Assessing the potential of pharmaceuticals and their transformation products to cause mutagenic effects: Implications for gene expression profiling
Ημερομηνία
2016Συγγραφέας
Vasquez, Marlen I.Tarapoulouzi, Maria
Lambrianides, Nancy
Hapeshi, E.
Felekkis, Kyriakos
Saile, Maria
Sticht, Carsten
Gretz, Norbert
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Source
Environmental Toxicology and ChemistryVolume
35Issue
11Pages
2753-2764Google Scholar check
Keyword(s):
Metadata
Εμφάνιση πλήρους εγγραφήςΕπιτομή
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 [beta]-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 µ g/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. Environ Toxicol Chem 2016 35:2753-2764. © 2016 SETAC