In vitro and in vivo association of 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo[a]pyrene with the yolk-precursor protein vitellogenin

These studies investigated the association of common environmental contaminants 2,3,7,8-tetraclorodibenzo-p-dioxin (TCDD) and benzo[a]pyrene (B[a]P) with the yolk-precursor protein vitellogenin (VTG). In vitro studies with purified VTG from the channel catfish (Ictalurus punctatus) demonstrated that ³H-TCDD and ³H- B[a]P associated with VTG in a nonsaturable manner. The magnitude of this association (i.e., pmoles of radioligand/mg VTG) increased with increasing chemical concentrations until the point of chemical insolubility in the incubation medium. In vivo, time-course experiments with gravid female mummichogs (Fundulus heteroclitus) exposed to either ³H-TCDD or ¹⁴C-B[a]P revealed time- and dose-dependent changes in total serum radiochemical content. In sera from female F. heteroclitus exposed to either chemical, >80% of detected radioactivity was associated with VTG and a second chromatographic peak, a lipoprotein fraction putatively identified as high-density lipoproteins. In experiments comparing radiochemical serum compartmentalization in estrogenized (E2+) versus control male fish, the presence of VTG in E2+ males significantly altered the overall quantity and profile of serum protein-associated radiochemical. In these experiments, serum VTG was present in very large quantities (40-50% of total serum protein) and the majority (62-81% for ³H-TCDD; 56-71% for ¹⁴C-B[a]P) of radiolabeled ligand was associated with VTG. The structure of the VTG protein, combined with the apparently nonsaturable nature of the association between VTG and these lipophilic compounds, suggests a VTG-ligand association that is both nonspecific and of significant capacity. Given the central role of VTG in egg production and early-life development, these findings suggest a significant role for VTG as a vector of xenobiotic maternal transfer. This role is further supported by companion studies (this volume) that examined oocyte accumulation of TCDD and B[a]P.

Duke Scholars

Author Richard T. Di Giulio Environmental Natural Science