title: 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 microM B[a]P, 0.4 microM B[a]P+0.4 microM As(III), 0.4 microM B[a]P+8 microM As(III), 0.4 microM As(III), or 8 microM 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.
authors.affiliation: Department of Biological Sciences, 204D Natural Science Center, Northern Kentucky University, Highland Heights, KY 41099, USA. thompsone1@nku.edu
authors.forename: E David
authors.initials: ED
authors.lastname: Thompson
authors.forename: Karen E
authors.initials: KE
authors.lastname: Burwinkel
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chava
authors.forename: Emily G
authors.initials: EG
authors.lastname: Notch
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Mayer
mesh_terms: D000818:Animals; D018053:Arsenites / Q000378:metabolism / Q000633:toxicity*; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D018053:Arsenites; D002273:Carcinogens; D014874:Water Pollutants, Chemical; D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1; C015001:arsenite