Global characterization of dose-dependent effects of cadmium in clam Ruditapes philippinarum

Cadmium (Cd) is being frequently detected in marine organisms. However, dose-dependent effects of Cd challenged unraveling the toxicological mechanisms to organisms and developing biomarkers. Here, on clams Ruditapes philippinarum following exposure 5 doses (3, 9, 27, 81, 243 μg/L) were investigated using benchmark dose (BMD) method. By model fitting, calculation BMD values was performed transcriptomic profiles, metals concentrations, antioxidant indices. induced not only significant accumulation clams, but also marked alterations essential such as Ca, Cu, Zn, Mn, Fe. Gene regulation posed little influence metal homeostasis, indicated by poor enrichment differentially expressed genes (DEGs) associated with binding transport lower concentrations Cd-treated groups. analysis biological processes pathways showed that peptide cross-linking most sensitive process exposure, followed focal adhesion, ubiquitin mediated proteolysis, apoptosis. Occurrence apoptosis confirmed TUENL-positive staining gills hepatopancreas treated Cd. Furthermore, many DEGs, transglutaminases (TGs), metallothionein (MT), STEAP2-like laccase, which presented linear or monotonic curves relatively low values, potentially preferable biomarkers Overall, biochemical endpoints unraveled sensitiveness key events response treatments, provided new insights exploring well biomarker selection.