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Ecotoxicoproteomics approach to assess the risk of anticancer drugs to aquatic fauna

Titel Englisch Ecotoxicoproteomics approach to assess the risk of anticancer drugs to aquatic fauna
Gesuchsteller/in Buclin Thierry
Nummer 132344
Förderungsinstrument Projekte
Forschungseinrichtung Unité de néphrologie pédiatrique CHUV
Hochschule Universität Lausanne - LA
Hauptdisziplin Andere Gebiete der Umweltwissenschaften
Beginn/Ende 01.10.2010 - 31.03.2014
Bewilligter Betrag 217'726.00
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Alle Disziplinen (5)

Disziplin
Andere Gebiete der Umweltwissenschaften
Umweltforschung
Umwelttoxikologie
Klinische Pharmakologie
Genetik

Keywords (14)

Ecotoxicology; Ecopharmacology; Anticancer drugs; Proteomics; Drug residues; Daphnids; Environment; Water protection; Ecology; Toxicology; hormones; pollution; Daphnia; Ecotoxicoproteomics

Lay Summary (Englisch)

Lead
Lay summary
Pharmaceutical compounds released from individuals receiving drug treatments can be traced in the aquatic environment (rivers, lakes, groundwater and seashores). Some of them, such as hormone derivatives and antibiotics, have been shown to affect the fauna and flora. While being less abundant than common agricultural or industrial pollutants, drug residues carry specific pharmacological activities susceptible to interact with biological processes even at low concentrations. This problem is likely to expand, due to advances in medicinal therapy. In particular, recent progress in cancer treatment is increasingly associated with the long-term use of new anticancer agents, which have received little attention regarding their effects on living organisms in the environment. In line with their mechanism of action, they are susceptible to induce subtle genetic and cell cycle changes in aquatic fauna and flora under chronic exposure. The main goal of our project is to study daphnids as a model organism responding to the chronic stress caused by residual concentrations of various anticancer agents. We will determine the exposure levels associated not with acute toxicity, but with long-term effects affecting population renewal over several generations. This will necessitate long-lasting (several months), multigenerational toxicological tests, which cannot easily be used to monitor water samples drawn from the environment on a large scale. Therefore, we will associate our tests with the detection of early proteomic signals able to predict these long-term effects: concretely, we will identify one or several proteins showing altered expression in the daphnids destined to progressively suffer from chronic exposure to the pharmaceutical agents. This will help to both develop a rapid response test useful for environmental monitoring, and to elucidate the mechanisms through which anticancer drug residues may affect living organisms that play a key role in aquatic ecosystems. This research addresses emerging environmental concerns associated with contamination by pharmaceuticals. By improving both the practicability and the relevance of pharmaceutical pollution assessment, it might encourage the environment-aware development of drugs in terms of eco-conception, biodegradation and environmental risk, to which major pharmaceutical companies have expressed their commitment.
Direktlink auf Lay Summary Letzte Aktualisierung: 21.02.2013

Verantw. Gesuchsteller/in und weitere Gesuchstellende

Mitarbeitende

Name Institut

Publikationen

Publikation
Multigenerational effects of the anticancer drug tamoxifen and its metabolite 4-hydroxy-tamoxifen on Daphnia pulex.
Borgatta Myriam, Waridel Patrice, Decosterd Laurent-Arthur, Buclin Thierry, Chèvre Nathalie (2016), Multigenerational effects of the anticancer drug tamoxifen and its metabolite 4-hydroxy-tamoxifen on Daphnia pulex., in The Science of the total environment, 545-546, 21-9.
Shotgun ecotoxicoproteomics of Daphnia pulex: biochemical effects of the anticancer drug tamoxifen
BORGATTA Myriam, HERNANDEZ Céline, DECOSTERD Laurent Arthur, CHEVRE Nathalie, WARIDEL Patrice (2015), Shotgun ecotoxicoproteomics of Daphnia pulex: biochemical effects of the anticancer drug tamoxifen, in Journal of Proteome Research, 14(1), 279-291.
The anticancer drug metabolites endoxifen and 4-hydroxy-tamoxifen induce toxic effects on Daphnia pulex in a two-generation study
BORGATTA Myriam, DECOSTERD Laurent Arthur, WARIDEL Patrice, BUCLIN Thierry, CHEVRE Nathalie (2015), The anticancer drug metabolites endoxifen and 4-hydroxy-tamoxifen induce toxic effects on Daphnia pulex in a two-generation study, in Science of The Total Environment, 520, 232-240.

Wissenschaftliche Veranstaltungen

Aktiver Beitrag

Titel Art des Beitrags Titel des Artikels oder Beitrages Datum Ort Beteiligte Personen
SETAC Europe 23nd Annual Meeting, Glasgow 2013 Poster Are anticancer drug metabolites toxic to Daphnia pulex after chronic exposures? 22.05.2013 Glasgow, Grossbritannien und Nordirland Borgatta Myriam; Chèvre Nathalie;
Participation active, 6th SETAC World Congress / SETAC Europe 22nd Annual Meeting Poster Acute and chronic tests of Tamoxifen and its metabolites on Daphnia pulex 22.05.2012 Berlin , Deutschland Borgatta Myriam; Chèvre Nathalie;
SETAC Europe 21st Annual Meeting Poster Ecotoxicoproteomics tests on Daphnia pulex: preliminary steps 15.05.2011 Milano, Italien Borgatta Myriam; Chèvre Nathalie;


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Abstract

Significant pharmaceutical innovations and progresses have occurred in oncology treatments and patients management. Recent signal transduction inhibitor agents having a strong anti-tumour specificity are able to disrupt signal pathways mediating cancer cell proliferation and efficiently prevent tumour growth. Signal transduction inhibitors include imatinib, sunitinib, nilotinib, dasatinib, sorafenib and other tyrosine kinase blockers currently under investigation. But other chemotherapeutic drugs such as antimetabolites (methotrexate, 5-Fluorouracil), mitotic spindle inhibitors (vincristine, vinorelbine), antibiotic inhibitors of topoisomerases (etoposide, topotecan) etc. are also increasingly used in oncology. As a consequence, cancer patients are living longer, and the amount of consumption of these classes of drugs has grown accordingly. In parallel, the amount of anticancer drug residues released into the environment has increased. Indeed, most anticancer drugs are eliminated by urines or faeces to a significant extent in active form. The parent-drugs or their metabolites then can pass through sewage treatment plants with little degradation. They reach the aquatic environment continuously and can therefore be considered as pseudo-persistent compounds. Considering the high biological activity and the cytotoxic proprerties of these drugs, it is surprising that the long-term impact of these substances on aquatic organisms remains largely unknown.The aquatic biocoenosis is continuously and increasingly exposed to such substances, and we hypothesize that this may cause long-term deleterious effects at the population level. Adverse effects on future generations of common species have to be detected as soon as possible for the preservation of the aquatic community. We propose to carry out eotoxicity tests with the water flea Daphnia pulex, which will help us to find early evidence of chronic stress on sensitive aquatic organisms due to pharmaceuticals. Whole life-cycle exposure and multigenerational effects will be considered in this project. We propose to use daphnids as model organism for multigenerational effects since they have a long history of model organisms in ecology, evolution and environmental studies, and their biology has recently been extensively characterized.Such multigenerational tests are however costly to perform, and in parallel it would be important to develop biomarkers allowing for “early warning” detection of deleterious effects of anticancer drugs. In this study, we propose to investigate how new proteomics approach could contribute to detect cellular damage in organisms exposed to sublethal levels. To this end, we will study the changes at the protein level in cells or organisms exposed to anti-cancer drugs to better understand their toxicological mechanisms and their potential effects on aquatic invertebrates. Proteomics will therefore be used in environmental toxicology to find ecotoxicological markers at the protein level. While the classical biomarkers of cytotoxic or genotoxic effects are appropriate for mutagenic chemotherapeutic agents, they are not sufficient for assessing the impact of agents targeted to proteins, such as the antimetabolites the new signal transduction inhibitors, on bioindicator organisms. There is indeed a need to take into account different levels of biological organization for a comprehensive evaluation of the environmental effects of pollutants. Thus, our project will first measure the effects on daphnids used as model organisms, and then determine new proteomic biomarkers with aquatic pseudo-persistent compounds, such as anticancer drugs. The use of early warning biomarkers as a tool for better water control will help to reinforce and simplify monitoring programs. Thereby, our project fits well with the current role of environmental management to protect ecosystems and their inhabitants.
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