The environmental toxin and carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin 
(TCDD, dioxin) binds and activates the transcription factor aryl hydrocarbon 
receptor (AHR), inducing CYP1 family cytochrome P450 enzymes. CYP1A2 and its 
avian ortholog CYP1A5 are highly active arachidonic acid epoxygenases. 
Epoxygenases metabolize arachidonic acid to four regioisomeric 
epoxyeicosatrienoic acids (EETs) and selected monohydroxyeicosatetraenoic acids 
(HETEs). EETs can be further metabolized by epoxide hydrolases to 
dihydroxyeicosatrienoic acids (DHETs). As P450-arachidonic acid metabolites 
affect vasoregulation, responses to ischemia, inflammation, and metabolic 
disorders, identification of their production in vivo is needed to understand 
their contribution to biologic effects of TCDD and other AHR activators. Here we 
report use of an acetonitrile-based extraction procedure that markedly increased 
the yield of arachidonic acid products by lipidomic analysis over a standard 
solid-phase extraction protocol. We show that TCDD increased all four EETs 
(5,6-, 8,9-, 11,12-, and 14,15-), their corresponding DHETs, and 18- and 20-HETE 
in liver in vivo and increased 5,6-EET, the four DHETs, and 18-HETE in heart, in 
a chick embryo model. As the chick embryo heart lacks arachidonic 
acid-metabolizing activity, the latter findings suggest that arachidonic acid 
metabolites may travel from their site of production to a distal organ, i.e., 
heart. To determine if the TCDD-arachidonic acid-metabolite profile could be 
altered pharmacologically, chick embryos were treated with TCDD and the soluble 
epoxide hydrolase inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA). 
Cotreatment with AUDA increased hepatic EET-to-DHET ratios, indicating that the 
in vivo profile of P450-arachidonic acid metabolites can be modified for 
potential therapeutic intervention.