PUBLICATION
Activity of Phase I and II Enzymes of the Benzo[a]pyrene Transformation Pathway in Zebrafish (Danio rerio) Following Waterborne Exposure to Arsenite
- Authors
- Thompson, E.D., Burwinkel, K.E., Chava, A.K., Notch, E.G., and Mayer, G.D.
- ID
- ZDB-PUB-100621-12
- Date
- 2010
- Source
- Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 152(3): 371-378 (Journal)
- Registered Authors
- Keywords
- Arsenic, Benzo[a]pyrene, Cytochrome p4501A, Epoxide hydrolase, Enzyme activity, Expression
- MeSH Terms
-
- Arsenites/metabolism
- Arsenites/toxicity*
- Drug Interactions
- Zebrafish/metabolism*
- Metabolic Detoxication, Phase I*
- Water Pollutants, Chemical/metabolism
- Water Pollutants, Chemical/toxicity
- Biotransformation
- Animals
- Benzo(a)pyrene/metabolism*
- Benzo(a)pyrene/toxicity
- Cytochrome P-450 CYP1A1/genetics
- Cytochrome P-450 CYP1A1/metabolism
- Metabolic Detoxication, Phase II*
- Carcinogens/metabolism*
- Carcinogens/toxicity*
- PubMed
- 20547244 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.
- CTD
- 20547244
Citation
Thompson, E.D., Burwinkel, K.E., Chava, A.K., Notch, E.G., and Mayer, G.D. (2010) Activity of Phase I and II Enzymes of the Benzo[a]pyrene Transformation Pathway in Zebrafish (Danio rerio) Following Waterborne Exposure to Arsenite. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. 152(3):371-378.
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 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 0.4muM B[a]P, 0.4muM B[a]P+0.4muM As(III), 0.4muM B[a]P+8muM As(III), 0.4muM As(III), or 8muM As(III) for 7days. 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping