CYTOTHREAT

Fate and effects of cytostatic pharmaceuticals in the environment and the identification of biomarkers for and improved risk assessment on environmental exposure

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'CytoThreat addresses the need to assess the risks of pharmaceuticals released in the environment, focusing on cytostatic drugs because they are highly hazardous compounds due to their genotoxic properties which may cause unexpected long term effects. Their release in the environment may lead to systemic ecological effects and increased cancer incidence, reduced fertility and malformations in the offspring in humans. The occurrence, distribution and fate of selected widely used cytostatics in different aquatic matrices, their acute and chronic toxicity and impact on the stability of the genetic material in a variety of aquatic organisms representing different trophic levels is addressed to provide data sets necessary for scientifically based risk assessment. Special emphasis is put on the combined effects of environmentally relevant mixtures. A combination of state-of-the art analytical chemistry, in vivo and in vitro systems, and ‘OMICS’ technologies is applied. In vivo studies with zebrafish models aim at identifying linkages between the genomic profiles, exposure conditions and adverse effects in vertebrates to identify molecular biomarkers for adverse effects of specific groups of cytostatics to be used as diagnostic markers and for predicting synergistic effects of combined exposures. Comparative in vitro genotoxicity and transcriptomic studies with zebrafish and human derived cells will provide additional information for the extrapolation of toxicological data to humans. Comparisons with the hazardous effects of other groups of pharmaceuticals will provide knowledge on the magnitude of the problem. CytoThreat will generate new knowledge on environmental and health risks of cytostatics and provide objective arguments for recommendations and regulations. Partners form 5 member states and 2 associated countries with complementary expertise in analytical chemistry, aquatic and genetic toxicology, and genomics and bioinformatics are involved.'

Introduzione (Teaser)

Drugs commonly used for chemotherapy are finding their way into water resources. Scientists are conducting comprehensive studies on the concentration, distribution and toxicity of these the residues of these compounds.

Descrizione progetto (Article)

Pharmaceuticals have had a major positive impact on public health. However, medicine should not be taken by a person who is not sick and the adage could not be truer in the case of cytostatic drugs used to treat cancer. These drugs stop the growth and division of cells and their release into the environment can cause ecological effects and resulting downstream effects on cancer incidence, fertility and genetic birth defects.

Scientists are studying cytostatic drugs in freshwater organisms and human cell lines with EU funding of the Cytothreat project. Researchers selected four cytostatic compounds (5-fluorouracyl, imatinib, etoposide and cisplatin) and mixtures of these based on the most commonly used cocktails of chemotherapy drugs and their consumption.

The team developed an automated detection methodology exploiting solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) and other techniques. This is capable of detecting the cytostatic pharmaceuticals, metabolites and transformation products in aqueous samples with appropriate selectivity, sensitivity and reliability. Investigators are using it to determine the occurrence, distribution and fate of cytostatics and their breakdown products.

Researchers have carried out acute eco-toxicological studies of the four cytostatics on aquatic organisms at various trophic levels, including algae, bacteria, crustaceans and zebrafish (representing the vertebrates). Important differences in sensitivity were observed both among the species and with respect to the cytostatic compounds.

Cytothreat is also evaluating differences in toxicity to the various compounds in human cells and zebrafish cells to provide a scientific basis for extrapolation of toxicological data to humans and identification of early biomarkers of long-term effects. Cytotoxicity studies evaluating DNA damage showed similar dose-response profiles to the four cytostatics in zebrafish and human cells. Scientists are now conducting related toxicogenomic studies in vitro and in vivo.

Cytothreat is filling an important gap in knowledge regarding the effects of cytostatic drugs on aquatic organisms and on human beings. In addition, determining the concentration and distribution of these hazardous compounds in water resources will have important impact on water quality management programmes. Taken together, Cytothreat is expected to play a major role in safeguarding the public from toxic pharmaceuticals and their by-products.