Modulation of 17β-estradiol induced estrogenic responses in male goldfish (Carassius auratus) by benzo[a]pyrene and ketoconazole

The aquatic environment is challenged with complex mixtures of chemicals that may interact biochemically with each other in non-target aquatic organisms through a combination of actions, resulting in unpredictable mixture toxicity. This study focuses on the interactive effects of chemicals, including benzo(a)pyrene (BaP) and ketoconazole (KCZ), on 17 beta-estradiol (E2)-induced estrogenic responses in male goldfish (Carassius auratus). The possible interactions between BaP or KCZ and E2 were investigated on the expression of cytochromeP4501A (CYP1A, biotransformation enzyme) and on its corresponding catalytic activity 7-ethoxyresorufin-O-deethylase (EROD activity), as well as on the expression of CYP19 (steroidogenic enzyme) and E2 bioaccumulation in liver. Exposure to E2 caused a significant increase in estrogenic responses corresponding with the E2 bioaccumulation. When comparing results to the E2 exposure group, co-exposure to BaP resulted in an increase in the cyp1a mRNA expression and its corresponding EROD activity and a marked decrease in the E2 bioaccumulation, but the expression of aromatase was not altered. Conversely, co-treatment with KCZ significantly suppressed the E2-modulated expression of metabolism and synthesis enzymes, which were accompanied by an increase in the E2 bioaccumulation. These data suggest that the modulation of E2-induced estrogenic responses by BaP and KCZ were correlated to the alterations of E2 bioaccumulation in goldfish, leading to a combination of changes in the capacity of biotransformation and steroidogenesis. The complex interactions between chemicals with different modes of actions highlight the need for caution in determining the safety of combined pollution in the aquatic environment.