Environmentally relevant fluoride alters nuclear integrity in erythrocytes and induces DNA damage in hepatocytes of zebrafish

Abstract

The toxicity associated with environmentally relevant concentration of fluoride (F) was investigated in zebrafish (Danio rerio). Following exposure to 15 ppm sodium fluoride (NaF; 6.8 ppm F-), a concentration reported to be present in potable water in different parts of the world, the erythrocytes developed micronuclei and other nuclear anomalies including blebbed, lobed and notched nuclei. F exposure also elicited marked cytoxicity in the hepatocytes in trypan blue dye exclusion test and acridine orange/ ethidium bromide (AO/EtBr) staining. There was upregulation of reactive oxygen species (ROS) generation in the hepatocytes of F-treated fishes, and DNA fragmentation assay revealed compromised nuclear integrity as evident from the smear formation following F exposure. DNA strand scission assay using calf thymus DNA, however, did not show any DNA damage post-F exposure, suggesting that the genotoxic effect was perhaps mediated through ROS generation. Up-regulation of p53, Bax, caspase 9 and caspase 3 gene expressions with concomitant downregulation of anti-apoptotic Bcl-2 gene in treated fishes confirmed the induction of intrinsic apoptotic pathway due to F exposure. The study confirms the toxicity of environmentally relevant concentration of F to aquatic creatures.