|SINGHAL, ROHIT - Arkansas Children'S Nutrition Research Center (ACNC)|
|BADGER, THOMAS - Arkansas Children'S Nutrition Research Center (ACNC)|
|RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)|
Submitted to: Society of Toxicology
Publication Type: Abstract Only
Publication Acceptance Date: 12/5/2008
Publication Date: 3/1/2009
Citation: Singhal, R., Badger, T.M., Ronis, M.J. 2009. Estrogenic status modulates the effect of soy on hepatic responses to 7,12- dimethylbenz(a)anthracene [abstract]. The Toxicologist. 108(1):347. Abstract No. 1671.
Technical Abstract: We examined the influence of estradiol (E2) status and soy protein isolate (SPI) intake on the hepatic responses altered by 7,12-dimethylbenz(a)anthracene (DMBA, a polycyclic aromatic hydrocarbon [PAH]). Sprague-Dawley rats were ovariectomized (OVX) at PND50 and infused with E2 or vehicle for 14d and gavaged with 50mg/kg DMBA or vehicle 24 h before sacrifice at PND64. Rats were fed an AIN-93G diet made with SPI or casein as sole protein source throughout the study. Basal AhR protein levels were reduced (P<0.05) by SPI feeding irrespective of the E2 status. However, DMBA increased (P<0.05) AhR-induced CYP1A1 gene expression in OVX, SPI-fed rats, but reduced (P<0.05) CYP1A1 in OVX+E2, SPI-fed rats. Chromatin-immunoprecipitation demonstrated lower (P<0.05) DMBA-mediated recruitment of estrogen receptor alpha to the CYP1A1 promoter by SPI feeding in the presence of E2, suggesting an estrogen-like action of SPI on DMBA-mediated signaling in the absence of E2. Further, microarray analysis (Rat 230-2.0 Affymetrix-GeneChip™) revealed 231 genes common to SPI + DMBA and SPI + E2 + DMBA (normalized to E2) treatments. AhR-activated genes (CYP1A1, CYP1A2, and NQO1) were down-regulated by SPI + E2 + DMBA compared to SPI + DMBA. Unique interactions among SPI, DMBA, and E2 altered the expression profile of 316 genes, not observed by either treatment alone. Our data suggest that although E2 status does not effect soy-mediated AhR degradation, it modulates the effects of soy on many genes, including CYP1A1.