Joint anti-estrogenic effects of PCP and TCDD in primary cultures of juvenile goldfish hepatocytes using vitellogenin as a biomarker

This work evaluated the joint anti-estrogenic effects of pentachlorophenol (PCP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) against 17 beta-estradiol (E2) in juvenile goldfish (Carassius auratus) hepatocyte cultures. The level of vitellogenin (VTG) as a biomarker was determined by exposing hepatocytes to individual E2, PCP and TCDD, as well as to E2 in the presence of PCP, TCDD or their mixtures of various concentrations. PCP and TCDD did not exhibit estrogenicity. Both chemicals reduced the estrogenicity of E2, indicating the anti-estrogenic effects of PCP and TCDD. Their anti-estrogenic EC50 values were calculated. The joint anti-estrogenic effects against E2 increased with increasing the PCP-to-TCDD ratio of mixture. Marking's indices were < 0, suggesting an antagonism in antiestrogenic effects between PCP and TCDD. The anti-estrogenic effects of PCP appeared to result primarily from the competitive binding to estrogen receptor. While TCDD may undergo an indirect binding process for its anti-estrogenic effects, the accurate mechanisms remain to be understood. The observed antagonism in anti-estrogenic effects resulted apparently from the mutual inhibition by PCP and TCDD. (c) 2006 Elsevier Ltd. All rights reserved.