Please use this identifier to cite or link to this item: https://ktisis.cut.ac.cy/handle/10488/14905
Title: Assessing the potential of pharmaceuticals and their transformation products to cause mutagenic effects: Implications for gene expression profiling
Authors: Vasquez Christodoulou, Marlen 
Tarapoulouzi, Maria 
Lambrianides, Nancy 
Hapeshi, Evroula 
Felekkis, Kyriakos 
Saile, Maria 
Sticht, Carsten 
Gretz, Norbert 
Fatta-Kassinos, Despo 
Keywords: Gene expression;Mammalian toxicology;Mixture toxicity;Mutagenicity;Transformation product;Pharmaceutical
Category: Chemical Sciences
Field: Natural Sciences
Issue Date: Nov-2016
Source: Environmental Toxicology and Chemistry, 2016, vol. 35 , no.11, pp. 2753–2764
Journal: Environmental Toxicology and Chemistry 
Abstract: The selection and prioritization of pharmaceuticals and their transformation products for evaluating effects on the environment and human health is a challenging task. One common approach is based on compounds (e.g., mixture composition, concentrations), and another on biology (e.g., relevant endpoint, biological organizational level). Both of these approaches often resemble a Lernaean Hydra-they can create more questions than answers. The present study embraces this complexity, providing an integrated approach toward assessing the potential effects of transformation products of pharmaceuticals by means of mutagenicity, estrogenicity, and differences in the gene expression profiles. Mutagenicity using the tk kinase assay was applied to assess a list of 11 priority pharmaceuticals, namely, atenolol, azithromycin, carbamazepine, diclofenac, ibuprofen, erythromycin, metoprolol, ofloxacin, propranolol, sulfamethoxazole, and trimethoprim. The most mutagenic compounds were found to be β-blockers. In parallel, the photolabile pharmaceuticals were assessed for their mixture effects on mutagenicity (tk assay), estrogenicity (T47D- KBluc assay), and gene expression (microarrays). Interestingly, the mixtures were mutagenic at the µg/L level, indicating a synergistic effect. None of the photolysed mixtures were statistically significantly estrogenic. Gene expression profiling revealed effects related mainly to certain pathways, those of the p53 gene, mitogen-activated protein kinase, alanine, aspartate, and glutamate metabolism, and translation-related (spliceosome). Fourteen phototransformation products are proposed based on the m/z values found through ultra-performance liquid chromatography-tandem mass spectrometry analysis. The transformation routes of the photolysed mixtures indicate a strong similarity with those obtained for each pharmaceutical separately. This finding reinforces the view that transformation products are to be expected in naturally occurring mixtures.
ISSN: 1552-8618
DOI: 10.1002/etc.3444
Collaboration : University of Cyprus
The Cyprus Institute of Neurology and Genetics
University of Nicosia
Heidelberg University
Rights: © SETAC
Type: Article
Appears in Collections:Άρθρα/Articles

CORE Recommender
Show full item record

WEB OF SCIENCETM
Citations

1
checked on May 25, 2020

Page view(s)

28
Last Week
0
Last month
1
checked on May 23, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.