Article in a scientific journal
Publication year 2012
Keyword(s) unfolded protein response - human cell-cycle - tri-n-butyltin - endoplasmic-reticulum - negative selection - rat thymocytes - in-vitro - thymus atrophy - cytochrome-c - kappa-b
Abstract The biocide bis(tri-n-butyltin)oxide (TBTO) causes thymus atrophy in rodents and is toxic to many cell types of which thymocytes are the most sensitive. To obtain insight in the mechanisms of action of TBTO, we exposed primary mouse thymocytes in vitro for 3, 6 and 11 h to 0.1, 0.5, 1 and 2 M TBTO. Subsequently, the cells were subjected to whole-genome gene expression profiling. Biological interpretation of the gene expression data revealed that TBTO affects a wide range of processes. Cell proliferation related genes were downregulated by all treatments except for 3 and 6 h 0.5 M TBTO which upregulated these genes. Treatment with TBTO resulted in upregulation of genes involved in endoplasmatic reticulum (ER) stress, NFkB and TNF pathways, and genes involved in DNA damage, p53 signaling and apoptosis. Remarkably, TBTO also increased the expression of genes that are known to be upregulated during T cell activation or during negative selection of thymocytes. The effect of TBTO on expression of genes involved in ER stress and apoptosis was confirmed by qPCR. Induction of the T cell activation response was corroborated by demonstrating that TBTO exposure resulted in translocation of NFAT to the nucleus, which is an essential event for T cell activation.
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