Significance Indole-3-Carbinol has been found to elicit TCDD-like effects, acting through the AH-receptor (aryl hydrocarbon) but with a much shorter half-life. Objectives In this study, our objective is to identify and separate the long-lasting effects of AH-receptor mediated effects from an exposure to the long-acting TCDD (which has a half-life of several years), from the acute effects of I3C. Both compounds act through the same receptor, therefore we expect many, if not all of the mechanisms to be the same as what was seen from exposure to TCDD. In the first study, there were 3 treated and 3 control animals that received 20mg/kg body weight of I3C or vehicle control respectively on day 24 of their cycle by intramuscular injection. In the subsequent study of I3C, we will evaluate the effects on both pregnant and non-pregnant animals using 6 non-pregnant and 6 pregnant females respectively. Non-pregnant animals will receive their dose as was administered in the first study. Pregnant animals will receive their treatment (administered the same as non-pregnant) on gestation day 12, as was done in the TCDD study. A series of urinary and serum evaluations will be conducted to study their hormonal profiles and the incidence of early fetal loss. In addition to the endocrine profiles that will be assessed through blood and urine, serial ultrasound of the implantation site will be monitored for growth abnormalities and early fetal loss. Results In the first part of the study, results were inconclusive due to poor cyclicity in treated animals. Future Directions The additional animals that will be treated will provide a clearer understanding of the mechanisms of action of I3C , as compared with previous studies on TCDD in both pregnant and non-pregnant animals. KEYWORDS AH-receptor, cynomolgus macaque, early fetal loss, indole-3-carbinol, TCDD

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000169-37
Application #
6277895
Study Section
Project Start
1998-05-01
Project End
1999-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
37
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
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