Effects of a complex mixture of therapeutic drugs at environmental levels on human embryonic cells

Francesco Pomati, Sara Castiglioni, Ettore Zuccato, Roberto Fanelli, Davide Vigetti, Carlo Rossetti, Davide Calamari

Research output: Contribution to journalArticle

328 Citations (Scopus)

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 languageEnglish
Pages (from-to)2442-2447
Number of pages6
JournalEnvironmental Science and Technology
Volume40
Issue number7
DOIs
Publication statusPublished - Apr 1 2006

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Complex Mixtures
drug
Cells
Drug products
Cell proliferation
Pharmaceutical Preparations
Genes
Physiology
Cell death
Bezafibrate
Lincomycin
Sulfamethoxazole
Ranitidine
Hydrochlorothiazide
Ofloxacin
Atenolol
Proteins
Albuterol
gene
Ibuprofen

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 journalArticle

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