Interindividual variation in response to xenobiotic exposure established in precision-cut human liver slices

Highlights • Interindividual variation in GE/EA mostly exceeds variation in phenotypical endpoints. • Baseline CYP levels correlate to several response parameters over individuals. • A role for CYP1B1 in metabolism of 2-nitrofluorene is suggested by network analysis. • Network modelling is able to d...

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Veröffentlicht in:	Toxicology (Amsterdam) 2014-09, Vol.323, p.61-69
Hauptverfasser:	Jetten, Marlon J.A, Claessen, Sandra M, Dejong, Cornelis H.C, Lahoz, Agustin, Castell, José V, van Delft, Joost H.M, Kleinjans, Jos C.S
Format:	Artikel
Sprache:	eng
Schlagworte:	Acetaminophen Acetaminophen - toxicity Aflatoxin B1 - toxicity Aflatoxins Bayesian network Benzo(a)pyrene - toxicity Carcinogens Cell Survival - drug effects Comet Assay Cytochrome P-450 Enzyme System - genetics DNA Damage Emergency Exposure Fluorenes - toxicity Gene Expression Glutathione Transferase - genetics Human Humans Interindividual variation L-Lactate Dehydrogenase - metabolism Liver Liver - drug effects Liver - metabolism Mathematical models Metabolism NAD(P)H Dehydrogenase (Quinone) - genetics Precision-cut liver slices Toxicity Xenobiotics - toxicity
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Beschreibung
Zusammenfassung:	Highlights • Interindividual variation in GE/EA mostly exceeds variation in phenotypical endpoints. • Baseline CYP levels correlate to several response parameters over individuals. • A role for CYP1B1 in metabolism of 2-nitrofluorene is suggested by network analysis. • Network modelling is able to define key parameters in a compound-specific response.
ISSN:	0300-483X 1879-3185
DOI:	10.1016/j.tox.2014.06.007