@article {Dencker133, author = {L Dencker and E Hassoun and R d{\textquoteright}Argy and G Alm}, title = {Fetal thymus organ culture as an in vitro model for the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.}, volume = {27}, number = {1}, pages = {133--140}, year = {1985}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Fetal thymuses from C57BL/6 (B6) and DBA/2J (D2) mice from gestation day 14 or 15 were explanted and grown for 2 and 6 days in culture in the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and a number of its congeners, known ligands of the Ah receptor (Ah, designating genetic locus for aryl hydrocarbon responsiveness). TCDD and 2,3,7,8-tetrachlorodibenzofuran (TCDBF) showed the same toxicity to B6 thymuses with a 50\% inhibition of lymphoid development (EC50) at 10(-10) M concentration. 3,3{\textquoteright},4,4{\textquoteright}-Tetrachloroazoxybenzene (TCAOB) was only 2-10 times less effective, while the EC50 of 3,3{\textquoteright},4,4{\textquoteright}-tetrachlorobiphenyl (TCB) was around 10(-8) M (100 times higher than that of TCDD). TCBs with chlorine atoms in the position close to the biphenyl bridge were nontoxic even at 10(-5) M concentration. Thymuses exposed to TCDD, TCDBF, and TCAOB in vivo at teratogenic doses given to the mothers and explanted 24-48 hr later were smaller and inhibited in their early in vitro growth, but recovered slowly (less rapid for TCDD) as judged by lymphoid cell counts and [3H]thymidine incorporation. These results indicate a good correlation for this group of compounds between their activity as ligands of the Ah receptor and toxicity in vitro. Other ligands of the Ah receptor, namely 3-methylcholanthrene and beta-naphthoflavone, were inactive at the highest concentrations tested (10(-6) M). Thymuses from D2 mice, considered Ah receptor-defective, were nonsensitive to TCDD at the concentrations used (up to 3 X 10(-8) M) after 2 days in culture, indicating more than 100 times lower sensitivity as compared to B6 thymuses. After 6 days in culture, their sensitivity was however only 1 order of magnitude lower than that of B6 thymuses. Therefore "low sensitivity" of D2 thymuses may be at least partially overcome by prolonged exposure to TCDD in vitro.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/27/1/133}, eprint = {https://molpharm.aspetjournals.org/content/27/1/133.full.pdf}, journal = {Molecular Pharmacology} }