Genotoxic Effect and Carcinogenic Potential of a Mixture of As and Cd in Zebrafish at Permissible Maximum Contamination Levels for Drinking Water
2016
Doganlar, Oguzhan | Doganlar, Zeynep Banu | Muranlı, Fulya Dilek Gokalp | Guner, Utku
Currently, the toxic effects and carcinogenic potential of individually treated arsenic (As) or cadmium (Cd) are well documented both in animal and human tissues. However, there are no data focusing on the genotoxicity of these heavy metals as a mixture at the very low concentrations of permissible limits for drinking water. In this study, we examine the genotoxicity and carcinogenic potential of single and combined treatments of As and Cd, as well as attempt to elucidate the mechanism of action of certain cell defense systems such as antioxidants, gene repair, heat shock, cell cycle control, and the apoptosis pathway. Zebrafish (Danio rerio), reared under controlled conditions with artificial diets, were treated with As and Cd, either individually or in combination, at concentrations commonly found in water (10 ppb for As and 5 ppb for Cd) and tenfold higher concentrations for 48 h. Our results indicate that separately, As and Cd treatments at low dose selectively induce antioxidant enzymes, gene repair, and caspase-independent apoptosis in gill tissue, by targeting the mitochondria, leading to oxidative stress and sub-lethal levels of DNA damage. However, tenfold higher (100 ppb As + 50 ppb Cd) treatment caused significant downregulation of genes involved in double-strand break repair and molecular chaperone genes. Additionally, the highest BCL2/BAX ratio (1.6) and lowest expression levels of caspase-3 (8.4-fold) in all treated groups were observed in same condition. These results demonstrate that both single and combined exposure to As and Cd at permissible levels is potentially safe and causes repairable genotoxicity in gill tissue. However, the highest concentration is potentially carcinogenic due to ineffective DNA repair and insufficient apoptosis.
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