1. A Database of IC50 Values and Principal Component Analysis of Results from Six Basal Cytotoxicity Assays, for Use in the Modelling of the In Vivo and In Vitro Data of the EU ACuteTox Project
- Author
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Sarah Watts, Michael Sjöström, Hans Raabe, Rodger Curren, Richard H. Clothier, Jessica Mainez, Paul J. Dierickx, Monika Owen, Thaly Lakhanisky, Vanessa Hernandez, Monica Betanzos, Roel Anthonissen, Nicola Bourne, and Myriam Fabre
- Subjects
Cell Survival ,Cycloheximide ,Biology ,Animal Testing Alternatives ,Toxicology ,computer.software_genre ,General Biochemistry, Genetics and Molecular Biology ,3T3 cells ,Cell Line ,Inhibitory Concentration 50 ,Mice ,chemistry.chemical_compound ,Basal (phylogenetics) ,Adenosine Triphosphate ,In vivo ,Toxicity Tests, Acute ,medicine ,Animals ,Humans ,Cytotoxicity ,Principal Component Analysis ,Database ,In vitro toxicology ,3T3 Cells ,General Medicine ,In vitro ,Medical Laboratory Technology ,medicine.anatomical_structure ,Databases as Topic ,chemistry ,Cell culture ,computer - Abstract
The main aim of the ACuteTox project (part of the EU 6th Framework programme) is to demonstrate that animal tests for acute systemic toxicity can be replaced by alternative in vitro assays. In this project, data for 97 reference chemicals were collected in the AcuBase database, designed to handle deposited in vitro and in vivo (human and animal) data. To demonstrate the applicability of in vitro basal cytotoxicity tests and in vitro– in vivo modelling, it was deemed necessary to obtain data that were generated via defined standard operating procedures. The molar basal cytotoxicity IC50 values (the 50% inhibitory concentrations for the endpoint measured) for a mouse fibroblast cell line (3T3), a human hepatic cell line (HepG2), a rat hepatic cell line (Fa32), and a human neutrophil cell line (HL-60), were compared, and gave an R2 correlation of 0.83. To identify chemicals that showed differential cytotoxicity to the various cell types involved, principal component analysis (PCA) was undertaken independently, once all the results had been returned. This showed that colchicine, cycloheximide, digoxin, 5-fluorouracil and hexachlorobenzene gave the lowest correlations with the first score vector of the PCA. The results presented are to be used to identify outliers that need to be further studied via the use of tissue-specific in vitro assays.
- Published
- 2008