Oxidative DNA damage may not mediate Ni-induced genotoxicity in marine mussels: Assessment of genotoxic biomarkers and transcriptional responses of key stress genes

•Ni is a priority aquatic pollutant with little understood genotoxicity.•Mussels exposed to 0–3600μgL−1 Ni for 5 days; genotoxic to haemocytes at ≥1800μgL−1.•No significant oxidative DNA damage to haemocyte at genotoxic Ni concentrations.•gst, mt20 and pgp genes overexpressed in gill tissue in response to Ni.•First study indicating a role for MXR in Ni detoxification in mussels. Nickel (Ni) is a known carcinogenic and mutagenic compound and an important contaminant of aquatic environments. Ni toxicity and its potential impact on aquatic organisms are, however, not well understood. This study used an integrated approach to evaluate genotoxic effects, tissue-specific accumulation and transcriptional profiles of key genes in mussels, Mytilus galloprovincialis, exposed to a range of concentrations of Ni. The genotoxic effects assessed were total and oxidative DNA damage (DNA strand breaks measured using the enzyme modified comet assay), and induction of micronuclei (MN; clastogenic and/or aneugenic effects) using haemocytes as the target cells. Six genes (pgp, mt10, mt20, sod, hsp70 and gst) were selected for transcriptional analysis in the gills based on their key role in the stress response. Following exposure to sublethal concentrations of Ni (0–3600μgL−1) for 5 days, mussel haemocytes showed significant genotoxicity at >1800μgL−1 (4-fold increase for DNA strand breaks and 3-fold increase for MN induction). There was no significant difference between buffer (control) and enzyme treatments which target oxidised DNA bases (formamidopyrimidine glycosylase or endonuclease IIII). This suggested that, in haemocytes, oxidative DNA damage is not a major mechanism for Ni-induced genotoxicity. The expression of mt20 and gst genes in gill was up-regulated at genotoxic concentrations, whilst pgp expression was markedly up-regulated, particularly at 18μgL−1 Ni (19-fold increase). Pearson's correlation analysis revealed significant associations between % tail DNA and MN induction in haemocytes (r=0.88, p