title: CYP1B1 knockdown does not alter synergistic developmental toxicity of polycyclic aromatic hydrocarbons in zebrafish (Danio rerio).
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.
authors: Nicholas School of the Environment and Earth Sciences and Integrated Toxicology and Environmental Health Program, Duke University, Durham, NC, USA.
authors: Alicia R
authors: AR
authors: Timme-Laragy
authors: Pamela D
authors: PD
authors: Noyes
authors: Donald R
authors: DR
authors: Buhler
authors: Richard T
authors: RT
authors: Di Giulio
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000172:deficiency* / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000196:embryology; D047108:Embryonic Development / Q000187:drug effects*; D048788:Growth and Development; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*
chemical_list: D011084:Polycyclic Aromatic Hydrocarbons; D014874:Water Pollutants, Chemical; D001189:Aryl Hydrocarbon Hydroxylases; D065633:Cytochrome P-450 CYP1B1