In vivo and in vitro interactions of TCDD and other ligands of the Ah-receptor: effect on embryonic and fetal tissues.
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.
Hassoun
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EA
University of Baghdad, Department of Toxicology, College of Pharmacy, Iraq.
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology; D004147:Dioxins / Q000633:toxicity*; D004622:Embryo, Mammalian; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005333:Fetus; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000187:drug effects*; D013950:Thymus Gland / Q000187:drug effects*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D001564:Benzo(a)pyrene