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

  • 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 IC50 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. IC50 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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Author:Pooja Gupta, Annika Gramatke, Ralf Einspanier, Christof Schütte, Max von Kleist, Jutta Sharbati
Document Type:Article
Parent Title (English):Toxicology in Vitro
First Page:179
Last Page:188
Tag: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
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