In vivo and in vitro interactions of TCDD and other ligands of theAh-receptor: effect on embryonic and fetal tissues

Abstract

Interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and other ligands of the Ah-receptor, had been studied in vivo, in pregnant NMRI mice, and in vitro, in the fetal thymus organ culture system. Benzo(a)pyrene (BP) increased TCDD-induced fetolethality, whereas it did not affect the rate of cleft palate formation. This may indicate that the mechanism of TCDD-induced fetal death is different from that of TCDD-induced cleft palate. 2,3,7,8-Tetrachlorodibenzofuran (TCDBF) and 3,3',4,4'-tetrachloroazoxybenzene (TCAOB) were added together to the thymus organ culture, each at a concentration that caused about 25-50% lymphoid development inhibition. Such treatment resulted in an additive effect of about 75%. Similarly, when the slightly toxic beta-naphthoflavone (BN) was added together with TCDD to the same culture system, it caused a significant increase in the lymphoid inhibitory effect of the latter compound. These may all suggest a common mechanism of action for TCDD and other ligands, which may involve a direct interaction with the receptors present in the thymus.