1. Sponsor Organization: NIH/NIEHS

2. Project Title: 06995-03 TOXICITY OF ENVIRONMENTAL ESTROGENS

3. Project Focus:

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

4. Description:

Our ultimate goal is to determine how developmental exposure to toxicants that utilize nuclear receptor systems (e.g., TCDD, peroxisomeproliferators, retinoids, environmental estrogens, etc.) disrupts gene expression and produces resultant cellular defects. This proposal focuses on the mechanism by which one such toxicant (diethylstilbestrol or DES) alters expression of the c-fos protooncogene in the reproductive tract of developing rodents. Using this established in vivo model for human exposure to environmental estrogens, including the in utero exposure of humans to DES in the l96Os, we have obtained preliminary data that DES causes a persistent induction of c-fos expression in the reproductive tracts of both male and female animals. These observations led to our HYPOTHESIS that developmental exposure to estrogens causes epigenetic changes in the structure of the c-fos protooncogene to alter its expression and thereby disrupt the normal function of target cells.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Basic Research
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Mammal
  • Rodents
  • In Utero
• Study Type:
  • In Vitro
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
  • Reproductive
• Hormonal Measures:
• Level Of Study:
  • Carcinogenesis, Molecular
• Chemistry Metabolism:
• Life Stage:
  • Female
  • Male
• Risk Assessment:

10. Chemical Agents:

• Estrogens/Anti-Estrogens
• Des

11. Performing Institution:

• UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

12. Contact:

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