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 overexpression 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.
| Original language | English |
|---|---|
| Pages (from-to) | 2442-2447 |
| Number of pages | 6 |
| Journal | Environmental Science and Technology |
| Volume | 40 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Apr 1 2006 |
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ASJC Scopus subject areas
- Environmental Science(all)
- Environmental Chemistry
- Environmental Engineering
Cite this
Effects of a complex mixture of therapeutic drugs at environmental levels on human embryonic cells. / Pomati, Francesco; Castiglioni, Sara; Zuccato, Ettore; Fanelli, Roberto; Vigetti, Davide; Rossetti, Carlo; Calamari, Davide.
In: Environmental Science and Technology, Vol. 40, No. 7, 01.04.2006, p. 2442-2447.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of a complex mixture of therapeutic drugs at environmental levels on human embryonic cells
AU - Pomati, Francesco
AU - Castiglioni, Sara
AU - Zuccato, Ettore
AU - Fanelli, Roberto
AU - Vigetti, Davide
AU - Rossetti, Carlo
AU - Calamari, Davide
PY - 2006/4/1
Y1 - 2006/4/1
N2 - 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 overexpression 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.
AB - 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 overexpression 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.
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U2 - 10.1021/es051715a
DO - 10.1021/es051715a
M3 - Article
C2 - 16646487
AN - SCOPUS:33645773451
VL - 40
SP - 2442
EP - 2447
JO - Environmental Science & Technology
JF - Environmental Science & Technology
SN - 0013-936X
IS - 7
ER -