In silicio cytotoxicity assessment on cultured rat intestinal cells deduced from cellular impedance measurements

Please always quote using this URN: urn:nbn:de:0297-zib-62666
  • Early and reliable identification of chemical toxicity is of utmost importance. At the same time, reduction of animal testing is paramount. Therefore, methods that improve the interpretability and usability of in vitro assays are essential. xCELLigence’s real-time cell analyzer (RTCA) provides a novel, fast and cost effective in vitro method to probe compound toxicity. We developed a simple mathematical framework for the qualitative and quantitative assessment of toxicity for RTCA measurements. Compound toxicity, in terms of its 50% inhibitory concentration IC_{50} on cell growth, and parameters related to cell turnover were estimated on cultured IEC-6 cells exposed to 10 chemicals at varying concentrations. Our method estimated IC50 values of 113.05, 7.16, 28.69 and 725.15 μM for the apparently toxic compounds 2-acetylamino-fluorene, aflatoxin B1, benzo-[a]-pyrene and chloramphenicol in the tested cell line, in agreement with literature knowledge. IC_{50} values of all apparent in vivo non-toxic compounds were estimated to be non-toxic by our method. Corresponding estimates from RTCA’s in-built model gave false positive (toxicity) predictions in 5/10 cases. Taken together, our proposed method reduces false positive predictions and reliably identifies chemical toxicity based on impedance measurements. The source code for the developed method including instructions is available at https://git.zib.de/bzfgupta/toxfit/tree/master.

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Metadaten
Author:Pooja Gupta, Annika Gramatke, Ralf Einspanier, Christof Schütte, Max von Kleist, Jutta Sharbati
Document Type:ZIB-Report
Tag:IC_{50}; Mathematical modeling; Real-time cell analyzer; Toxicity
MSC-Classification:92-XX BIOLOGY AND OTHER NATURAL SCIENCES / 92Cxx Physiological, cellular and medical topics / 92C37 Cell biology
92-XX BIOLOGY AND OTHER NATURAL SCIENCES / 92Cxx Physiological, cellular and medical topics / 92C42 Systems biology, networks
92-XX BIOLOGY AND OTHER NATURAL SCIENCES / 92Cxx Physiological, cellular and medical topics / 92C45 Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.) [See also 80A30]
Year of first publication:2017
Series (Serial Number):ZIB-Report (17-08)
ISSN:1438-0064
Published in:To appear in ...

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