Effects of Ifosfamide and Cisplatin Exposure Combined with a Climate Change Scenario on the Transcriptome Responses of the Mussel Mytilus Galloprovincialis

Abstract

Coastal ecosystems are currently exposed to pollutants and climate changes. Namely, the increasing consumption of antineoplastics drugs and their potential release to aquatic ecosystems are raising concerns. Nevertheless, information regarding the toxicity of these drugs towards non-target species is scarce, especially considering climate change scenarios. Ifosfamide (IF) and cisplatin (CDDP) are among the antineoplastics already detected in aquatic compartments and due to their mode of action (MoA) can negatively affect aquatic organisms. Thia study evaluates the transcription of target genes related to the MoA of IF and CDDP in Mytillus galloprovincialis exposed to environmental relevant low concentrations of these drugs, under an actual (17 ºC) and predicted warming scenario (21 ºC). Results showed an upregulation of the cyp4y1 gene when exposed to the highest concentrations of IF, regardless of the temperature. Both drugs upregulated genes related to DNA damage and apoptosis (p53, caspase 8 and gadd45), especially in warmer conditions. Increased temperature also downregulated genes related to stress and immune responses (krs and mydd88). Therefore, the present results showed that antineoplastics combined with temperature alterations can affect transcriptomic responses of M. galloprovincialis, by changing their sensitivity towards these drugs.

Keywords: Anticancer drugs, Bivalves, Transcriptomic, Genetic expression, climate change