title: Mechanisms of TCDD-induced abnormalities and embryo lethality in white leghorn chickens.
abstract: The toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds in birds has been well-established in laboratory and field studies. Observed effects of TCDD and related chemicals in birds include developmental deformities, reproductive failure, liver damage, wasting syndrome and death. The mechanism of action of TCDD at the cellular level is primarily mediated through the aryl hydrocarbon receptor (AhR). However, the mechanism of toxic action at the organism level is poorly understood. In this study, the role of radical oxygen species and mixed function oxidize (MFO; cytochrome P4501A) in the mechanism of TCDD-induced abnormalities and lethality were examined by co-injecting radical scavengers and an MFO inhibitor (piperonyl butoxide). Egg injection studies were conducted to determine if in ovo TCDD exposure can cause oxidative stress in white leghorn chicken eggs. Test agents were injected into the yolk prior to incubation. Treatments included TCDD (150 ng/kg), triolein (vehicle control), and various co-treatments including MnTBAP (a mimetic of superoxide dismutase), piperonyl butoxide, piroxicam, vitamin A acetate, and vitamin E succinate. Phenytoin, which is known to cause teratogenesis through oxidative stress was used as a positive control. Eggs were incubated until hatch and then the following parameters were assessed: mortality, hatching success, abnormalities, weights for whole body, liver, heart and brain, and biochemical endpoints for oxidative stress. As a measure of exposure, concentrations of TCDD and ethoxyresorufin-O-deethylase (EROD) activities were measured in tissues of hatchlings. While greater mortality and abnormalities were observed in the TCDD treatment groups, the number of the replicates were not great enough to detect statistically significant differences in abnormality rates for the co-treatments. Some of the observed developmental abnormalities included edema, liver necrosis and bill, eye and limb deformities with TCDD treatments, bill and brain deformities with phenytoin treatments, eye abnormalities with Vitamin E treatments, and abnormal feather pigmentation with piperonyl butoxide treatments.
authors.affiliation: National Food Safety and Toxicology Center, Department of Zoology, Institute for Environmental Toxicology, Michigan State University, East Lansing, MI, USA. ablankenship@entrix.com
authors.forename: A L
authors.initials: AL
authors.lastname: Blankenship
authors.forename: K
authors.initials: K
authors.lastname: Hilscherova
authors.forename: M
authors.initials: M
authors.lastname: Nie
authors.forename: K K
authors.initials: KK
authors.lastname: Coady
authors.forename: S A
authors.initials: SA
authors.lastname: Villalobos
authors.forename: K
authors.initials: K
authors.lastname: Kannan
authors.forename: D C
authors.initials: DC
authors.lastname: Powell
authors.forename: S J
authors.initials: SJ
authors.lastname: Bursian
authors.forename: J P
authors.initials: JP
authors.lastname: Giesy
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D002642:Chick Embryo / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism; D002645:Chickens; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004338:Drug Combinations; D020964:Embryo Loss / Q000139:chemically induced*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005298:Fertility / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010574:Pesticide Synergists / Q000494:pharmacology; D010882:Piperonyl Butoxide / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D013723:Teratogens / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*
chemical_list: D004338:Drug Combinations; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D010574:Pesticide Synergists; D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens; D006899:Mixed Function Oxygenases; D019363:Cytochrome P-450 CYP1A1; D010882:Piperonyl Butoxide