1. Sponsor Organization: NIH/NIEHS

2. Project Title: 07273-03 TIMING OF ENVIRONMENTAL CHEMICALS IN BREAST CANCER

3. Project Focus:

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

4. Description:

We havehypothesized that estrogenically-active chemicals can exert predisposition for or against breast cancer, depending on the xenobiotic and timing of exposure. We will investigate the potential of six environmental chemicals during three critical periods of development for altering susceptibility for breast cancer and to investigate two mechanisms that could be predictive indicators of this disease. Sprague Dawley CD rats will be exposed during the prenatal, neonatal and pubertal periods of development to diethylstilbestrol, genistein, l-(o-chlorophenyl)-l-l)p- chlorophenyl)-2,2,2-trichloroethane (o,p'-DDT), Aroclor 1221, Aroclor 1254 and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We will subsequently study cell differentiation in mammary whole mounts and measure cell proliferation using proliferating cell nuclear antigen as a marker of mitotic activity. The maturation of undifferentiated terminal end buds to more differentiated lobules have been shown to yield structures that are less susceptible to DNA damage and replication (2). Likewise, cells that have a higher proliferation index are more susceptible to carcinogens. We will also investigate the effects of these environmental chemicals on pituitary, ovarian and uterine weights as markers of estrogen action and on circulating levels of estrogen, progesterone, prolactin and growth hormone. Finally, we will investigate the potential of selected xenobiotics and developmental windows to alter latency, incidence and multiplicity of DMBA- induced adenocarcinoma.

5. References:

6. Inventory Category:

• Primary: Methods
• Secondary:

7. Inventory Subcategory:

• Primary: Sentinel Species
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Mammal
  • Rat
• Study Type:
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
  • Reproductive
• Hormonal Measures:
  • Hormone Receptors
  • Carcinogenesis
• Level Of Study:
• Chemistry Metabolism:
  • Xenobiotic Metabolism
  • Exposure Monitoring
• Life Stage:
  • Female
  • Growth
• Risk Assessment:

10. Chemical Agents:

• Dioxins
• Lead
• Ddt, Des, Genistein, Arochlor 1221, Arochlor 1254

11. Performing Institution:

• UNIVERSITY OF ALABAMA AT BIRMINGHAM

12. Contact:

Edit (password needed)