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Effects of a Complex Mixture of Therapeutic Drugs at Environmental Levels on Human Embryonic Cells

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Department of Biotechnology and Molecular Sciences, University of Insubria, Varese 21100, Italy; Department of Environmental Health Sciences, “Mario Negri” Institute for Pharmacological Research, Milan 20157, Italy; and Department of Biomedical, Experimental and Clinical Sciences, University of Insubria, Varese 21100, Italy
Cite this: Environ. Sci. Technol. 2006, 40, 7, 2442–2447
Publication Date (Web):March 1, 2006
https://doi.org/10.1021/es051715a
Copyright © 2006 American Chemical Society
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Abstract

The potential risk associated with the presence of low levels of pharmaceuticals in aquatic environments is currently under debate. In this study we investigated the effects of 13 drugs merged to mimic both the association and low concentration (ng/L) profiles detected in the environment. The mixture comprised atenolol, bezafibrate, carbamazepine, cyclophosphamide, ciprofloxacin, furosemide, hydrochlorothiazide, ibuprofen, lincomycin, ofloxacin, ranitidine, salbutamol, and sulfamethoxazole. At environmental exposure levels, the drug mix inhibited the growth of human embryonic cells HEK293, with the highest effect observed as a 30% decrease in cell proliferation compared to controls. Pharmaceuticals activated stress-response signaling protein kinases (ERK1/2), and induced overexpres sion of glutathione-S-transferase P1 gene. No evidence was found for apoptosis or necrosis in HEK293 cells, although morphological changes were observed. The drug mixture effectively stimulated the expression of cell-cycle progression-mediating genes p16 and p21, with a slight accumulation of cells in the G2/M phase of the cell-cycle. Our results suggest that a mixture of drugs at ng/L levels can inhibit cells proliferation by affecting their physiology and morphology. This also suggests that water-borne pharmaceuticals can be potential effectors on aquatic life.

*

 Corresponding author phone:  +612 9385 3659; fax:  +612 9385 1591; e-mail:  [email protected]

∮

 Current address:  School of Biotechnology and Biomolecular Sciences, The University of New South Wales, 2052 Sydney, Australia.

†

 Department of Biotechnology and Molecular Sciences, University of Insubria.

§

 “Mario Negri” Institute for Pharmacological Research.

#

 Department Biomedical, Experimental and Clinical Sciences, University of Insubria.

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The influence of the SAPK/MAP kinase inhibitor SB203580 on cells growth and SAP/MAP activation. This material is available free of charge via the Internet at http://pubs.acs.org.

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