John Wiley & Sons, Ltd.

Assessing the mutagenic effect potential of pharmaceuticals and of their transformation products. Implications in the gene expression profiling

0
The selection and prioritization of pharmaceuticals and of their transformation products for evaluating effects on the environment and human health is a challenging task. Both compound‐ (e.g. mixture composition, concentrations) and biological‐ (e.g. relevant endpoint, biological organizational level) oriented approaches applied for tackling these issues often resemble a Lernaean hydra by creating more questions than answers. The present study embraces this complexity, providing an integrated approach to assess 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 eleven priority pharmaceuticals namely atenolol, azithromycin, carbamazepine, diclofenac, ibuprofen, erythromycin, metoprolol, ofloxacin, propranolol, sulfamethoxazole and trimethoprim. This screening identified β‐blockers as being the most mutagenic compounds. 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 in the mixture. None of the photolysed mixtures were statistically significant estrogenic. The gene expression profiling unveiled effects related mainly to the p53 gene, the mitogen‐activated protein kinase, the alanine, aspartate and glutamate metabolism and translation‐related (spliceosome) pathways. Fourteen photo‐transformation products are proposed based on the m/z values resulting after a UPLC/MS/MS analysis. The transformation routes of the photolysed mixtures indicate a strong similarity with the ones obtained for each pharmaceutical separately. This reinforces the view that transformation products are to be expected in naturally occurring mixtures. This article is protected by copyright. All rights reserved

Customer comments

No comments were found for Assessing the mutagenic effect potential of pharmaceuticals and of their transformation products. Implications in the gene expression profiling. Be the first to comment!