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@ARTICLE{Aschauer:126063,
author = {L. Aschauer and A. Limonciel and A. Wilmes and S.
Stanzel$^*$ and A. Kopp-Schneider$^*$ and P. Hewitt and A.
Lukas and M. O. Leonard and W. Pfaller and P. Jennings},
title = {{A}pplication of {RPTEC}/{TERT}1 cells for investigation of
repeat dose nephrotoxicity: {A} transcriptomic study.},
journal = {Toxicology in vitro},
volume = {30},
number = {1 Pt A},
issn = {0887-2333},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DKFZ-2017-02178},
pages = {106 - 116},
year = {2015},
abstract = {The kidney is a major target organ for toxicity. Incidence
of chronic kidney disease (CKD) is increasing at an alarming
rate due to factors such as increasing population age and
increased prevalence of heart disease and diabetes. There is
a major effort ongoing to develop superior predictive models
of renal injury and early renal biomarkers that can predict
onset of CKD. In the EU FP7 funded project, Predict-IV, we
investigated the human renal proximal tubule cells line,
RPTEC/TERT1 for their applicability to long term nephrotoxic
mechanistic studies. To this end, we used a tiered strategy
to optimise dosing regimes for 9 nephrotoxins. Our final
testing protocol utilised differentiated RPTEC/TERT1 cells
cultured on filter inserts treated with compounds at both
the apical and basolateral side, at concentrations not
exceeding IC10, for 14 days in a 24 h repeat application.
Transepithelial electrical resistance and supernatant
lactate were measured over the duration of the experiments
and genome wide transcriptomic profiles were assayed at day
1, 3 and 14. The effect of hypoxia was investigated for a
subset of compounds. The transcriptomic data were analysed
to investigate compound-specific effects, global responses
and mechanistically informative signatures. In addition,
several potential clinically useful renal injury biomarkers
were identified.},
keywords = {Lactates (NLM Chemicals) / Pharmaceutical Preparations (NLM
Chemicals)},
cin = {C060},
ddc = {610},
cid = {I:(DE-He78)C060-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25450743},
doi = {10.1016/j.tiv.2014.10.005},
url = {https://inrepo02.dkfz.de/record/126063},
}