title: The mining chemical Polydadmac is cytotoxic but does not interfere with Cu-induced toxicity in Atlantic salmon hepatocytes.
abstract: To speed up sedimentation of suspended solids the mining industry often uses flocculent chemicals. In this work we evaluated the cytotoxic and mechanistic effects of Polydadmac, and its basic component Dadmac, on fish cells. Dose-response effects, temperature-dependent effects and impact of Dadmac and Polydadmac on Cu toxicity were studied in Atlantic salmon hepatocytes. We used the xCELLigence system and the MTT test for cytotoxicity assessments, and real-time RT-qPCR to evaluate molecular effects. The results showed a cytotoxic response for Polydadmac but not for Dadmac. Elevated levels of Cu were cytotoxic. Moderately cytotoxic concentrations of Cu (100-1000 μM) induced significant responses on the transcription of a number of genes in the cells, i.e. cuznsod (sod1), cat, mnsod (sod2), nfe2l2, hmox1, mta, casp3b, casp6, bclx, cyp1a, ccs, atp7a, app, mmp13, esr1, ppara, fads2 and ptgs2. A factorial PLS regression model for mnsod transcription showed a synergistic effect between Dadmac and Cu exposure in the cells, indicating an interaction effect between Dadmac and Cu on mitochondrial ROS scavenging. No interaction effects were seen for Polydadmac on Cu toxicity. In conclusion, Polydadmac is cytotoxic at elevated concentrations but appears to have low ability to interfere with Cu toxicity in Atlantic salmon liver cells.
authors.affiliation: National Institute of Nutrition and Seafood Research, N-5817 Bergen, Norway. Electronic address: pal.olsvik@nifes.no.
authors.forename: Pål A
authors.initials: PA
authors.lastname: Olsvik
authors.affiliation: National Institute of Nutrition and Seafood Research, N-5817 Bergen, Norway.
authors.forename: Marc H G
authors.initials: MH
authors.lastname: Berntssen
authors.affiliation: National Institute of Nutrition and Seafood Research, N-5817 Bergen, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Waagbø
authors.affiliation: National Institute of Nutrition and Seafood Research, N-5817 Bergen, Norway; EWOS AS, N-5803 Bergen, Norway.
authors.forename: Ernst
authors.initials: E
authors.lastname: Hevrøy
authors.affiliation: National Institute of Nutrition and Seafood Research, N-5817 Bergen, Norway.
authors.forename: Liv
authors.initials: L
authors.lastname: Søfteland
mesh_terms: D000064:Acclimatization; D000818:Animals; D003300:Copper / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects*; D008297:Male; D008906:Mining; D011095:Polyethylenes / Q000633:toxicity*; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D020317:Salmo salar; D013696:Temperature
chemical_list: D011095:Polyethylenes; D000644:Quaternary Ammonium Compounds; C041004:poly-N,N-dimethyl-N,N-diallylammonium chloride; D003300:Copper
keywords: Environmental pollution; Fish; Mining activity; Polydadmac; Processing chemicals; Transcriptional responses