Application of Microarray Technology to Toxicity Evaluation in Wild Common Cormorants Contaminated with Persistent Organic Pollutants

In our previous studies, we have demonstrated that common cormorants (Phalacrocorax carbo) inhabiting Lake Biwa, Japan are contaminated with various chemicals, such as dioxins and related compounds (DRCs), organochlorines, organotins, brominated flame retardants, and perfluorinated compounds (PFCs). Since wild cormorants are exposed to these compounds simultaneously, mixture toxicities of them are of concern. To understand the potential toxic effects of these contaminants, we constructed an oligo array and analyzed the gene expression profiles in common cormorant livers. The data revealed that the expression levels of 29 genes, functionally categorized in xenobiotics metabolizing enzymes, immune function, and antioxidant system, were significantly correlated with total 2,3,7,8tetrachlorodibenzo-p-dioxin toxic equivalent (TEQ) levels. In addition, we identified 55 gene expressions associated with perfluorooctanesulfonate (PFOS) levels. The accumulation of PFOS affected the genes related to molecular chaperones, intracellular trafficking, secretion, vesicular transport and cell wall/membrane/envelope biogenesis. Furthermore, multiple regression analyses identified seven significant models, in which certain genes showed expression levels altered by accumulation of PFCs and DRCs. The regression models explained associations among cytochrome P450 1A mRNA and protein expression levels, and its catalytic activity, ethoxyresorufin-O-deethylase as a function of both perfluorononanoic acid and the TEQ levels. Thus, the regression models suggested the potential of PFCs to enhance toxicities of DRCs. Since mixture toxicity is an urgent issue, further study is required to understand the effects of mixtures of PFCs and DRCs in wild cormorants.