1. Sponsor Organization: NIH/NIEHS

2. Project Title: 07009-03 TCDD DEPENDENT REGULATION OF THYMUS DEVELOPMENT

3. Project Focus:

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

4. Description:

Many of the toxic responses to TCDD (particularly in targets such as the skin and the immune system) are a consequenced of altered growth and differentiation, presumably mediated by the Ah receptor-dependent control of the expression of specific growth regulatory and differentiation genes. Previous studies from this laboratory have shown that TCDD induces terminal differentiation in cultures of normal human keratinocytes and blocks the thymic epithelial cell (TEC)-dependent maturation of prothymocytes in vitro. Subsequent research by others confirms that TCDD affects thymocyte maturation in vivo and suggests that thymic epithelium is altered by in vivo exposure to TCDD. The proposed research using early gestation C57BL/6 and neonatal SCID mice, and fetal thymic organ cultures as models will examine the role of the Ah receptor and its battery of known differentiation and growth regulatory genes in the development and function of the thymic microenvironment (TME). Cloning strategies will be implemented in these thymus developmental models to identify novel TCDD-responsive developmental genes. A detailed study of the molecular biology of TCDD actions on the development and function of the epithelial component of the TME should provide a prototype model for other developmental targets and new information on the biological function of the Ah receptor system.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary:
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Mammal
  • Mice
• Study Type:
  • In Vitro
  • In Vivo
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
• Hormonal Measures:
  • Ah Receptor, Molecular
• Level Of Study:
  • Gene Expression
• Chemistry Metabolism:
• Life Stage:
• Risk Assessment:

10. Chemical Agents:

• Dioxins

11. Performing Institution:

• UNIVERSITY OF MASSACHUSETTS MEDICAL SCH

12. Contact:

Edit (password needed)