Effects of polychlorinated biphenyls with Ah receptor affinity on lymphoid development in the thymus and the bursa of Fabricius of chick embryos in ovo and in mouse thymus anlagen in vitro.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and its congeners bind to the Ah receptor and are known to cause thymic atrophy in most experimental animal species and also to inhibit lymphoid development in the embryonic thymus (T-cells) and in the bursa of Fabricius of chick embryos (B-cells). The coplanar polychlorinated biphenyls (PCBs) 3,3',4,4'-tetrachlorobiphenyl (TCB), 3,3',4,4',5-pentachlorobiphenyl (PeCB), and 3,3',4,4',5,5'-hexachlorobiphenyl (HCB) (relatively strong Ah receptor ligands) and the mono-ortho-chlorinated analogues of TCB and PeCB (relatively weak Ah receptor ligands) were administered to chick embryos by air chamber injection on Day 13 of incubation. The numbers of lymphoid cells (on Day 19) in the thymus and the bursa of Fabricius were lower, in a dose-dependent manner, in embryos treated with the coplanar PCBs compared with controls. Approximate ED50 values for inhibition of bursal cell development were 4 micrograms for PeCB, 50 micrograms for TCB, and 300 micrograms/kg egg for HCB. The most immunotoxic of the mono-ortho-chlorinated analogues of TCB and PeCB were about 1000 times less potent than PeCB. The in vitro effects of the PCBs were studied in organ cultures of thymi from 15-day-old mouse fetuses. The three coplanar chlorobiphenyls inhibited lymphoid development in this culture system in a dose-dependent manner. PeCB was only about 10 times less potent (EC50 approximately 2 x 10(-9) M) than than TCDD (EC50 approximately 2 x 10(-10) M), whereas HCB and TCB were about 100 times less toxic than PeCB. No inhibition of lymphoid development by the mono-ortho-chlorinated PCBs was observed using concentrations as high as 10(-6) M.
Andersson
L
L
Department of Toxicology, Uppsala University, Sweden.
Nikolaidis
E
E
Brunström
B
B
Bergman
A
A
Dencker
L
L
D000818:Animals; D002060:Bursa of Fabricius / Q000187:drug effects* / Q000196:embryology; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects; D051379:Mice; D009924:Organ Culture Techniques; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000187:drug effects; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000187:drug effects* / Q000196:embryology
D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D011078:Polychlorinated Biphenyls