PUBLICATION
CYP1B1 knockdown does not alter synergistic developmental toxicity of polycyclic aromatic hydrocarbons in zebrafish (Danio rerio)
- Authors
- Timme-Laragy, A.R., Noyes, P.D., Buhler, D.R., and Di Giulio, R.T.
- ID
- ZDB-PUB-080408-10
- Date
- 2008
- Source
- Marine Environmental Research 66(1): 85-87 (Journal)
- Registered Authors
- Buhler, Donald R.
- Keywords
- Polycyclic aromatic hydrocarbons, Zebrafish, CYP1B1, CYP1A
- MeSH Terms
-
- Animals
- Aryl Hydrocarbon Hydroxylases/deficiency*
- Aryl Hydrocarbon Hydroxylases/genetics
- Cytochrome P-450 CYP1B1
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/embryology
- Embryonic Development/drug effects*
- Growth and Development
- Polycyclic Aromatic Hydrocarbons/toxicity*
- Water Pollutants, Chemical/toxicity*
- Zebrafish/embryology*
- Zebrafish/genetics*
- PubMed
- 18378296 Full text @ Mar. Environ. Res.
Citation
Timme-Laragy, A.R., Noyes, P.D., Buhler, D.R., and Di Giulio, R.T. (2008) CYP1B1 knockdown does not alter synergistic developmental toxicity of polycyclic aromatic hydrocarbons in zebrafish (Danio rerio). Marine Environmental Research. 66(1):85-87.
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are contaminants increasing in the environment largely due to burning of fossil fuels. Our previous work identified a synergistic toxicity interaction in zebrafish embryos occurring when PAHs that are agonists for the aryl hydrocarbon receptor (AHR) co-occur with PAHs that are CYP1A inhibitors. This toxicity is mediated by the AHR2, and morpholino knockdown of CYP1A exacerbated toxicity. This study tested two hypotheses: (1) in the absence of functional CYP1A, metabolism of PAHs is shunted towards CYP1B1, which has been shown in mammals to produce more reactive metabolites of PAHs; alternatively, (2) CYP1B1 serves a protective role similar to CYP1A. We used a morpholino approach to knockdown CYP1B1 alone and in co-knockdown with CYP1A to determine whether we could alter deformities caused by synergistic toxicity of PAHs. CYP1B1 knockdown was not different from non-injected controls; nor were CYP1B1+CYP1A co-knockdown deformities different from CYP1A knockdown alone. These data suggest that CYP1B1 is not a significant factor in causing synergistic toxicity of PAHs, nor, in contrast to CYP1A, in providing protection
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping