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

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 mixtur...

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Bibliographic Details
Published in:Environmental science & technology 2006-04, Vol.40 (7), p.2442-2447
Main Authors: Pomati, Francesco, Castiglioni, Sara, Zuccato, Ettore, Fanelli, Roberto, Vigetti, Davide, Rossetti, Carlo, Calamari, Davide
Format: Article
Language:English
Subjects:
Aquatic life
Biological and medical sciences
Cell Cycle
Cell Line
Embryo, Mammalian - cytology
Embryo, Mammalian - drug effects
Embryo, Mammalian - metabolism
Embryos
Environmental Pollutants - toxicity
Environmental pollutants toxicology
Environmental science
Gene Expression Regulation - drug effects
Humans
Inhibitor drugs
Kinases
Medical sciences
Pharmaceuticals
Toxicology
Water
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Summary: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.
ISSN:0013-936X
1520-5851
DOI:10.1021/es051715a