CYP1B1 knockdown does not alter synergistic developmental toxicity of polycyclic aromatic hydrocarbons in zebrafish (Danio rerio).
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.
Timme-Laragy
Alicia R
AR
Nicholas School of the Environment and Earth Sciences and Integrated Toxicology and Environmental Health Program, Duke University, Durham, NC, USA.
Noyes
Pamela D
PD
Buhler
Donald R
DR
Di Giulio
Richard T
RT
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*
D011084:Polycyclic Aromatic Hydrocarbons; D014874:Water Pollutants, Chemical; D001189:Aryl Hydrocarbon Hydroxylases; D065633:Cytochrome P-450 CYP1B1