Association between the presence of the Ah receptor in embryonic murine tissues and sensitivity to TCDD‐induced cleft palate

TCDD (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin) causes a high percentage of isolated cleft palate in the fetus when administered to the pregnant dam at day 10 of gestation but only in certain strains of mice (ie, C56BL/6J (C57BL)). These strains are also known to have a specific cytosolic receptor protein ( Ah ‐receptor) in the liver for polycyclic hydrocarbons and TCDD, and respond to these compounds by increased levels of cytochrome P‐450 mediated monooxygenase activities and probably several other enzyme systems. We have shown that midgestational embryos of sensitive strains exhibit high levels of the TCDD cytosolic receptor in the maxillary processes and secondary palatal shelves prior to palate closure. Binding studies and Scatchard plot analysis revealed an apparent Kd of 1.1 nM and a B max of 32 fmole bound TCDD/mg cytosolic protein from C57BL maxillary processes on day 13 of gestation. The TCDD resistant strain, AKR/J, did not show any specific binding of TCDD. Mesenchymal cells from C57BL secondary palatal shelves retained the cytosolic receptor for TCDD when grown in culture. These results suggest that the teratogenic effects of TCDD in sensitive murine strains are dependent upon the binding of TCDD to the cytoplasmic receptor in the fetus.