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

Myriam Borgatta

Summary of the PhD

Pharmaceutical compounds released from individuals undergoing 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  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, these specific drugs 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 with long-term effects affecting population renewal over several generations. As this purpose calls for long-lasting experiments (several months), such as multigenerational toxicological tests, it cannot be used easily 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 suffer progressively from chronic exposure to 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.