Activity of Phase I and Phase II enzymes of the benzo[ a]pyrene transformation pathway in zebrafish ( Danio rerio) following waterborne exposure to arsenite

Abstract

The environmental pollutants inorganic arsenic (iAs) and benzo[ a]pyrene (B[ a]P) are carcinogens often found together in groundwater. The hepatic metabolism of B[ a]P is a multi-step process requiring several Phase I and Phase II enzymes, notably cytochrome p450 1A (CYP1A), epoxide hydrolase (EH), and glutathione S-transferase (GST). The purpose of this study was to examine the effect of arsenite (As(III)) on the activity of these enzymes in vivo utilizing adult zebrafish ( Danio rerio). Zebrafish were exposed to either 0.4 μM B[ a]P, 0.4 μM B[ a]P + 0.4 μM As(III), 0.4 μM B[ a]P + 8 μM As(III), 0.4 μM As(III), or 8 μM As(III) for 7 days. Co-exposures to As(III) and B[ a]P led to significant decreases in CYP1A enzyme activity (approximately 3-fold) when compared to exposure to B[ a]P alone. No similar effects occurred with EH or GST, although B[ a]P exposure did significantly increase EH activity. Furthermore As(III) and B[ a]P co-exposures significantly decreased CYP1A transcript levels (up to 35-fold) when compared to B[ a]P. However, B[ a]P-induced CYP1A protein levels remained elevated following co-exposures to As(III). This evidence suggests that As(III) has the potential to modify components of the B[ a]P biotransformation pathway in vivo via a disruption of CYP1A activity by way of both pre- and post-translational mechanisms.