1. Sponsor Organization: NIH/NIEHS

2. Project Title: 03606-12 ARACHIDONATE PRODUCTS IN DIOXIN AND PCB TOXICITY

3. Project Focus:

• Project Primary Focus: Human Health Effects
• Project Secondary Focus:

4. Description:

TCDD and chemically related PCBs are of continuing public concern because of their high toxicity for some species. This laboratory is investigating the novel hypothesis that TCDD-induced P450 participates in TCDD toxicity by metabolizing endogenous compounds, such as the membrane fatty acid, arachidonic acid (AA) to biologically active metabolites that can affect cell signals and thereby modulate toxicity. We will continue to use principally a well established chick embryo model. TCDD treatment was found to increase metabolism of AA by P450 to specific AA epoxides and monohydroxylated products with biologic activities resembling changes in TCDD toxicity. TCDD increases AA epoxides by a specific TCDD-induced P450, TCDD/AA, distinct from the TCDD induced P-450 catalyzing AHH and 7- EROD, TCDD/AHH. TCDD treatment also increases AA release from liver cells, making AA available to TCDD/AA and depresses formation of constitutive omega-OH AA. We will investigate the mechanisms behind these changes and the increase by TCDD treatment in [Ca2+]/i and their consequences for cell function.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Basic Research
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
• Study Type:
  • In Vivo
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
• Hormonal Measures:
• Level Of Study:
  • Gene Expression
  • Ah Receptor
• Chemistry Metabolism:
  • Toxicokinetics
  • Tissue Residue
  • Xenobiotic Metabolism
• Life Stage:
• Risk Assessment:

10. Chemical Agents:

• Dioxins

11. Performing Institution:

• CORNELL UNIVERSITY MEDICAL CENTER

12. Contact:

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