Cytotoxic responses of the anticancer drug cyclophosphamide in the mussel Mytilus galloprovincialis and comparative sensitivity with human cells lines

the rise of cancer cases worldwide led to an increase in production and consumption of anticancer drugs, that ultimately end up in the marine environment and are accumulated in aquatic organisms. Cyclophosphamide (CP) is a cytotoxic alkylating agent frequently prescribed in cancer treatments. This study assess ecotoxicological effects of CP on mussels Mytilus galloprovincialis, through in vivo and ex vivo approaches and compares the sensitivity of mussel haemocytes with well-established human cell lines (RPE and HeLa). Mussels were exposed in vivo to CP (1000 ng L-1) and several biomarkers analysed in gills and digestive glands namely neurotoxicity (AChE activity), oxidative stress (GPx activity), biotransformation (GST activity), lipid peroxidation (LPO) and apoptosis (caspase activity), whereas genotoxicity was determined in mussels' haemocytes. Cytotoxicity was also assessed in haemocytes (in vivo and ex vivo) and human cell lines (in vitro) exposed to a range of CP concentrations (50, 100, 250, 500 and 1000 ng L-1) over 24 h, via neutral red assay. In in vivo exposure, detoxification of CP did not efficiently occur in the gills while in digestive glands GPx and GST activities were induced, jointly with a decrease in lipid peroxidation, indicating a potential outcome of the protective antioxidant mechanisms, whereas no apoptosis was noted. Moreover, cytotoxicity and DNA damage were detected in haemocytes. the ex vivo exposure haemocytes to CP caused cytotoxicity (from 100 ng L-1), whereas no effects occurred in human cell lines. This suggests that, at relevant environmental concentrations, CP cause subtle and irreversible impacts on M. galloprovincialis. (C) 2020 Elsevier Ltd. All rights reserved.FCTPortuguese Foundation for Science and TechnologyEuropean Commission [UID//00350/2020]project EMERGEMIX [PTDC/BIA-BMA/30922/2017]