Title
Elucidating toxicological mechanisms of current flame retardants using a bacterial gene profiling assay Elucidating toxicological mechanisms of current flame retardants using a bacterial gene profiling assay
Author
Faculty/Department
Faculty of Sciences. Biology
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Oxford ,
Subject
Biology
Pharmacology. Therapy
Source (journal)
Toxicology in vitro. - Oxford
Volume/pages
29(2015) :8 , p. 2124-2132
ISSN
0887-2333
ISI
000364892000017
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Flame retardants are ubiquitously used chemicals that have been shown to contaminate environments. Toxicological data is largely limited, with little insight into their molecular modes of action that may give rise to their toxic phenotypes. Such insight would aid more effective risk assessments concerning these compounds, while also improving molecular design. We therefore used a bacterial stress-gene profiling assay to screen twelve currently-used flame retardants to obtain mechanistic insights of toxicity. Both brominated and organophosphate flame retardants were tested. All compounds showed statistically significant inductions of several stress genes when compared to control treatments. Triphenyl phosphate, tris(2-butoxyethyl) phosphate, tris(1,3-dichloro-2-propyl)phosphate, tris(butyl)phosphate, and tetrabromobisphenol A elicited (at least) two-fold inductions for any of the stress genes. When looking at absolute induction levels, the promoters induced are indicative of protein perturbation, DNA integrity and membrane integrity. However, normalising for the different induction potentials of the different stress genes and clustering using hierarchical and k-means algorithms indicated that in addition to protein and DNA damage, some compounds also resulted in growth arrest and oxidative damage. This research shows that this assay allows for the determination of toxicological modes-of-action while clustering and accounting for induction potentials of the different genes aids better risk assessment.
E-info
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