Mixture effects of arsenic and chromium on erythrocytic nuclear abnormalities and expression of DNA repair, tumor suppressor and apoptotic genes in liver of zebrafish.

The present study investigated the individual and mixture effects of Arsenic (As) and Chromium (Cr) at their environmental concentrations in zebrafish (Danio rerio). After 15, 30 and 60 days of exposure, increased frequencies of erythrocytic nuclear abnormalities (ENAs) were noticed. After 60 days of exposure, DNA damage was observed in liver and base excision DNA repair (BER) and mismatch DNA repair (MMR) pathways were studied to know the cellular responses. Altered expression of BER (ogg1, apex1, creb1, polb) and MMR (mlh1, msh2, msh6) genes indicated inhibition of DNA repair. Downregulation of tumor suppressor genes (p53 and brca2) occurred in mixture group. Downregulation of bax, caspase9 and decreased bax/bcl2 ratio indicated prevention of intrinsic apoptotic pathway in treated groups. Results indicated As and Cr-induced predisposition to genomic instability and carcinogenesis in zebrafish. Overall, this study confirmed the additive genotoxic effects of As and Cr in zebrafish erythrocytes and in liver after chronic exposure.