Article

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

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
Environ. Sci. Technol., 2006, 40 (7), pp 2442–2447
DOI: 10.1021/es051715a
Publication Date (Web): March 1, 2006
Copyright © 2006 American Chemical Society

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.

Citation data is made available by participants in Crossref's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search inSciFinder.

Explore by:

Metrics

Article Views: 2,202 Times
Received 29 August 2005
Date accepted 25 January 2006
Published online 1 March 2006
Published in print 1 April 2006
+
Altmetric Logo Icon More Article Metrics

This website uses cookies to improve your user experience. By continuing to use the site, you are accepting our use of cookies. Read the ACS privacy policy.

CONTINUE